Updated on 2021/10/23

写真a

 
MAEDA Yoshinobu
 
Organization
Administrative Center Director
Position
Director
External link

Degree

  • 博士(医学) ( 岡山大学 )

Research Interests

  • 造血幹細胞移植学

  • hematopoietic stem cell transplantation

Research Areas

  • Life Science / Hematology and medical oncology

Education

  • Okayama University   Medical School  

    - 1992

      More details

    Country: Japan

    researchmap

  • Okayama University    

    - 1992

      More details

Research History

  • - 岡山大学医歯薬学総合研究科 教授

    2017

      More details

  • - Professor,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2017

      More details

  • Senior Assistant Professor,University Hospital of Medicine and Dentistry,Okayama University

    2014 - 2017

      More details

  • Okayama University   Okayama University Hospital

    2014 - 2017

      More details

  • Assistant Professor,University Hospital of Medicine and Dentistry,Okayama University

    2004 - 2014

      More details

  • Okayama University   Okayama University Hospital

    2004 - 2014

      More details

  • - Assistant Professor

    2004

      More details

  • - 岡山大学 医学部・歯学部附属病院 助教

    2004

      More details

  • ミシガン大学がんセンター 未設定

    2001 - 2004

      More details

  • 愛媛県立中央病院 未設定

    2000 - 2001

      More details

  • Okayama University   Medical School

    1996 - 2000

      More details

  • 四国がんセンター 未設定

    1994 - 1996

      More details

  • 滝宮総合病院 未設定

    1993 - 1994

      More details

  • 神戸西市民病院 未設定

    1992 - 1993

      More details

  • Okayama University   Medical School

    1992

      More details

▼display all

Professional Memberships

  • 第34回 日本造血幹細胞移植学会

      More details

  • 日本造血幹細胞移植学会

      More details

  • 日本成人白血病治療共同研究グループ

      More details

  • 日本リンパ網内系学会

      More details

  • 日本血液学会

      More details

  • 日本血液学会中四国地方会

      More details

  • 日本内科学会地方会

      More details

  • 日血地方会

      More details

  • 第29回 日本造血幹細胞移植学会

      More details

  • 悪性リンパ腫治療研究会

      More details

  • 第69回 日本血液学会 第49回 日本臨床血液学会

      More details

▼display all

Committee Memberships

  • 第34回 日本造血幹細胞移植学会   教育講演  

    2011   

      More details

    Committee type:Academic society

    第34回 日本造血幹細胞移植学会

    researchmap

  • 日本リンパ網内系学会   将来構想実施委員、学術・企画委員、保険診療委員  

    2011   

      More details

    Committee type:Academic society

    日本リンパ網内系学会

    researchmap

  • 日本血液学会   代議員  

    2009   

      More details

    Committee type:Academic society

    日本血液学会

    researchmap

  • 日本内科学会地方会   評議員  

    2009   

      More details

    Committee type:Academic society

    日本内科学会地方会

    researchmap

  • 日本造血幹細胞移植学会   臨床研究委員、HLA-WG委員  

    2009   

      More details

    Committee type:Academic society

    日本造血幹細胞移植学会

    researchmap

  • 日本血液学会   座長  

    2009   

      More details

    Committee type:Academic society

    日本血液学会

    researchmap

  • 日本内科学会地方会   座長  

    2009   

      More details

    Committee type:Academic society

    日本内科学会地方会

    researchmap

  • 日血地方会   座長  

    2008   

      More details

    Committee type:Academic society

    日血地方会

    researchmap

  • 悪性リンパ腫治療研究会   座長  

    2008   

      More details

    Committee type:Academic society

    悪性リンパ腫治療研究会

    researchmap

  • 悪性リンパ腫治療研究会   幹事  

    2008   

      More details

    Committee type:Academic society

    悪性リンパ腫治療研究会

    researchmap

  • 第69回 日本血液学会 第49回 日本臨床血液学会   シンポジスト  

    2007   

      More details

    Committee type:Academic society

    第69回 日本血液学会 第49回 日本臨床血液学会

    researchmap

  • 第29回 日本造血幹細胞移植学会   シンポジスト  

    2006   

      More details

    Committee type:Academic society

    第29回 日本造血幹細胞移植学会

    researchmap

  • 日本成人白血病治療共同研究グループ   プロトコール委員  

    2005   

      More details

    Committee type:Academic society

    日本成人白血病治療共同研究グループ

    researchmap

  • 日本血液学会中四国地方会   評議員  

    2005   

      More details

    Committee type:Academic society

    日本血液学会中四国地方会

    researchmap

▼display all

 

Books

  • 症例から学ぶ造血幹細胞移植

    2009 

     More details

MISC

  • Characteristic Distribution Pattern of CD30-positive Cytotoxic T Cells Aids Diagnosis of Kikuchi-Fujimoto Disease

    Tetsuya Tabata, Katsuyoshi Takata, Tomoko Miyata-Takata, Yasuharu Sato, Shin Ishizawa, Tomoyoshi Kunitomo, Keina Nagakita, Nobuhiko Ohnishi, Kohei Taniguchi, Mai Noujima-Harada, Yoshinobu Maeda, Mitsune Tanimoto, Tadashi Yoshino

    Applied Immunohistochemistry and Molecular Morphology   26 ( 4 )   274 - 282   2018

     More details

    Language:English   Publisher:Lippincott Williams and Wilkins  

    Introduction: Histiocytic necrotizing lymphadenitis (or Kikuchi-Fujimoto disease) frequently occurs in Asian young adult females and typically presents as cervical lymphadenopathy with unknown etiology. Although large immunoblasts frequently appear in Kikuchi-Fujimoto disease, the diffuse infiltration of these cells can cause difficulty in establishing a differential diagnosis from lymphoma. In such cases, CD30 immunostaining may be used
    however, the extent or distribution pattern of CD30-positive cells in Kikuchi-Fujimoto disease remains largely unknown. Here we investigated the expression of CD30 and its clinicopathologic significance. Materials and Methods: We investigated 30 Kikuchi-Fujimoto disease and 16 control [6, systemic lupus erythematosus (SLE)
    10, reactive lymphoid hyperplasia (RLH)] cases. Results: The number of CD30-positive cells in Kikuchi-Fujimoto disease was significantly more than that in SLE and RLH, and majority of these cells were located around necrotic areas. Moreover, double immunohistochemical staining showed these CD30-positive cells to be CD8-positive cytotoxic T cells, suggesting that activated cytotoxic T cells around necrotic areas are a characteristic feature of this disease. Clinicopathologic analysis showed that cases with abundant CD30-positive cells were predominantly female with only mild symptoms and normal laboratory data. Conclusions: In Kikuchi-Fujimoto disease cases, CD30-positive cytotoxic T cells were abundant around necrotic areas
    this histologic feature may be helpful to differentiate this disease from SLE and RLH.

    DOI: 10.1097/PAI.0000000000000411

    Scopus

    researchmap

  • Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707

    Yoshinobu Maeda, Hisakazu Nishimori, Isao Yoshida, Yasushi Hiramatsu, Masatoshi Uno, Yasufumi Masaki, Kazutaka Sunami, Taro Masunari, Yuichiro Nawa, Hiromichi Yamane, Hiroshi Gomyo, Tsutomu Takahashi, Tomofumi Yano, Keitaro Matsuo, Koichi Ohshima, Shigeo Nakamura, Tadashi Yoshino, Mitsune Tanimoto

    HAEMATOLOGICA   102 ( 12 )   2097 - 2103   2017.12

     More details

    Language:English   Publisher:FERRATA STORTI FOUNDATION  

    The standard CHOP therapy for peripheral T-cell lymphoma has resulted in unsatisfactory outcomes and it is still not clear what is the optimal front-line therapy. We conducted a multicenter phase II study of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone (EPOCH) for untreated peripheral T-cell lymphoma patients. In this prospective study, 41 patients were treated with dose-adjusted-EPOCH as initial therapy: peripheral T-cell lymphoma-not otherwise specified, n=21; angioimmunoblastic T-cell lymphoma, n=17; anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, n=2; and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, n=1. Median patient age was 64 years (range: 3279 years). According to the International Prognostic Index criteria, 51.2% were at high-intermediate or high risk. The overall response and complete response rates were 78.0% [95% confidence interval (CI): 62.4-89.4%] and 61.0% (95% CI: 44.5-75.8%), respectively. At the median follow up of 24.0 months, the 2-year progression-free survival and overall survival were 53.3% (95% CI: 36.4-67.5%) and 73.2% (95% CI: 56.8-84.1%), respectively. The younger patients (<= 60 years old) had a high response rate (overall response 94.1% and complete response 70.6%) and survival rate (progression-free survival 62.5% and overall survival 82.4%). The most common grade >= 3 adverse events were neutropenia (74.5%), anemia (40.8%), thrombocytopenia (22.0%), and febrile neutropenia (9.0%). Dose-adjusted-EPOCH had a high response rate with a tolerable toxicity profile. Our results indicate that dose-adjusted-EPOCH is a reasonable first-line approach for peripheral T-cell lymphoma patients and may improve outcomes.

    DOI: 10.3324/haematol.2017.167742

    Web of Science

    researchmap

  • Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707

    Yoshinobu Maeda, Hisakazu Nishimori, Isao Yoshida, Yasushi Hiramatsu, Masatoshi Uno, Yasufumi Masaki, Kazutaka Sunami, Taro Masunari, Yuichiro Nawa, Hiromichi Yamane, Hiroshi Gomyo, Tsutomu Takahashi, Tomofumi Yano, Keitaro Matsuo, Koichi Ohshima, Shigeo Nakamura, Tadashi Yoshino, Mitsune Tanimoto

    HAEMATOLOGICA   102 ( 12 )   2097 - 2103   2017.12

     More details

    Language:English   Publisher:FERRATA STORTI FOUNDATION  

    The standard CHOP therapy for peripheral T-cell lymphoma has resulted in unsatisfactory outcomes and it is still not clear what is the optimal front-line therapy. We conducted a multicenter phase II study of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone (EPOCH) for untreated peripheral T-cell lymphoma patients. In this prospective study, 41 patients were treated with dose-adjusted-EPOCH as initial therapy: peripheral T-cell lymphoma-not otherwise specified, n=21; angioimmunoblastic T-cell lymphoma, n=17; anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, n=2; and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, n=1. Median patient age was 64 years (range: 3279 years). According to the International Prognostic Index criteria, 51.2% were at high-intermediate or high risk. The overall response and complete response rates were 78.0% [95% confidence interval (CI): 62.4-89.4%] and 61.0% (95% CI: 44.5-75.8%), respectively. At the median follow up of 24.0 months, the 2-year progression-free survival and overall survival were 53.3% (95% CI: 36.4-67.5%) and 73.2% (95% CI: 56.8-84.1%), respectively. The younger patients (<= 60 years old) had a high response rate (overall response 94.1% and complete response 70.6%) and survival rate (progression-free survival 62.5% and overall survival 82.4%). The most common grade >= 3 adverse events were neutropenia (74.5%), anemia (40.8%), thrombocytopenia (22.0%), and febrile neutropenia (9.0%). Dose-adjusted-EPOCH had a high response rate with a tolerable toxicity profile. Our results indicate that dose-adjusted-EPOCH is a reasonable first-line approach for peripheral T-cell lymphoma patients and may improve outcomes.

    DOI: 10.3324/haematol.2017.167742

    Web of Science

    researchmap

  • Phase II study of intrabone single unit cord blood transplantation for hematological malignancies

    Makoto Murata, Yoshinobu Maeda, Masayoshi Masuko, Yasushi Onishi, Tomoyuki Endo, Seitaro Terakura, Yuichi Ishikawa, Chisako Iriyama, Yoko Ushijima, Tatsunori Goto, Nobuharu Fujii, Mitsune Tanimoto, Hironori Kobayashi, Yasuhiko Shibasaki, Noriko Fukuhara, Yoshihiro Inamoto, Ritsuro Suzuki, Yoshihisa Kodera, Tadashi Matsushita, Hitoshi Kiyoi, Tomoki Naoe, Tetsuya Nishida

    CANCER SCIENCE   108 ( 8 )   1634 - 1639   2017.8

     More details

    Language:English   Publisher:WILEY  

    The outcomes of cord blood transplantation with non-irradiated reduced-intensity conditioning for hematological malignancies need to be improved because of graft failure and delayed engraftment. Intrabone infusion of cord blood cells has the potential to resolve the problems. In this phase II study, 21 adult patients with hematological malignancy received intrabone transplantation of serological HLA-A, B, and DR >= 4/6 matched single cord blood with a median number of cryopreserved total nucleated cells of 2.7 x 10(7) /kg (range, 2.0-4.9 x 10(7) /kg) following non-irradiated fludarabine-based reduced-intensity conditioning. Short-term methotrexate and tacrolimus were given as graft-versus-host disease prophylaxis, and granulocyte colony-stimulating factor was given after transplantation. No severe adverse events related to intrabone injection were observed. The cumulative incidences of neutrophils >= 0.5 x 10(9) /L, reticulocytes >= 1%, and platelets >= 20 x 10(9) /L recoveries were 76.2%, 71.4%, and 76.2%, respectively, with median time to recoveries of 17, 28, and 32 days after transplantation, respectively. The probability of survival with neutrophil engraftment on day 60 was 71.4%, and overall survival at 1 year after transplantation was 52.4%. The incidences of grade II-IV and III-IV acute graft-versus-host disease were 44% and 19%, respectively, with no cases of chronic graft-versus-host disease. The present study showed the safety of direct intrabone infusion of cord blood. Further analysis is required to confirm the efficacy of intrabone single cord blood transplantation with non-irradiated reduced-intensity conditioning for adult patients with hematological malignancy. This study was registered with UMIN-CTR, number 000000865.

    DOI: 10.1111/cas.13291

    Web of Science

    researchmap

  • Phase II study of intrabone single unit cord blood transplantation for hematological malignancies

    Makoto Murata, Yoshinobu Maeda, Masayoshi Masuko, Yasushi Onishi, Tomoyuki Endo, Seitaro Terakura, Yuichi Ishikawa, Chisako Iriyama, Yoko Ushijima, Tatsunori Goto, Nobuharu Fujii, Mitsune Tanimoto, Hironori Kobayashi, Yasuhiko Shibasaki, Noriko Fukuhara, Yoshihiro Inamoto, Ritsuro Suzuki, Yoshihisa Kodera, Tadashi Matsushita, Hitoshi Kiyoi, Tomoki Naoe, Tetsuya Nishida

    CANCER SCIENCE   108 ( 8 )   1634 - 1639   2017.8

     More details

    Language:English   Publisher:WILEY  

    The outcomes of cord blood transplantation with non-irradiated reduced-intensity conditioning for hematological malignancies need to be improved because of graft failure and delayed engraftment. Intrabone infusion of cord blood cells has the potential to resolve the problems. In this phase II study, 21 adult patients with hematological malignancy received intrabone transplantation of serological HLA-A, B, and DR >= 4/6 matched single cord blood with a median number of cryopreserved total nucleated cells of 2.7 x 10(7) /kg (range, 2.0-4.9 x 10(7) /kg) following non-irradiated fludarabine-based reduced-intensity conditioning. Short-term methotrexate and tacrolimus were given as graft-versus-host disease prophylaxis, and granulocyte colony-stimulating factor was given after transplantation. No severe adverse events related to intrabone injection were observed. The cumulative incidences of neutrophils >= 0.5 x 10(9) /L, reticulocytes >= 1%, and platelets >= 20 x 10(9) /L recoveries were 76.2%, 71.4%, and 76.2%, respectively, with median time to recoveries of 17, 28, and 32 days after transplantation, respectively. The probability of survival with neutrophil engraftment on day 60 was 71.4%, and overall survival at 1 year after transplantation was 52.4%. The incidences of grade II-IV and III-IV acute graft-versus-host disease were 44% and 19%, respectively, with no cases of chronic graft-versus-host disease. The present study showed the safety of direct intrabone infusion of cord blood. Further analysis is required to confirm the efficacy of intrabone single cord blood transplantation with non-irradiated reduced-intensity conditioning for adult patients with hematological malignancy. This study was registered with UMIN-CTR, number 000000865.

    DOI: 10.1111/cas.13291

    Web of Science

    researchmap

  • Clinicopathological analysis of primary central nervous system NK/T cell lymphoma: rare and localized aggressive tumour among extranasal NK/T cell tumours

    Tomoko Miyata-Takata, Katsuyoshi Takata, Seiichi Kato, Lei-Ming Hu, Mai Noujima-Harada, Shih-Sung Chuang, Yasuharu Sato, Yoshinobu Maeda, Tadashi Yoshino

    HISTOPATHOLOGY   71 ( 2 )   287 - 295   2017.8

     More details

    Language:English   Publisher:WILEY  

    AimsThe central nervous system (CNS) is a rare primary site of non-Hodgkin lymphoma. Although direct invasion of nasal natural killer (NK)/T cell tumours into CNS is reported occasionally, primary CNS NK/T cell lymphoma is extremely rare, and the clinicopathological features of primary CNS NK/T cell lymphoma remain largely unknown.
    Methods and resultsWe identified four cases from our consultation files and analysed the clinicopathological features. Three were immunocompetent and one was immunosuppressed. There were three males and one female and their ages ranged from 21 to 77 years (median: 46 years). Radiotherapy was rendered for all patients, and methotrexate was administered to two patients. The overall survival was 4-29 months (median, 19 months) for the three immunocompetent patients. Neoplastic cells exhibited medium to large atypical nuclei. Angiocentric growth and necrosis were observed. The immunophenotype was typical of NK cell tumours: CD3 epsilon, 100%; CD56, 67%; CD5, 50%; cytotoxic molecules, 100%; Epstein-Barr virus encoded small RNA (EBER), 100% and T cell receptor (TCR)- or , 0%. No TCR-gene rearrangements were detected. Reviewing 10 additional cases from the literature and comparing with extranasal NK/T cell lymphoma of the more frequent origins (skin or gastrointestinal tract), primary CNS NK/T cell lymphoma was diagnosed at an earlier stage without B symptoms but exhibited aggressive clinical behaviours.
    ConclusionsAlthough extremely rare, primary CNS NK/T cell lymphoma does occur and should always be included in the differential diagnosis and we should apply relevant markers routinely in conjunction with exploring the patient background. The accumulation of cases is indispensable to establish an effective treatment strategy for this rare and aggressive malignancy.

    DOI: 10.1111/his.13223

    Web of Science

    researchmap

  • PD-1 modulates regulatory T-cell homeostasis during low-dose interleukin-2 therapy

    Takeru Asano, Yusuke Meguri, Takanori Yoshioka, Yuriko Kishi, Miki Iwamoto, Makoto Nakamura, Yasuhisa Sando, Hideo Yagita, John Koreth, Haesook T. Kim, Edwin P. Alyea, Philippe Armand, Corey S. Cutler, Vincent T. Ho, Joseph H. Antin, Robert J. Soiffer, Yoshinobu Maeda, Mitsune Tanimoto, Jerome Ritz, Ken-ichi Matsuoka

    BLOOD   129 ( 15 )   2186 - 2197   2017.4

     More details

    Language:English   Publisher:AMER SOC HEMATOLOGY  

    CD4(+) Foxp3(+) regulatory T cells (Tregs) play a central role in the maintenance of immune tolerance after hematopoietic stem cell transplantation. We previously reported that low-dose interleukin-2 (IL-2) therapy increased circulating Tregs and improved clinical symptoms of chronic graft-versus-host-disease (cGVHD); however, the mechanisms that regulate Treg homeostasis during IL-2 therapy have not been well studied. To elucidate these regulatory mechanisms, we examined the role of inhibitory coreceptors on Tregs during IL-2 therapy in a murine model and in patients with cGVHD. Murine studies demonstrated that low-dose IL-2 selectively increased Tregs and simultaneously enhanced the expression of programmed cell death 1 (PD-1), especially on CD44(+) CD62L(+) central-memory Tregs, whereas expression of other inhibitory molecules, including CTLA-4, LAG-3, and TIM-3 remained stable. PD-1-deficient Tregs showed rapid Stat5 phosphorylation and proliferation soon after IL-2 initiation, but thereafter Tregs became proapoptotic with higher Fas and lower Bcl-2 expression. As a result, the positive impact of IL-2 on Tregs was completely abolished, and Treg levels returned to baseline despite continued IL-2 administration. We also examined circulating Tregs from patients with cGVHD who were receiving low-dose IL-2 and found that IL-2-induced Treg proliferation was promptly followed by increased PD-1 expression on central-memory Tregs. Notably, clinical improvement of GVHD was associated with increased levels of PD-1 on Tregs, suggesting that the PD-1 pathway supports Treg-mediated tolerance. These studies indicate that PD-1 is a critical homeostatic regulator for Tregs by modulating proliferation and apoptosis during IL-2 therapy. Our findings will facilitate the development of therapeutic strategies that modulate Treg homeostasis to promote immune tolerance.

    DOI: 10.1182/blood-2016-09-741629

    Web of Science

    researchmap

  • Graft-versus-leukemia effect with a WT1-specific T-cell response induced by azacitidine and donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation

    Tatsunori Ishikawa, Nobuharu Fujii, Masahide Imada, Michinori Aoe, Yusuke Meguri, Tomoko Inomata, Hiromi Nakashimai, Keiko Fujii, Shohei Yoshida, Hisakazu Nishimori, Ken-Ichi Matsuoka, Eisei Kondo, Yoshinobu Maeda, Mitsune Tanimoto

    CYTOTHERAPY   19 ( 4 )   514 - 520   2017.4

     More details

    Language:English   Publisher:ELSEVIER SCI LTD  

    Background. Azacitidine (Aza) and donor lymphocyte infusion (DLI) therapy has recently been reported as an effective salvage therapy for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Despite the high response rate and relatively long period of remission, most patients relapse again. The immunologic mechanism of the response and limited efficacy remain unknown. Case Report. Aza + DLI therapy was performed for a patient with therapy-related MDS (t-MDS), who had relapsed after allogeneic peripheral blood stem cell transplantation. We observed a powerful graft versus-leukemia (GVL) effect accompanied by an evident Wilms tumor antigen 1 (WT1)-specific CD8 T-cell response. Remission continued for 15 months, but finally the patient relapsed. The kinetics of the WT1-specific CD8 T cells were inversely associated with WT1 messenger RNA (mRNA), suggesting a WT1-driven GVL effect. Discussion. A difference of T-cell phenotype between the whole T cells and the WT1-specific CD8 T cells was observed. It is of note that the memory phenotype of the WT1-specific T cell was limited and decreased early. The immunoescape mechanism was partly supported by loss of the memory phenotype due to failure of expansion and differentiation. Conclusion. Our data suggested that a WT1-specific T-cell response at least partly contributes to the GVL effect induced by Aza + DLI. A strategy for maximizing and maintaining the memory phenotype of the CTL may be required for durable remission.

    DOI: 10.1016/j.jcyt.2016.12.007

    Web of Science

    researchmap

  • Graft-versus-leukemia effect with a WT1-specific T-cell response induced by azacitidine and donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation

    Tatsunori Ishikawa, Nobuharu Fujii, Masahide Imada, Michinori Aoe, Yusuke Meguri, Tomoko Inomata, Hiromi Nakashimai, Keiko Fujii, Shohei Yoshida, Hisakazu Nishimori, Ken-Ichi Matsuoka, Eisei Kondo, Yoshinobu Maeda, Mitsune Tanimoto

    CYTOTHERAPY   19 ( 4 )   514 - 520   2017.4

     More details

    Language:English   Publisher:ELSEVIER SCI LTD  

    Background. Azacitidine (Aza) and donor lymphocyte infusion (DLI) therapy has recently been reported as an effective salvage therapy for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Despite the high response rate and relatively long period of remission, most patients relapse again. The immunologic mechanism of the response and limited efficacy remain unknown. Case Report. Aza + DLI therapy was performed for a patient with therapy-related MDS (t-MDS), who had relapsed after allogeneic peripheral blood stem cell transplantation. We observed a powerful graft versus-leukemia (GVL) effect accompanied by an evident Wilms tumor antigen 1 (WT1)-specific CD8 T-cell response. Remission continued for 15 months, but finally the patient relapsed. The kinetics of the WT1-specific CD8 T cells were inversely associated with WT1 messenger RNA (mRNA), suggesting a WT1-driven GVL effect. Discussion. A difference of T-cell phenotype between the whole T cells and the WT1-specific CD8 T cells was observed. It is of note that the memory phenotype of the WT1-specific T cell was limited and decreased early. The immunoescape mechanism was partly supported by loss of the memory phenotype due to failure of expansion and differentiation. Conclusion. Our data suggested that a WT1-specific T-cell response at least partly contributes to the GVL effect induced by Aza + DLI. A strategy for maximizing and maintaining the memory phenotype of the CTL may be required for durable remission.

    DOI: 10.1016/j.jcyt.2016.12.007

    Web of Science

    researchmap

  • Graft-versus-leukemia effect with a WT1-specific T-cell response induced by azacitidine and donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation

    Tatsunori Ishikawa, Nobuharu Fujii, Masahide Imada, Michinori Aoe, Yusuke Meguri, Tomoko Inomata, Hiromi Nakashimai, Keiko Fujii, Shohei Yoshida, Hisakazu Nishimori, Ken-Ichi Matsuoka, Eisei Kondo, Yoshinobu Maeda, Mitsune Tanimoto

    CYTOTHERAPY   19 ( 4 )   514 - 520   2017.4

     More details

    Language:English   Publisher:ELSEVIER SCI LTD  

    Background. Azacitidine (Aza) and donor lymphocyte infusion (DLI) therapy has recently been reported as an effective salvage therapy for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Despite the high response rate and relatively long period of remission, most patients relapse again. The immunologic mechanism of the response and limited efficacy remain unknown. Case Report. Aza + DLI therapy was performed for a patient with therapy-related MDS (t-MDS), who had relapsed after allogeneic peripheral blood stem cell transplantation. We observed a powerful graft versus-leukemia (GVL) effect accompanied by an evident Wilms tumor antigen 1 (WT1)-specific CD8 T-cell response. Remission continued for 15 months, but finally the patient relapsed. The kinetics of the WT1-specific CD8 T cells were inversely associated with WT1 messenger RNA (mRNA), suggesting a WT1-driven GVL effect. Discussion. A difference of T-cell phenotype between the whole T cells and the WT1-specific CD8 T cells was observed. It is of note that the memory phenotype of the WT1-specific T cell was limited and decreased early. The immunoescape mechanism was partly supported by loss of the memory phenotype due to failure of expansion and differentiation. Conclusion. Our data suggested that a WT1-specific T-cell response at least partly contributes to the GVL effect induced by Aza + DLI. A strategy for maximizing and maintaining the memory phenotype of the CTL may be required for durable remission.

    DOI: 10.1016/j.jcyt.2016.12.007

    Web of Science

    researchmap

  • PD-1 modulates regulatory T-cell homeostasis during low-dose interleukin-2 therapy

    Takeru Asano, Yusuke Meguri, Takanori Yoshioka, Yuriko Kishi, Miki Iwamoto, Makoto Nakamura, Yasuhisa Sando, Hideo Yagita, John Koreth, Haesook T. Kim, Edwin P. Alyea, Philippe Armand, Corey S. Cutler, Vincent T. Ho, Joseph H. Antin, Robert J. Soiffer, Yoshinobu Maeda, Mitsune Tanimoto, Jerome Ritz, Ken-ichi Matsuoka

    BLOOD   129 ( 15 )   2186 - 2197   2017.4

     More details

    Language:English   Publisher:AMER SOC HEMATOLOGY  

    CD4(+) Foxp3(+) regulatory T cells (Tregs) play a central role in the maintenance of immune tolerance after hematopoietic stem cell transplantation. We previously reported that low-dose interleukin-2 (IL-2) therapy increased circulating Tregs and improved clinical symptoms of chronic graft-versus-host-disease (cGVHD); however, the mechanisms that regulate Treg homeostasis during IL-2 therapy have not been well studied. To elucidate these regulatory mechanisms, we examined the role of inhibitory coreceptors on Tregs during IL-2 therapy in a murine model and in patients with cGVHD. Murine studies demonstrated that low-dose IL-2 selectively increased Tregs and simultaneously enhanced the expression of programmed cell death 1 (PD-1), especially on CD44(+) CD62L(+) central-memory Tregs, whereas expression of other inhibitory molecules, including CTLA-4, LAG-3, and TIM-3 remained stable. PD-1-deficient Tregs showed rapid Stat5 phosphorylation and proliferation soon after IL-2 initiation, but thereafter Tregs became proapoptotic with higher Fas and lower Bcl-2 expression. As a result, the positive impact of IL-2 on Tregs was completely abolished, and Treg levels returned to baseline despite continued IL-2 administration. We also examined circulating Tregs from patients with cGVHD who were receiving low-dose IL-2 and found that IL-2-induced Treg proliferation was promptly followed by increased PD-1 expression on central-memory Tregs. Notably, clinical improvement of GVHD was associated with increased levels of PD-1 on Tregs, suggesting that the PD-1 pathway supports Treg-mediated tolerance. These studies indicate that PD-1 is a critical homeostatic regulator for Tregs by modulating proliferation and apoptosis during IL-2 therapy. Our findings will facilitate the development of therapeutic strategies that modulate Treg homeostasis to promote immune tolerance.

    DOI: 10.1182/blood-2016-09-741629

    Web of Science

    researchmap

  • PD-1 modulates regulatory T-cell homeostasis during low-dose interleukin-2 therapy

    Takeru Asano, Yusuke Meguri, Takanori Yoshioka, Yuriko Kishi, Miki Iwamoto, Makoto Nakamura, Yasuhisa Sando, Hideo Yagita, John Koreth, Haesook T. Kim, Edwin P. Alyea, Philippe Armand, Corey S. Cutler, Vincent T. Ho, Joseph H. Antin, Robert J. Soiffer, Yoshinobu Maeda, Mitsune Tanimoto, Jerome Ritz, Ken-ichi Matsuoka

    BLOOD   129 ( 15 )   2186 - 2197   2017.4

     More details

    Language:English   Publisher:AMER SOC HEMATOLOGY  

    CD4(+) Foxp3(+) regulatory T cells (Tregs) play a central role in the maintenance of immune tolerance after hematopoietic stem cell transplantation. We previously reported that low-dose interleukin-2 (IL-2) therapy increased circulating Tregs and improved clinical symptoms of chronic graft-versus-host-disease (cGVHD); however, the mechanisms that regulate Treg homeostasis during IL-2 therapy have not been well studied. To elucidate these regulatory mechanisms, we examined the role of inhibitory coreceptors on Tregs during IL-2 therapy in a murine model and in patients with cGVHD. Murine studies demonstrated that low-dose IL-2 selectively increased Tregs and simultaneously enhanced the expression of programmed cell death 1 (PD-1), especially on CD44(+) CD62L(+) central-memory Tregs, whereas expression of other inhibitory molecules, including CTLA-4, LAG-3, and TIM-3 remained stable. PD-1-deficient Tregs showed rapid Stat5 phosphorylation and proliferation soon after IL-2 initiation, but thereafter Tregs became proapoptotic with higher Fas and lower Bcl-2 expression. As a result, the positive impact of IL-2 on Tregs was completely abolished, and Treg levels returned to baseline despite continued IL-2 administration. We also examined circulating Tregs from patients with cGVHD who were receiving low-dose IL-2 and found that IL-2-induced Treg proliferation was promptly followed by increased PD-1 expression on central-memory Tregs. Notably, clinical improvement of GVHD was associated with increased levels of PD-1 on Tregs, suggesting that the PD-1 pathway supports Treg-mediated tolerance. These studies indicate that PD-1 is a critical homeostatic regulator for Tregs by modulating proliferation and apoptosis during IL-2 therapy. Our findings will facilitate the development of therapeutic strategies that modulate Treg homeostasis to promote immune tolerance.

    DOI: 10.1182/blood-2016-09-741629

    Web of Science

    researchmap

  • Phase II study of intrabone single unit cord blood transplantation for hematological malignancies

    Makoto Murata, Yoshinobu Maeda, Masayoshi Masuko, Yasushi Onishi, Tomoyuki Endo, Seitaro Terakura, Yuichi Ishikawa, Chisako Iriyama, Yoko Ushijima, Tatsunori Goto, Nobuharu Fujii, Mitsune Tanimoto, Hironori Kobayashi, Yasuhiko Shibasaki, Noriko Fukuhara, Yoshihiro Inamoto, Ritsuro Suzuki, Yoshihisa Kodera, Tadashi Matsushita, Hitoshi Kiyoi, Tomoki Naoe, Tetsuya Nishida

    Cancer Science, Japanese Journal of Cancer Research, Gann, The Japanese Journal of Cancer Research   202 - 16   2017

     More details

  • 慢性GVHDの予防と治療の進歩

    前田嘉信

    血液内科   72 ( 5 )   2017

     More details

  • A Host-Dependent Prognostic Model for Elderly Patients with Diffuse Large B-Cell Lymphoma

    Katsuhiro Miura, Jun Konishi, Takaaki Miyake, Masanori Makita, Atsuko Hojo, Yasufumi Masaki, Masatoshi Uno, Jun Ozaki, Chikamasa Yoshida, Daigo Niiya, Koichi Kitazume, Yoshinobu Maeda, Jun Takizawa, Rika Sakai, Tomofumi Yano, Kazuhiko Yamamoto, Kazutaka Sunami, Yasushi Hiramatsu, Kazutoshi Aoyama, Hideki Tsujimura, Jun Murakami, Yoshihiro Hatta, Masatoshi Kanno

    ONCOLOGIST   22 ( 5 )   554 - 560   2017

     More details

    Language:English   Publisher:WILEY  

    Background. Decision-making models for elderly patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) are in great demand.
    Patients and Methods. The Society of Lymphoma Treatment in Japan (SoLT-J), in collaboration with the West-Japan Hematology and Oncology Group (West-JHOG), collected and retrospectively analyzed the clinical records of >= 65-year-old patients with DLBCL treated with R-CHOP from 19 sites across Japan to build an algorithm that can stratify adherence to R-CHOP.
    Results. A total of 836 patients with a median age of 74 years ( range, 65-96 years) were analyzed. In the SoLT-J cohort (n=555), age >75 years, serum albumin level <3.7 g/dL, and Charlson Comorbidity Index score >= 3 were independent adverse risk factors and were defined as the Age, Comorbidities, and Albumin (ACA) index. Based on their ACA index score, patients were categorized into "excellent" (0 points), "good" (1 point), "moderate" (2 points), and "poor" (3 points) groups. This grouping effectively discriminated the 3-year overall survival rates, mean relative total doses (or relative dose intensity) of anthracycline and cyclophosphamide, unanticipated R-CHOP discontinuance rates, febrile neutropenia rates, and treatment-related death rates. Additionally, the ACA index showed comparable results for these clinical parameters when it was applied to the West-JHOG cohort (n5281).
    Conclusion. The ACA index has the ability to stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of elderly patients with DLBCL treated with R-CHOP.

    DOI: 10.1634/theoncologist.2016-0260

    Web of Science

    researchmap

  • A Host-Dependent Prognostic Model for Elderly Patients with Diffuse Large B-Cell Lymphoma.

    Miura K, Konishi J, Miyake T, Makita M, Hojo A, Masaki Y, Uno M, Ozaki J, Yoshida C, Niiya D, Kitazume K, Maeda Y, Takizawa J, Sakai R, Yano T, Yamamoto K, Sunami K, Hiramatsu Y, Aoyama K, Tsujimura H, Murakami J, Hatta Y, Kanno M

    Oncologist   0 ( 0 )   0-0   2017

     More details

  • New immunotherapy-based approach in allogeneic hematopoietic stem cell transplantation

    Yoshinobu Maeda

    International Journal of Hematology, Nippon Ketsueki Gakkai zasshi : journal of Japan Haematological Society, Acta Haematologica Japonica   1027 - 1053   2017

  • A Host-Dependent Prognostic Model for Elderly Patients with Diffuse Large B-Cell Lymphoma

    Katsuhiro Miura, Jun Konishi, Takaaki Miyake, Masanori Makita, Atsuko Hojo, Yasufumi Masaki, Masatoshi Uno, Jun Ozaki, Chikamasa Yoshida, Daigo Niiya, Koichi Kitazume, Yoshinobu Maeda, Jun Takizawa, Rika Sakai, Tomofumi Yano, Kazuhiko Yamamoto, Kazutaka Sunami, Yasushi Hiramatsu, Kazutoshi Aoyama, Hideki Tsujimura, Jun Murakami, Yoshihiro Hatta, Masatoshi Kanno

    ONCOLOGIST   22 ( 5 )   554 - 560   2017

     More details

    Language:English   Publisher:WILEY  

    Background. Decision-making models for elderly patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) are in great demand.
    Patients and Methods. The Society of Lymphoma Treatment in Japan (SoLT-J), in collaboration with the West-Japan Hematology and Oncology Group (West-JHOG), collected and retrospectively analyzed the clinical records of >= 65-year-old patients with DLBCL treated with R-CHOP from 19 sites across Japan to build an algorithm that can stratify adherence to R-CHOP.
    Results. A total of 836 patients with a median age of 74 years ( range, 65-96 years) were analyzed. In the SoLT-J cohort (n=555), age >75 years, serum albumin level <3.7 g/dL, and Charlson Comorbidity Index score >= 3 were independent adverse risk factors and were defined as the Age, Comorbidities, and Albumin (ACA) index. Based on their ACA index score, patients were categorized into "excellent" (0 points), "good" (1 point), "moderate" (2 points), and "poor" (3 points) groups. This grouping effectively discriminated the 3-year overall survival rates, mean relative total doses (or relative dose intensity) of anthracycline and cyclophosphamide, unanticipated R-CHOP discontinuance rates, febrile neutropenia rates, and treatment-related death rates. Additionally, the ACA index showed comparable results for these clinical parameters when it was applied to the West-JHOG cohort (n5281).
    Conclusion. The ACA index has the ability to stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of elderly patients with DLBCL treated with R-CHOP.

    DOI: 10.1634/theoncologist.2016-0260

    Web of Science

    researchmap

  • Phase I/II study of pralatrexate in Japanese patients with relapsed or refractory peripheral T-cell lymphoma

    Dai Maruyama, Hirokazu Nagai, Yoshinobu Maeda, Takahiko Nakane, Tatsu Shimoyama, Tomonori, Nakazato,Rika Sakai, Takayuki Ishikawa, Koji Izutsu, Ryuzo Ueda, Kensei Tobinai

    Cancer Science, Japanese Journal of Cancer Research, Gann, The Japanese Journal of Cancer Research   1535 - 1536   2017

     More details

  • Clinicopathological analysis of primary central nervous system NK/T-cell lymphoma: rare and localised aggressive tumour among extranasal NK/T-cell tumours.

    Miyata-Takata T, Takata K, Kato S, Hu LM, Noujima-Harada M, Chuang SS, Sato Y, Maeda Y, Yoshino T

    0 ( 0 )   0-0   2017

     More details

  • Clinicopathological analysis of primary central nervous system NK/T cell lymphoma

    Tomoko Miyata-Takata, Katsuyoshi Takata, Seiichi Kato, Lei Ming Hu, Mai Noujima-Harada, Shih Sung Chuang, Yasuharu Sato, Yoshinobu Maeda, Tadashi Yoshino

    Histopathology   518 - 525   2017

     More details

  • CD10 down expression in follicular lymphoma correlates with gastrointestinal lesion involving the stomach and large intestine

    Nobuhiko Ohnishi, Katsuyoshi Takata, Tomoko Miyata-Takata, Yasuharu Sato, Akira Tari, Yuka Gion, Mai Noujima-Harada, Kohei Taniguchi, Tetsuya Tabata, Keina Nagakita, Shizuma Omote, Hiroyuki Takahata, Masaya Iwamuro, Hiroyuki Okada, Yoshinobu Maeda, Hiroyuki Yanai, Tadashi Yoshino

    CANCER SCIENCE   107 ( 11 )   1687 - 1695   2016.11

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    Follicular lymphoma (FL) shows co-expression of B-cell lymphoma 2 (BCL2) and CD10, whereas downexpression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance. Gastrointestinal FL is a rare variant of FL, and its similarity with mucosa-associated lymphoid tissue lymphoma was reported. We investigated the clinicopathological and genetic features of CD10 downexpressed (CD10(down)) GI-FL. The diagnosis of CD10(down) FL was carried out with a combination of pathological and molecular analyses. The incidence of CD10(down) GI-FL was shown in 35/172 (20.3%) cases, which was more frequent than nodal FL (3.5%, P < 0.001). The difference was additionally significant between GI-FL and nodal FL when the analysis was confined to primary GI-FL (55.2% vs 3.5%, P < 0.001). Compared to CD10(+) GI-FL, CD10(down) GI-FL significantly involved the stomach or large intestine (P = 0.015), and additionally showed the downexpression of BCL6 (P < 0.001). The follicular dendritic cell meshwork often showed a duodenal pattern in the CD10(down) group (P = 0.12). Furthermore, a lymphoepithelial lesion was observed in 5/12 (40%) gastric FL cases, which indicated caution in the differentiation of mucosa-associated lymphoid tissue lymphoma. Molecular analyses were undertaken in seven cases of CD10(down) GI-FL, and an identical clone was found between CD10(down) follicles and CD10(+)BCL2(+) neoplastic follicles. In the diagnosis of cases with CD10(down) BCL2(+) follicles, careful examination with molecular studies should be carried out.

    DOI: 10.1111/cas.13031

    Web of Science

    researchmap

  • An Open-labeled, Multicenter Phase II Study of Tamibarotene in Patients with Steroid-refractory Chronic Graft-versus-Host Disease

    Yoshinobu Maeda, Hisakazu Nishimori, Yoshihiro Inamoto, Hirohisa Nakamae, Masashi Sawa, Yasuo Mori, Kazuteru Ohashi, Shin-Ichiro Fujiwara, Mitsune Tanimoto

    ACTA MEDICA OKAYAMA   70 ( 5 )   409 - 412   2016.10

     More details

    Language:English   Publisher:OKAYAMA UNIV MED SCHOOL  

    Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HSCT). Retinoic acid (tamibarotene) exerts multiple effects on cell differentiation and is clinically used for the treatment of acute promyelocytic leukemia. Tamibarotene down-regulates both Th1 and Th17 differentiation in donor T cells after allogeneic HSCT, resulting in attenuation of experimental chronic GVHD. Based on preclinical data, we have launched a phase II study of tamibarotene in patients with steroid-refractory chronic GVHD. This study will clarify whether tamibarotene can exert beneficial effects in patients with steroid-refractory chronic GVHD.

    DOI: 10.18926/AMO/54603

    Web of Science

    researchmap

  • A phase II study of topotecan and cisplatin with sequential thoracic radiotherapy in elderly patients with small-cell lung cancer: Okayama Lung Cancer Study Group 0102

    Toshio Kubo, Keiichi Fujiwara, Katsuyuki Hotta, Toshiaki Okada, Shoichi Kuyama, Shingo Harita, Takashi Ninomiya, Haruhito Kamei, Shinobu Hosokawa, Akihiro Bessho, Tadashi Maeda, Toshiyuki Kozuki, Nobukazu Fujimoto, Kiichiro Ninomiya, Mitsuhiro Takemoto, Susumu Kanazawa, Nagio Takigawa, Masahiro Tabata, Mitsune Tanimoto, Hiroshi Ueoka, Katsuyuki Kiura

    CANCER CHEMOTHERAPY AND PHARMACOLOGY   78 ( 4 )   769 - 774   2016.10

     More details

    Language:English   Publisher:SPRINGER  

    Purpose The treatment outcome in elderly patients with limited-disease small-cell lung cancer (LD-SCLC) remains poor. We carried out a phase II trial of split topotecan and cisplatin (TP) therapy and sequential thoracic radiotherapy for elderly LD-SCLC patients as a follow-up to our previous phase I trial.
    Methods In total, 30 patients aged 76 years or older, with untreated LD-SCLC were enrolled. Four courses of topotecan (1.0 mg/m(2), days 1-3) and cisplatin (20 mg/m(2), days 1-3) were administered, followed by thoracic radiotherapy (1.8 Gy/day, total of 45 Gy). The primary end point was the overall response rate (ORR).
    Results The trial was terminated early with 22 patients because of slow accrual. Their median age was 79 years. The median number of courses of chemotherapy administered was three, and the actual completion rate of the entire treatment course was 41 %. The ORR was 68 % with a 95 % confidence interval of 47-89 % (15/22 cases). The median progression-free survival and overall survival were 9.1 and 22.2 months, respectively. The main toxicity was myelosuppression, with grades 3-4 neutropenia (96 %), thrombocytopenia (50 %), and febrile neutropenia (32 %).
    Conclusions This regimen produced a favorable survival outcome, despite moderate-to-severe toxicity profiles. Further efforts are necessary to define an optimal regimen for elderly patients with limited SCLC.

    DOI: 10.1007/s00280-016-3135-2

    Web of Science

    researchmap

  • An Open-labeled, Multicenter Phase II Study of Tamibarotene in Patients with Steroid-refractory Chronic Graft-versus-Host Disease

    Yoshinobu Maeda, Hisakazu Nishimori, Yoshihiro Inamoto, Hirohisa Nakamae, Masashi Sawa, Yasuo Mori, Kazuteru Ohashi, Shin-Ichiro Fujiwara, Mitsune Tanimoto

    ACTA MEDICA OKAYAMA   70 ( 5 )   409 - 412   2016.10

     More details

    Language:English   Publisher:OKAYAMA UNIV MED SCHOOL  

    Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HSCT). Retinoic acid (tamibarotene) exerts multiple effects on cell differentiation and is clinically used for the treatment of acute promyelocytic leukemia. Tamibarotene down-regulates both Th1 and Th17 differentiation in donor T cells after allogeneic HSCT, resulting in attenuation of experimental chronic GVHD. Based on preclinical data, we have launched a phase II study of tamibarotene in patients with steroid-refractory chronic GVHD. This study will clarify whether tamibarotene can exert beneficial effects in patients with steroid-refractory chronic GVHD.

    DOI: 10.18926/AMO/54603

    Web of Science

    researchmap

  • Clinicopathological features of 49 primary gastrointestinal diffuse large B-cell lymphoma cases; comparison with location, cell-of-origin, and frequency of MYD88 L265P

    Keina Nagakita, Katsuyoshi Takata, Kohei Taniguchi, Tomoko Miyata-Takata, Yasuharu Sato, Akira Tari, Nobuhiko Ohnishi, Mai Noujima-Harada, Shizuma Omote, Naoya Nakamura, Masaya Iwamuro, Yoshinobu Maeda, Hiroyuki Okada, Mitsune Tanimoto, Tadashi Yoshino

    PATHOLOGY INTERNATIONAL   66 ( 8 )   444 - 452   2016.8

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    The gastrointestinal (GI) tract is the most common primary site of extranodal diffuse large B-cell lymphoma (DLBCL), with approximately one-third of extranodal DLBCL occurring in the GI tract. We investigated the clinicopathological features and immunohistochemically-assessed cell-of-origin of 49 GI DLBCL cases (stomach, 24; small intestine, 10; colon, 15) and also examined the presence of MYD88 L265P as recently this mutation has been frequently identified in ABC-like DLBCL, particularly in extranodal sites. Small intestinal DLBCL was characterized by the preponderance of women (P = 0.041) and elevated LDH (P = 0.002) and soluble interleukin-2 receptor (P = 0.033). Small intestinal DLBCL more frequently showed anemia (P = 0.031) and elevated CRP (P = 0.029) than gastric DLBCL. ABC-like phenotype was seen in 71.4 % cases (stomach, 79 %; small intestine, 70 %; colon, 60 %). MYD88 L265P was detected in 6.1 % cases; all were primary gastric DLBCL with ABC-like phenotype but had no distinct clinicopathological features. In conclusion, GI DLBCL had different clinicopathological features according to the primary site especially in the small intestine. Also, MYD88 L265P had little involvement in GI DLBCL compared with other extranodal DLBCLs, suggesting that its pathogenesis might be different from that of organs with a high frequency of MYD88 L265P.

    DOI: 10.1111/pin.12439

    Web of Science

    researchmap

  • Clinicopathological features of 49 primary gastrointestinal diffuse large B-cell lymphoma cases; comparison with location, cell-of-origin, and frequency of MYD88 L265P

    Keina Nagakita, Katsuyoshi Takata, Kohei Taniguchi, Tomoko Miyata-Takata, Yasuharu Sato, Akira Tari, Nobuhiko Ohnishi, Mai Noujima-Harada, Shizuma Omote, Naoya Nakamura, Masaya Iwamuro, Yoshinobu Maeda, Hiroyuki Okada, Mitsune Tanimoto, Tadashi Yoshino

    PATHOLOGY INTERNATIONAL   66 ( 8 )   444 - 452   2016.8

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    The gastrointestinal (GI) tract is the most common primary site of extranodal diffuse large B-cell lymphoma (DLBCL), with approximately one-third of extranodal DLBCL occurring in the GI tract. We investigated the clinicopathological features and immunohistochemically-assessed cell-of-origin of 49 GI DLBCL cases (stomach, 24; small intestine, 10; colon, 15) and also examined the presence of MYD88 L265P as recently this mutation has been frequently identified in ABC-like DLBCL, particularly in extranodal sites. Small intestinal DLBCL was characterized by the preponderance of women (P = 0.041) and elevated LDH (P = 0.002) and soluble interleukin-2 receptor (P = 0.033). Small intestinal DLBCL more frequently showed anemia (P = 0.031) and elevated CRP (P = 0.029) than gastric DLBCL. ABC-like phenotype was seen in 71.4 % cases (stomach, 79 %; small intestine, 70 %; colon, 60 %). MYD88 L265P was detected in 6.1 % cases; all were primary gastric DLBCL with ABC-like phenotype but had no distinct clinicopathological features. In conclusion, GI DLBCL had different clinicopathological features according to the primary site especially in the small intestine. Also, MYD88 L265P had little involvement in GI DLBCL compared with other extranodal DLBCLs, suggesting that its pathogenesis might be different from that of organs with a high frequency of MYD88 L265P.

    DOI: 10.1111/pin.12439

    Web of Science

    researchmap

  • Treatment of thrombotic microangiopathy after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin

    Hideaki Fujiwara, Yoshinobu Maeda, Yasuhisa Sando, Makoto Nakamura, Katsuma Tani, Tatsunori Ishikawa, Hisakazu Nishimori, Ken-Ichi Matsuoka, Nobuharu Fujii, Eisei Kondo, Mitsune Tanimoto

    TRANSFUSION   56 ( 4 )   886 - 892   2016.4

     More details

    Language:English   Publisher:WILEY  

    BACKGROUNDTransplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic stem cell transplantation (HSCT) remains a severe complication associated with underlying endothelial damage. TMA has a high mortality rate with no definite treatments and effective treatments are needed.
    STUDY DESIGN AND METHODSThe study objective was to retrospectively analyze the outcome of patients receiving recombinant human soluble thrombomodulin (rTM), which has cytoprotective effects against calcineurin inhibitor-induced endothelial cell damage, or other therapeutics for TA-TMA from 254 consecutive HSCT recipients between 2009 to 2014 at a single institution. We hypothesized that patients receiving rTM as a first-line treatment would receive a benefit.
    RESULTSSixteen patients were diagnosed as TA-TMA. Of these 16 patients, nine were treated with rTM (rTM group), and seven received treatment other than rTM (control group) as a first-line therapy. Seven of the nine patients in the rTM group recovered from TA-TMA without complications, but none in the control group recovered. The rTM group showed a significantly better overall survival after TA-TMA onset than did the control group (median, 123.0 days vs. 45.5 days, respectively; p=0.045). The cumulative incidence of acute graft-versus-host disease was the same in both groups (56% vs. 57%, respectively; p=0.52) on Day 100 after TA-TMA onset.
    CONCLUSIONThis is the first report evaluating rTM administration for TA-TMA compared with previous treatments. Our data suggests that rTM might offer a better clinical outcome in patients with TA-TMA.

    DOI: 10.1111/trf.13437

    Web of Science

    researchmap

  • Treatment of thrombotic microangiopathy after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin

    Hideaki Fujiwara, Yoshinobu Maeda, Yasuhisa Sando, Makoto Nakamura, Katsuma Tani, Tatsunori Ishikawa, Hisakazu Nishimori, Ken-Ichi Matsuoka, Nobuharu Fujii, Eisei Kondo, Mitsune Tanimoto

    TRANSFUSION   56 ( 4 )   886 - 892   2016.4

     More details

    Language:English   Publisher:WILEY  

    BACKGROUNDTransplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic stem cell transplantation (HSCT) remains a severe complication associated with underlying endothelial damage. TMA has a high mortality rate with no definite treatments and effective treatments are needed.
    STUDY DESIGN AND METHODSThe study objective was to retrospectively analyze the outcome of patients receiving recombinant human soluble thrombomodulin (rTM), which has cytoprotective effects against calcineurin inhibitor-induced endothelial cell damage, or other therapeutics for TA-TMA from 254 consecutive HSCT recipients between 2009 to 2014 at a single institution. We hypothesized that patients receiving rTM as a first-line treatment would receive a benefit.
    RESULTSSixteen patients were diagnosed as TA-TMA. Of these 16 patients, nine were treated with rTM (rTM group), and seven received treatment other than rTM (control group) as a first-line therapy. Seven of the nine patients in the rTM group recovered from TA-TMA without complications, but none in the control group recovered. The rTM group showed a significantly better overall survival after TA-TMA onset than did the control group (median, 123.0 days vs. 45.5 days, respectively; p=0.045). The cumulative incidence of acute graft-versus-host disease was the same in both groups (56% vs. 57%, respectively; p=0.52) on Day 100 after TA-TMA onset.
    CONCLUSIONThis is the first report evaluating rTM administration for TA-TMA compared with previous treatments. Our data suggests that rTM might offer a better clinical outcome in patients with TA-TMA.

    DOI: 10.1111/trf.13437

    Web of Science

    researchmap

  • Treatment of thrombotic microangiopathy after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin

    Hideaki Fujiwara, Yoshinobu Maeda, Yasuhisa Sando, Makoto Nakamura, Katsuma Tani, Tatsunori Ishikawa, Hisakazu Nishimori, Ken-Ichi Matsuoka, Nobuharu Fujii, Eisei Kondo, Mitsune Tanimoto

    TRANSFUSION   56 ( 4 )   886 - 892   2016.4

     More details

    Language:English   Publisher:WILEY  

    BACKGROUNDTransplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic stem cell transplantation (HSCT) remains a severe complication associated with underlying endothelial damage. TMA has a high mortality rate with no definite treatments and effective treatments are needed.
    STUDY DESIGN AND METHODSThe study objective was to retrospectively analyze the outcome of patients receiving recombinant human soluble thrombomodulin (rTM), which has cytoprotective effects against calcineurin inhibitor-induced endothelial cell damage, or other therapeutics for TA-TMA from 254 consecutive HSCT recipients between 2009 to 2014 at a single institution. We hypothesized that patients receiving rTM as a first-line treatment would receive a benefit.
    RESULTSSixteen patients were diagnosed as TA-TMA. Of these 16 patients, nine were treated with rTM (rTM group), and seven received treatment other than rTM (control group) as a first-line therapy. Seven of the nine patients in the rTM group recovered from TA-TMA without complications, but none in the control group recovered. The rTM group showed a significantly better overall survival after TA-TMA onset than did the control group (median, 123.0 days vs. 45.5 days, respectively; p=0.045). The cumulative incidence of acute graft-versus-host disease was the same in both groups (56% vs. 57%, respectively; p=0.52) on Day 100 after TA-TMA onset.
    CONCLUSIONThis is the first report evaluating rTM administration for TA-TMA compared with previous treatments. Our data suggests that rTM might offer a better clinical outcome in patients with TA-TMA.

    DOI: 10.1111/trf.13437

    Web of Science

    researchmap

  • Treatment of thrombotic microangiopathy after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin

    Hideaki Fujiwara, Yoshinobu Maeda, Yasuhisa Sando, Makoto Nakamura, Katsuma Tani, Tatsunori Ishikawa, Hisakazu Nishimori, Ken-Ichi Matsuoka, Nobuharu Fujii, Eisei Kondo, Mitsune Tanimoto

    TRANSFUSION   56 ( 4 )   886 - 892   2016.4

     More details

    Language:English   Publisher:WILEY  

    BACKGROUNDTransplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic stem cell transplantation (HSCT) remains a severe complication associated with underlying endothelial damage. TMA has a high mortality rate with no definite treatments and effective treatments are needed.
    STUDY DESIGN AND METHODSThe study objective was to retrospectively analyze the outcome of patients receiving recombinant human soluble thrombomodulin (rTM), which has cytoprotective effects against calcineurin inhibitor-induced endothelial cell damage, or other therapeutics for TA-TMA from 254 consecutive HSCT recipients between 2009 to 2014 at a single institution. We hypothesized that patients receiving rTM as a first-line treatment would receive a benefit.
    RESULTSSixteen patients were diagnosed as TA-TMA. Of these 16 patients, nine were treated with rTM (rTM group), and seven received treatment other than rTM (control group) as a first-line therapy. Seven of the nine patients in the rTM group recovered from TA-TMA without complications, but none in the control group recovered. The rTM group showed a significantly better overall survival after TA-TMA onset than did the control group (median, 123.0 days vs. 45.5 days, respectively; p=0.045). The cumulative incidence of acute graft-versus-host disease was the same in both groups (56% vs. 57%, respectively; p=0.52) on Day 100 after TA-TMA onset.
    CONCLUSIONThis is the first report evaluating rTM administration for TA-TMA compared with previous treatments. Our data suggests that rTM might offer a better clinical outcome in patients with TA-TMA.

    DOI: 10.1111/trf.13437

    Web of Science

    researchmap

  • Treatment of thrombotic microangiopathy after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin

    Hideaki Fujiwara, Yoshinobu Maeda, Yasuhisa Sando, Makoto Nakamura, Katsuma Tani, Tatsunori Ishikawa, Hisakazu Nishimori, Ken-Ichi Matsuoka, Nobuharu Fujii, Eisei Kondo, Mitsune Tanimoto

    TRANSFUSION   56 ( 4 )   886 - 892   2016.4

     More details

    Language:English   Publisher:WILEY  

    BACKGROUNDTransplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic stem cell transplantation (HSCT) remains a severe complication associated with underlying endothelial damage. TMA has a high mortality rate with no definite treatments and effective treatments are needed.
    STUDY DESIGN AND METHODSThe study objective was to retrospectively analyze the outcome of patients receiving recombinant human soluble thrombomodulin (rTM), which has cytoprotective effects against calcineurin inhibitor-induced endothelial cell damage, or other therapeutics for TA-TMA from 254 consecutive HSCT recipients between 2009 to 2014 at a single institution. We hypothesized that patients receiving rTM as a first-line treatment would receive a benefit.
    RESULTSSixteen patients were diagnosed as TA-TMA. Of these 16 patients, nine were treated with rTM (rTM group), and seven received treatment other than rTM (control group) as a first-line therapy. Seven of the nine patients in the rTM group recovered from TA-TMA without complications, but none in the control group recovered. The rTM group showed a significantly better overall survival after TA-TMA onset than did the control group (median, 123.0 days vs. 45.5 days, respectively; p=0.045). The cumulative incidence of acute graft-versus-host disease was the same in both groups (56% vs. 57%, respectively; p=0.52) on Day 100 after TA-TMA onset.
    CONCLUSIONThis is the first report evaluating rTM administration for TA-TMA compared with previous treatments. Our data suggests that rTM might offer a better clinical outcome in patients with TA-TMA.

    DOI: 10.1111/trf.13437

    Web of Science

    researchmap

  • Treatment of thrombotic microangiopathy after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin

    Hideaki Fujiwara, Yoshinobu Maeda, Yasuhisa Sando, Makoto Nakamura, Katsuma Tani, Tatsunori Ishikawa, Hisakazu Nishimori, Ken-Ichi Matsuoka, Nobuharu Fujii, Eisei Kondo, Mitsune Tanimoto

    TRANSFUSION   56 ( 4 )   886 - 892   2016.4

     More details

    Language:English   Publisher:WILEY  

    BACKGROUNDTransplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic stem cell transplantation (HSCT) remains a severe complication associated with underlying endothelial damage. TMA has a high mortality rate with no definite treatments and effective treatments are needed.
    STUDY DESIGN AND METHODSThe study objective was to retrospectively analyze the outcome of patients receiving recombinant human soluble thrombomodulin (rTM), which has cytoprotective effects against calcineurin inhibitor-induced endothelial cell damage, or other therapeutics for TA-TMA from 254 consecutive HSCT recipients between 2009 to 2014 at a single institution. We hypothesized that patients receiving rTM as a first-line treatment would receive a benefit.
    RESULTSSixteen patients were diagnosed as TA-TMA. Of these 16 patients, nine were treated with rTM (rTM group), and seven received treatment other than rTM (control group) as a first-line therapy. Seven of the nine patients in the rTM group recovered from TA-TMA without complications, but none in the control group recovered. The rTM group showed a significantly better overall survival after TA-TMA onset than did the control group (median, 123.0 days vs. 45.5 days, respectively; p=0.045). The cumulative incidence of acute graft-versus-host disease was the same in both groups (56% vs. 57%, respectively; p=0.52) on Day 100 after TA-TMA onset.
    CONCLUSIONThis is the first report evaluating rTM administration for TA-TMA compared with previous treatments. Our data suggests that rTM might offer a better clinical outcome in patients with TA-TMA.

    DOI: 10.1111/trf.13437

    Web of Science

    researchmap

  • Frequent MYD88 L265P and CD79B Mutations in Primary Breast Diffuse Large B-Cell Lymphoma

    Kohei Taniguchi, Katsuyoshi Takata, Shih-Sung Chuang, Tomoko Miyata-Takata, Yasuharu Sato, Akira Satou, Yuko Hashimoto, Maiko Tamura, Keina Nagakita, Nobuhiko Ohnishi, Mai Noujima-Harada, Tetsuya Tabata, Yara Yukie Kikuti, Yoshinobu Maeda, Naoya Nakamura, Mitsune Tanimoto, Tadashi Yoshino

    AMERICAN JOURNAL OF SURGICAL PATHOLOGY   40 ( 3 )   324 - 334   2016.3

     More details

    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare disease comprising < 3% of extranodal lymphomas. It frequently reveals an activated B-cell (ABC)-like phenotype. ABC-like DLBCL was reported to have gain-of-function mutations in MYD88, CD79B, CARD11, and TNFAIP3, resulting in constitutive activation of the NF kappa B pathway. Because of the rare occurrence of PB-DLBCL, the frequency of MYD88 and CD79B mutations is still unknown. We used Sanger sequencing to study these mutations from 46 breast DLBCL cases and also investigated the associated clinicopathologic factors. MYD88 L265P was confirmed by allele-specific polymerase chain reaction and compared with the Sanger sequencing results. MYD88 L265P and CD79B mutations were detected in 27/46 (58.7%) and 11/33 (33.3%) cases, respectively. Twenty-eight of 46 cases met the criteria for PB-DLBCL, and the latter 18 cases were further classified as clinical breast DLBCL (CLB-DLBCL). The frequency of MYD88 L265P and CD79B mutations was 16/28 (57.1%) and 9/23 (39.1%), respectively, in PB-DLBCL and 11/18 (61.1%) and 2/10 (20%), respectively, in CLB-DLBCL. When the cutoff value was set at Delta Ct <= 1, the result of allele-specific polymerase chain reaction for MYD88 corresponded to those of the Sanger sequence at 92.6% sensitivity and 100% specificity. According to Choi's algorithm, 16/27 (59.3%) demonstrated an ABC-like phenotype in PB-DLBCL, and 15/18 (83.3%) demonstrated an ABC-like phenotype in CLB-DLBCL. In conclusion, MYD88 L265P and CD79B mutations were frequently detected in PB-DLBCL, and they may be key molecules associated with PB-DLBCL lymphomagenesis. Further analysis will be required to clarify the mechanism of its pathogenesis.

    DOI: 10.1097/PAS.0000000000000592

    Web of Science

    researchmap

  • A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis

    Seok Jin Kim, Dok Hyun Yoon, Arnaud Jaccard, Wee Joo Chng, Soon Thye Lim, Huangming Hong, Yong Park, Kian Meng Chang, Yoshinobu Maeda, Fumihiro Ishida, Dong-Yeop Shin, Jin Seok Kim, Seong Hyun Jeong, Deok-Hwan Yang, Jae-Cheol Jo, Gyeong-Won Lee, Chul Won Choi, Won-Sik Lee, Tsai-Yun Chen, Kiyeun Kim, Sin-Ho Jung, Tohru Murayama, Yasuhiro Oki, Ranjana Advani, Francesco d'Amore, Norbert Schmitz, Cheolwon Suh, Ritsuro Suzuki, Yok Lam Kwong, Tong-Yu Lin, Won Seog Kim

    LANCET ONCOLOGY   17 ( 3 )   389 - 400   2016.3

     More details

    Language:English   Publisher:ELSEVIER SCIENCE INC  

    Background The clinical outcome of extranodal natural killer T-cell lymphoma (ENKTL) has improved substantially as a result of new treatment strategies with non-anthracycline-based chemotherapies and upfront use of concurrent chemoradiotherapy or radiotherapy. A new prognostic model based on the outcomes obtained with these contemporary treatments was warranted.
    Methods We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort.
    Findings We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group.
    Interpretation PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy.

    DOI: 10.1016/S1470-2045(15)00533-1

    Web of Science

    researchmap

  • Relationship between HMGB1 and PAI-1 after allogeneic hematopoietic stem cell transplantation

    Shosaku Nomura, Yoshinobu Maeda, Kazuyoshi Ishii, Yuta Katayama, Hideo Yagi, Naoto Fujishima, Shuichi Ota, Masato Moriyama, Takayuki Ikezoe, Yasuhiko Miyazaki, Kunio Hayashi, Shinya Fujita, Atsushi Satake, Tomoki Ito, Taiichi Kyo, Mitsune Tanimoto

    Journal of Blood Medicine   7   2016.1

     More details

    Language:English   Publisher:Dove Medical Press Ltd  

    Background: Conditioning regimens including total body irradiation (TBI) or cyclophosphamide can mobilize high-mobility group box 1 (HMGB1) to peripheral blood. Additionally, increased plasminogen activator inhibitor (PAI)-1 levels are associated with post-allogeneic hematopoietic stem cell transplantation (aHSCT). However, changes to circulating levels of HMGB1 after aHSCT are poorly understood. Materials and methods: The study cohort included 289 patients who underwent aHSCT at one of 25 institutions in Japan. We have investigated the relationship between HMGB1 and PAI-1 following aHSCT. A significant increase in HMGB1 levels occurred after conditioning treatment. Additionally, levels of HMGB1 at day 0 were significantly increased in TBI+ patients and cyclophosphamide/TBI patients. Conclusion: Our data revealed that an increased level of HMGB1 at day 0 following aHSCT correlates with increased PAI-1 after aHSCT, which is consistent with previous reports. Increased HMGB1 at day 0 after a conditioning regimen may play a role in transplantation-associated coagulopathy following aHSCT, because PAI-1 can accelerate procoagulant activity.

    DOI: 10.2147/JBM.S93008

    Scopus

    researchmap

  • Vigorous inflammatory responses in noninfectious pulmonary complication induced by donor lymphocyte infusion

    Miyuki Nishie, Nobuharu Fujii, Yusuke Mimura, Takeru Asano, Yuka Mimura-Kimura, Keisuke Aoe, Michinori Aoe, Hiromi Nakashima, Hideaki Fujiwara, Hisakazu Nishimori, Ken-Ichi Matsuoka, Eisei Kondo, Yoshinobu Maeda, Mitsune Tanimoto

    TRANSFUSION   56 ( 1 )   231 - 236   2016.1

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    BACKGROUNDDonor lymphocyte infusion (DLI) is used for treatment of hematologic malignancy relapse or mixed chimerism after allogeneic hematopoietic stem cell transplantation. Although graft-versus-host disease is well recognized as one of the adverse effects of DLI, there are limited reports on noninfectious pulmonary complications (NIPCs) after DLI.
    CASE REPORTA 55-year-old woman with acute myeloid leukemia received DLI for conversion from recipient predominant to complete donor chimerism on Day +193 after allogeneic HSCT. Eight weeks later, she complained of dyspnea with fever; chest computed tomography revealed diffuse, bilateral, ground glass opacity and reticular appearance. She was diagnosed as having NIPC based on serum and bronchoalveolar lavage fluid (BALF) findings. She was successfully treated with prednisolone (PSL) and completely recovered.
    DISCUSSIONWe analyzed the cell profile from the BALF and 27 cytokines and chemokines in the serum using the Bio-Plex platform. The cells consisted of recipient predominant macrophages and T cells. The serum cytokine and chemokine profile showed significant elevation of interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor-, macrophage inflammatory protein (MIP)-1, and MIP-1, which declined with the improvement of symptoms after initiation of PSL treatment.
    CONCLUSIONInflammatory effectors by recipient cells, rather than allogeneic responses by donor cells, played an important role in the pathogenesis of NIPCs after DLI in the present case.

    DOI: 10.1111/trf.13283

    Web of Science

    researchmap

  • Vigorous inflammatory responses in noninfectious pulmonary complication induced by donor lymphocyte infusion

    Miyuki Nishie, Nobuharu Fujii, Yusuke Mimura, Takeru Asano, Yuka Mimura-Kimura, Keisuke Aoe, Michinori Aoe, Hiromi Nakashima, Hideaki Fujiwara, Hisakazu Nishimori, Ken-Ichi Matsuoka, Eisei Kondo, Yoshinobu Maeda, Mitsune Tanimoto

    TRANSFUSION   56 ( 1 )   231 - 236   2016.1

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    BACKGROUNDDonor lymphocyte infusion (DLI) is used for treatment of hematologic malignancy relapse or mixed chimerism after allogeneic hematopoietic stem cell transplantation. Although graft-versus-host disease is well recognized as one of the adverse effects of DLI, there are limited reports on noninfectious pulmonary complications (NIPCs) after DLI.
    CASE REPORTA 55-year-old woman with acute myeloid leukemia received DLI for conversion from recipient predominant to complete donor chimerism on Day +193 after allogeneic HSCT. Eight weeks later, she complained of dyspnea with fever; chest computed tomography revealed diffuse, bilateral, ground glass opacity and reticular appearance. She was diagnosed as having NIPC based on serum and bronchoalveolar lavage fluid (BALF) findings. She was successfully treated with prednisolone (PSL) and completely recovered.
    DISCUSSIONWe analyzed the cell profile from the BALF and 27 cytokines and chemokines in the serum using the Bio-Plex platform. The cells consisted of recipient predominant macrophages and T cells. The serum cytokine and chemokine profile showed significant elevation of interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor-, macrophage inflammatory protein (MIP)-1, and MIP-1, which declined with the improvement of symptoms after initiation of PSL treatment.
    CONCLUSIONInflammatory effectors by recipient cells, rather than allogeneic responses by donor cells, played an important role in the pathogenesis of NIPCs after DLI in the present case.

    DOI: 10.1111/trf.13283

    Web of Science

    researchmap

  • Vigorous inflammatory responses in noninfectious pulmonary complication induced by donor lymphocyte infusion

    Miyuki Nishie, Nobuharu Fujii, Yusuke Mimura, Takeru Asano, Yuka Mimura-Kimura, Keisuke Aoe, Michinori Aoe, Hiromi Nakashima, Hideaki Fujiwara, Hisakazu Nishimori, Ken-Ichi Matsuoka, Eisei Kondo, Yoshinobu Maeda, Mitsune Tanimoto

    TRANSFUSION   56 ( 1 )   231 - 236   2016.1

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    BACKGROUNDDonor lymphocyte infusion (DLI) is used for treatment of hematologic malignancy relapse or mixed chimerism after allogeneic hematopoietic stem cell transplantation. Although graft-versus-host disease is well recognized as one of the adverse effects of DLI, there are limited reports on noninfectious pulmonary complications (NIPCs) after DLI.
    CASE REPORTA 55-year-old woman with acute myeloid leukemia received DLI for conversion from recipient predominant to complete donor chimerism on Day +193 after allogeneic HSCT. Eight weeks later, she complained of dyspnea with fever; chest computed tomography revealed diffuse, bilateral, ground glass opacity and reticular appearance. She was diagnosed as having NIPC based on serum and bronchoalveolar lavage fluid (BALF) findings. She was successfully treated with prednisolone (PSL) and completely recovered.
    DISCUSSIONWe analyzed the cell profile from the BALF and 27 cytokines and chemokines in the serum using the Bio-Plex platform. The cells consisted of recipient predominant macrophages and T cells. The serum cytokine and chemokine profile showed significant elevation of interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor-, macrophage inflammatory protein (MIP)-1, and MIP-1, which declined with the improvement of symptoms after initiation of PSL treatment.
    CONCLUSIONInflammatory effectors by recipient cells, rather than allogeneic responses by donor cells, played an important role in the pathogenesis of NIPCs after DLI in the present case.

    DOI: 10.1111/trf.13283

    Web of Science

    researchmap

  • Efficacy of upfront high-dose chemotherapy plus rituximab followed by autologous peripheral blood stem cell transplantation for untreated high-intermediate-, and high-risk diffuse large B-cell lymphoma

    Tohru Murayama, Takahiro Fukuda, Hirokazu Okumura, Kazutaka Sunami, Aiko Sawazaki, Yoshinobu Maeda, Hisashi Tsurumi, Naokuni Uike, Tomonori Hidaka, Yoshifusa Takatsuka, Tetsuya Eto, Hiroyuki Tsuda, Tomoaki Fujisaki, Toshihiro Miyamoto, Naoko Tsuneyoshi, Satoshi Iyama

    International Journal of Hematology, Nippon Ketsueki Gakkai zasshi : journal of Japan Haematological Society, Acta Haematologica Japonica   1 - 10   2016

  • Prognostic model for mantle cell lymphoma in the rituximab era: a nationwide study in Japan

    Dai Chihara, Naoko Asano, Ken Ohmachi, Tomohiro Kinoshita, Masataka Okamoto, Yoshinobu Maeda, Ishikazu Mizuno, Kosei Matsue, Toshiki Uchida, Hirokazu Nagai, Momoko Nishikori, Shigeo Nakamura, Michinori Ogura, Ritsuro Suzuki

    BRITISH JOURNAL OF HAEMATOLOGY   170 ( 5 )   657 - 668   2015.9

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    Mantle cell lymphoma (MCL) is essentially incurable with conventional chemotherapy. The MCL International Prognostic Index (MIPI) is a validated specific prognostic index, but was derived from patients with advanced-stage disease primarily in the pre-rituximab era. We analysed 501 MCL patients (median age, 67years; range 22-90) treated with rituximab-containing chemotherapy, and evaluated the prognostic factors adjusted by the treatment. Five-year overall survival (OS) in the low, intermediate and high MIPI groups was 74%, 70% and 35%, respectively. Additional to MIPI risk factors, multivariate analysis revealed that low serum albumin and bone-marrow involvement were also significantly associated with a poor outcome. The revised-MIPI (R-MIPI) was constructed using six factors, namely age, performance status, white blood cell count, serum lactate dehydrogenase, bone-marrow involvement and serum albumin, which is divided into four prognostic groups. Five-year OS in low, low-intermediate (L-I), high-intermediate (H-I) and high R-MIPI groups was 92%, 75%, 61% and 19%, respectively. Hazard ratio for OS of L-I, H-I and high risk to low risk patients were 54, 83 and 330, respectively. R-MIPI, a new prognostic index with easy application to the general patient population, shows promise for identifying low- and high-risk MCL patients in the rituximab era.

    DOI: 10.1111/bjh.13486

    Web of Science

    researchmap

  • Serum level of soluble interleukin-2 receptor correlates with CD25 expression in patients with T lymphoblastic lymphoma

    Tomohiro Toji, Katsuyoshi Takata, Yasuharu Sato, Tomoko Miyata-Takata, Eiko Hayashi, Toshiyuki Habara, Yoshinobu Maeda, Mitsune Tanimoto, Tadashi Yoshino

    JOURNAL OF CLINICAL PATHOLOGY   68 ( 8 )   622 - 627   2015.8

     More details

    Language:English   Publisher:BMJ PUBLISHING GROUP  

    Acute lymphoblastic leukaemia/lymphoma (ALL/LBL) is an aggressive form of non-Hodgkin's lymphoma (NHL) affecting B-cells or T-cells, respectively. The serum level of soluble interleukin-2 receptor (sIL-2R) is known to reflect the immune activity and tumour volume in aggressive NHL; however, the release of sIL-2R in LBL has not been extensively studied. Further, the relationship between sIL-2R release and the expression level of IL-2R alpha subunit (CD25) remains unknown.
    In the present study, we examined the serum level of sIL-2R in 23 patients with T lymphoblactic lymphoma (T-LBL) and compared these with the levels in 20 patient with T acute lymphoblastic leukaemia (T-ALL), 40 patients with diffuse large B-cell lymphoma (DLBCL) and 40 patients with peripheral T-cell lymphoma (PTCL), not otherwise specified. The release of sIL-2R into the serum in patients with T-LBL was significantly lower than that for T-ALL, DLBCL and PTCL (p<0.001).
    Immunohistochemistry revealed that CD25 expression was correlated with the serum level of sIL-2R in T-LBL (p=0.0069), whereas no correlation was found to exist between serum sIL-2R levels and CD25 expression in patients with DLBCL (p=0.348) and PTCL (p=0.266). Furthermore, double immunohistochemical analysis revealed that CD25-positive cells were also found to be Foxp3-positive non-neoplastic T-cells. In conclusion, CD25-positive non-neoplastic T-cells in T-LBL are presumed to be the primary source of sIL-2R, and the low number of cells present results in a lower level of sIL-2R released into the serum compared with the other aggressive and highly aggressive lymphomas.

    DOI: 10.1136/jclinpath-2015-202934

    Web of Science

    researchmap

  • Unmanipulated Haploidentical Reduced-Intensity Stem Cell Transplantation Using Fludarabine, Busulfan, Low-Dose Antithymocyte Globulin, and Steroids for Patients in Non-Complete Remission or at High Risk of Relapse: A Prospective Multicenter Phase I/II Study in Japan. International journal

    Kazuhiro Ikegame, Takashi Yoshida, Satoshi Yoshihara, Takashi Daimon, Hiroaki Shimizu, Yoshinobu Maeda, Yasunori Ueda, Katsuji Kaida, Shinichi Ishii, Kyoko Taniguchi, Masaya Okada, Hiroya Tamaki, Hirokazu Okumura, Hiroyasu Kaya, Toshiro Kurokawa, Yoshihisa Kodera, Shuichi Taniguchi, Yoshinobu Kanda, Hiroyasu Ogawa

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   21 ( 8 )   1495 - 505   2015.8

     More details

    Language:English  

    This prospective, multicenter phase I/II study of unmanipulated HLA-haploidentical reduced-intensity stem cell transplantation using a low dose of anti-T lymphocyte globulin (ATG) and steroid was conducted in 5 institutions in Japan. Thirty-four patients with hematologic malignancies who were in an advanced stage or at a high risk of relapse at the time of transplantation were enrolled. Among them, 7 patients underwent transplantation as a second transplantation because of relapse after the previous allogeneic stem cell transplantation. The conditioning regimen consisted of fludarabine, busulfan, and ATG (Fresenius, 8 mg/kg), and graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methylprednisolone (1 mg/kg). All patients except 1 (97.1%) achieved donor-type engraftment. Rapid hematopoietic engraftment was achieved, with neutrophils > .5 × 10(9)/L on day 11 and platelets > 20 × 10(9)/L on day 17.5. Treatment was started for ≥grade I GVHD, and the cumulative incidences of acute grade I and grade II to IV GVHD were 27.5% and 30.7%, respectively. The incidence of chronic GVHD (extensive type) was 20%. Fourteen patients (41.2%) had a relapse. The cumulative incidence of transplantation-related mortality at 1 year after transplantation was 26.5%. The survival rate at day 100 was 88.2%. The survival rates at 1 year for patients with complete remission (CR)/chronic phase (n = 8) and non-CR (n = 26) status before transplantation were 62.5% and 42.3%, respectively. In the multivariate analysis, non-CR status before transplantation was the only factor significant prognostic factor of increased relapse (P = .0424), which tended to be associated with a lower survival rate (P = .0524). This transplantation protocol is safe and feasible, if a suitable donor is not available in a timely manner. As the main cause of death was relapse and not GVHD, more intensified conditioning or attenuation of GVHD prophylaxis and/or donor lymphocyte infusion may be desirable for patients with non-CR status.

    DOI: 10.1016/j.bbmt.2015.04.012

    PubMed

    researchmap

  • alpha-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice

    Hidetaka Uryu, Daigo Hashimoto, Koji Kato, Eiko Hayase, Satomi Matsuoka, Reiki Ogasawara, Shuichiro Takahashi, Yoshinobu Maeda, Hiromi Iwasaki, Toshihiro Miyamoto, Shinobu Saijo, Yoichiro Iwakura, Geoffrey R. Hill, Koichi Akashi, Takanori Teshima

    BLOOD   125 ( 19 )   3014 - 3023   2015.5

     More details

    Language:English   Publisher:AMER SOC HEMATOLOGY  

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for various hematopoietic disorders. Graft-versus-host disease (GVHD) and infections are the major obstacles of HSCT, and their close relationship has been suggested. Although roles of bacterial and viral infections in the pathophysiology of GVHD are well described, impacts of fungal infection on GVHD remain to be elucidated. In mouse models of GVHD, injection of a-mannan (Mn), a major component of fungal cell wall, or heat-killed Candida albicans exacerbated GVHD, particularly in the lung. Mn-induced donor T-cell polarization toward Th17 and lung-specific chemokine environment in GVHD led to accumulation of Th17 cells in the lung. The detrimental effects of Mn on GVHD depended on donor IL-17A production and host C-type lectin receptor Dectin-2. These results suggest a previously unrecognized link between pulmonary GVHD and fungal infection after allogeneic HSCT.

    DOI: 10.1182/blood-2014-12-615781

    Web of Science

    researchmap

  • Anti-IL-12/23 p40 Antibody Attenuates Experimental Chronic Graft-versus-Host Disease via Suppression of IFN-gamma/IL-17-Producing Cells

    Sachiyo Okamoto, Hideaki Fujiwara, Hisakazu Nishimori, Ken-ichi Matsuoka, Nobuharu Fujii, Eisei Kondo, Takehiro Tanaka, Akihiko Yoshimura, Mitsune Tanimoto, Yoshinobu Maeda

    JOURNAL OF IMMUNOLOGY   194 ( 3 )   1357 - 1363   2015.2

     More details

    Language:English   Publisher:AMER ASSOC IMMUNOLOGISTS  

    Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation. Recently, in addition to Th2 cells, Th1 and Th17 cells have been shown to contribute to chronic GVHD progression. IL-12 induces Th1 cells and IL-23 plays a role in stabilizing and/or amplifying Th17 cells, as well as in inducing IFN-gamma/IL-17 double-producing cells. Because mAb targeting the p40 subunit common to both IL-12 and IL-23 can inhibit both IL-12R and IL-23R-mediated signaling, we investigated the effects of anti-p40 mAb on a well-defined chronic GVHD mice model. Treatment of anti-p40 mAb in allogeneic recipients significantly reduced the severity of clinical and pathological chronic GVHD. Intracellular staining revealed that IFN-gamma single-positive (IL-17(-)) and IFN-gamma/IL-17 double-positive cells were suppressed in anti-p40 mAb-treated allogeneic recipients compared with control recipients. The cytokine levels of IFN-gamma and IL-17 were also decreased in serum from anti-p40 mAb-treated allogeneic recipients. T-bet expression of donor IL-17(+) CD4(+) T cells was reduced significantly in anti-p40 mAb-treated recipients, and this reduction in T-bet expression was associated with IL-22 production by donor T cells. These results suggested that anti-p40 mAb attenuated chronic GVHD via suppression of IFN-gamma/IL-17-producing cells, and that targeting the IL-12/IL-23 pathway may represent a promising therapeutic strategy for preventing and treating chronic GVHD.

    DOI: 10.4049/jimmunol.1400973

    Web of Science

    researchmap

  • t(14;16)-positive multiple myeloma shows negativity for CD56 expression and unfavorable outcome even in the era of novel drugs

    T. Narita, A. Inagaki, T. Kobayashi, Y. Kuroda, T. Fukushima, M. Nezu, S. Fuchida, H. Sakai, N. Sekiguchi, I. Sugiura, Y. Maeda, H. Takamatsu, N. Tsukamoto, D. Maruyama, Y. Kubota, M. Kojima, K. Sunami, T. Ono, M. Ri, K. Tobinai, S. Iida

    BLOOD CANCER JOURNAL   5   2015.2

     More details

    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    DOI: 10.1038/bcj.2015.6

    Web of Science

    researchmap

  • AMLの寛解導入療法におけるGOの動向は?

    前田嘉信

    中外医学社   49 - 52   2015

     More details

  • nonAPLに対してIDR(DNR)+Ara-Cを超える寛解導入療法は?

    前田嘉信

    中外医学社   45 - 48   2015

     More details

  • Primary Duodenal Follicular Lymphoma Treated With Rituximab Monotherapy and Followed-up for 15 Years.

    Seki A, Iwamuro M, Yoshioka, M, Fujii N, Okada H, Nose S, Takata K, Yoshino T, Yamamoto K

    Acta Medica Okayama   69 ( 5 )   2015

     More details

  • 多発転移に伴い血小板減少を合併した頭部血管肉腫の1例

    瀧口 徹也, 山崎 修, 牧野 麻貴, 佐伯 恭昌, 藤井 伸治, 濱田 和俊, 岩月 啓氏

    Skin Cancer   29 ( 3 )   2015

  • ICU管理が必要であったMulticentric Castleman Disease(MCD)/TAFRO症候群(1)

    近藤 英生, 佐藤 康晴, 浅野 豪, 花山 宜久, 木村 耕介, 塚原 紘平, 鵜川 豊世武, 谷本 光音, 吉野 正, 大塚 文男

    日本リンパ網内系学会会誌   55115   2015

     More details

  • CNS浸潤伴う治療抵抗性ALK陽性ALCLに対しCrizotinibを使用した1例

    濱崎 豊, 石川 立則, 近藤 英生, 吉野 正, 長谷川 詠子, 瀬崎 伸夫, 藤原 英晃, 西森 久和, 松岡 賢市, 藤井 伸治, 前田 嘉信, 谷本 光音

    臨床血液   56 ( 5 )   2015

     More details

  • 肺全摘後症候群に伴う急性呼吸不全に対して胸腔内ガス注入療法が著効した1例

    妹尾 賢, 久保 寿夫, 二宮 貴一朗, 岡田 俊明, 鷲尾 一浩, 張田 信吾

    日本呼吸器学会誌   4 ( 6 )   2015

     More details

  • The impact of HLA mismatch direction on the outcome of unrelated bone marrow transplantation: A retrospective analysis from the JSHCT

    Kanda J, Ichinohe T, Fuji S, Maeda Y, Ohashi K, Fukuda T, Miyamura K, Iwato K, Eto T, Nakamae H, Kobayashi N, Mori T, Mori SI, Morishima Y, Atsuta Y, Kanda Y

    Biol Blood Marrow Transplant   21 ( 2 )   305 - 311   2015

  • 【リンパ腫学-最新の研究動向-】 リンパ腫の治療 造血幹細胞移植 自家造血幹細胞移植

    前田 嘉信

    日本臨床   73 ( 増刊8 リンパ腫学 )   2015

     More details

  • 【臨床研究中核病院から】慢性移植片対宿主病に対するタミバロテン(AM80G)の医師主導臨床第Ⅱ相試験

    西森久和, 前田嘉信

    岡山医学会雑誌   127 ( 2 )   133 - 137   2015

  • 再発・難治性ホジキンリンパ腫に対するPD-1免疫チェックポイント阻害薬ニボルマブの有効性

    前田 嘉信

    血液内科   71 ( 4 )   2015

     More details

  • Preparation of Enteric-coated Capsules of Beclomethasone Dipropionate for Patients with Intestinal Graft-versus-Host Disease and a Case Study

    Kiminaka Murakawa, Tomoaki Sato, Yoshinobu Maeda, Yoshihisa Kitamura, Mitsune Tanimoto, Toshiaki Sendo

    ACTA MEDICA OKAYAMA   67 ( 5 )   319 - 324   2013.10

     More details

    Language:English   Publisher:OKAYAMA UNIV MED SCHOOL  

    Graft-versus-host disease (GVHD) is a major concern in transplantation patients. Gut GVHD is accompanied by diarrhea, abdominal pain, and/or melena. Although oral treatment with corticosteroids (CSs) is effective in treating gut GVHD, it can cause adverse reactions that affect the entire body. Topical administration of CSs can be effective in treating diseases in which lesions are limited locally, because adverse reactions can then be alleviated. In this study, we examine and discuss an enteric-coated beclomethasone dipropionate (BDP) capsule (BDP-EC) formulated at Okayama University Hospital. The BDP-EC did not dissolve in solution 1 (pH1.2), and began disintegrating in solution 2 (pH6.8) after 5min, with a mean dissolution rate at 15min of 85%. We then used the capsule to treat a patient who developed gut GVHD after allogeneic hematopoietic stem cell transplantation. Clinically, the frequency of diarrhea decreased after BDP-EC administration. In addition, we were able to decrease the prednisolone equivalent dose. Symptoms associated with adverse reactions to BDP were not observed during the hospitalization period. These findings suggest that the administration of BDP-EC in the early stages of gut GVHD may allow a reduction in the initial doses of systemic CSs.

    DOI: 10.18926/AMO/51868

    Web of Science

    researchmap

  • B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma without mediastinal disease: mimicking nodular sclerosis classical Hodgkin lymphoma

    Noriko Iwaki, Yasuharu Sato, Toshiro Kurokawa, Yoshinobu Maeda, Kyotaro Ohno, Mai Takeuchi, Katsuyoshi Takata, Yorihisa Orita, Shinji Nakao, Tadashi Yoshino

    MEDICAL MOLECULAR MORPHOLOGY   46 ( 3 )   172 - 176   2013.9

     More details

    Language:English   Publisher:SPRINGER JAPAN KK  

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma (BCLu-DLBCL/CHL), also known as gray-zone lymphoma, has overlapping clinical and biological characteristics of both diffuse large B-cell lymphoma and classical Hodgkin lymphoma (CHL). These lymphomas are typically associated with mediastinal disease, and extranodal involvement is rare. In the present report, we describe a case of a 78-year-old woman with BCLu-DLBCL/CHL found to have extranodal lesions and no evidence of mediastinal disease. Although biopsy specimens were histologically similar to nodular sclerosis CHL, the tumor cells were positive for CD30 and mature B-cell markers, such as CD20, CD79a, PAX5, BOB.1, and OCT-2, but negative for CD15. Furthermore, the patient had extranodal lesions and an increased level of soluble IL-2 receptor. These findings are unusual in CHL. Therefore, we diagnosed the patient with BCLu-DLBCL/CHL. She received adriamycin, bleomycin, vincristine, and dacarbazine therapy and exhibited partial response. Some cases without mediastinal disease, such as our case, have been reported; however, these cases are rare and further studies are required.

    DOI: 10.1007/s00795-013-0038-8

    Web of Science

    researchmap

  • Distinct morphologic, phenotypic, and clinical-course characteristics of indolent peripheral T-cell lymphoma

    Eiko Hayashi, Katsuyoshi Takata, Yasuharu Sato, Yukie Tashiro, Yoshiro Tachiyama, Seiko Sawada-Kitamura, Yasushi Hiramatsu, Shun Sugiguchi, Soichiro Nose, Mitsuyoshi Hirokawa, Midori Ando, Lamia Abd Mader, Yoshinobu Maeda, Mitsune Tanimoto, Tadashi Yoshino

    HUMAN PATHOLOGY   44 ( 9 )   1927 - 1936   2013.9

     More details

    Language:English   Publisher:W B SAUNDERS CO-ELSEVIER INC  

    Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) consists of a heterogeneous group of lymphomas. Patients. generally show an aggressive clinical course and very poor outcome. Although the 2008 World Health Organization classification of PTCL-NOS includes 3 variants, low-grade lymphoma is not Included. Of 277 PTCL-NOS cases recorded in our consultation files, we examined the clinicopathologic characteristics of 10 patients with T-cell lymphomas composed of small-sized cells with slight nuclear atypia. Eight patients showed extranodal involvement (5 patients, spleen; 3 patients, thyroid), and 5 patients were at clinical stage I or II. Histologically, all samples presented diffuse infiltrate of small lymphoid cells, with few mitotic figures. Immunohistologically, all samples were positive for CD3, and CD:20 Was detected in 5 samples. All samples showed a low Ki-67 labeling index (mean, 1.05%), and 7 samples were positive for central memory T-cell markers. Clonal T-cell receptor gamma chain and/or alpha-beta chain gene rearrangements were detected in all 10 patients. Five patients received chemotherapy, whereas for 3 patients, treatment consisted only of observation following surgical resection of the spleen or thyroid. Nine patients were alive at a median follow-up time of 19.5 months, whereas 1 patient died of an unrelated disease. The present study strongly indicates that T-cell lymphoma with small-sized lymphoma cells and a low Ki-67 labeling index is a distinct variant. Recognition of this novel lymphoma subtype, which should not be defined merely as PTCL-NOS, should be seriously considered. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.humpath.2013.03.002

    Web of Science

    researchmap

  • Comparison of outcomes between autologous and allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphomas with central review of pathology

    S-W Kim, S-S Yoon, R. Suzuki, Y. Matsuno, H. G. Yi, T. Yoshida, M. Imamura, A. Wake, K. Miura, M. Hino, T. Ishikawa, J. S. Kim, Y. Maeda, J-J Lee, H. J. Kang, H. S. Lee, J-H Lee, K. Izutsu, T. Fukuda, C. W. Kim, T. Yoshino, K. Ohshima, S. Nakamura, K. Nagafuji, J. Suzumiya, M. Harada, C. S. Kim

    LEUKEMIA   27 ( 6 )   1394 - 1397   2013.6

     More details

    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    DOI: 10.1038/leu.2012.321

    Web of Science

    researchmap

  • De novo CD5-positive diffuse large B-cell lymphomas show high specificity for cyclin D2 expression

    Takuro Igawa, Yasuharu Sato, Katsuyoshi Takata, Noriko Iwaki, Takehiro Tanaka, Naoko Asano, Yoshinobu Maeda, Yorihisa Orita, Naoya Nakamura, Shigeo Nakamura, Tadashi Yoshino

    DIAGNOSTIC PATHOLOGY   8   81 - 81   2013.5

     More details

    Language:English   Publisher:BIOMED CENTRAL LTD  

    D cyclins positively regulate the cell cycle and mediate the pathogenesis of some lymphomas. Cyclin D1 overexpression is the hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 are reportedly not as specific to certain lymphomas as cyclin D1. In this study, cyclin D2 was found to be overexpressed in 98% of de novo CD5-positive diffuse large B-cell lymphomas (DLBCLs) (50/51) and in 28% of CD5-negative DLBCLs (14/51). A statistically significant difference was observed between these two groups (p<0.0001). In contrast, no statistical difference was found in the cyclin D3 expression between CD5-positive (18/51) and CD5-negative (24/51) DLBCLs (p=0.23). Based on these findings, cyclin D2 is therefore considered to be closely associated with de novo CD5-positive DLBCLs. This insight may be useful for overcoming the inferior survival of this aggressive lymphoma. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1382856320966453

    DOI: 10.1186/1746-1596-8-81

    Web of Science

    researchmap

  • Impact of a single human leucocyte antigen (HLA) allele mismatch on the outcome of unrelated bone marrow transplantation over two time periods. A retrospective analysis of 3003 patients from the HLA Working Group of the Japan Society for Blood and Marrow Transplantation

    Yoshinobu Kanda, Junya Kanda, Yoshiko Atsuta, Yoshinobu Maeda, Tatsuo Ichinohe, Kazuteru Ohashi, Takahiro Fukuda, Koichi Miyamura, Hiroatsu Iida, Takehiko Mori, Koji Iwato, Tetsuya Eto, Keisei Kawa, Satoshi Morita, Yasuo Morishima

    BRITISH JOURNAL OF HAEMATOLOGY   161 ( 4 )   566 - 577   2013.5

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    A previous Japanese study revealed that a human leucocyte antigen (HLA)-A or -B allele mismatch was associated with higher overall mortality, whereas an HLA-C or -DRB1 allele mismatch did not affect mortality after serologically matched unrelated bone marrow transplantation (BMT). This study reanalysed 3003 adult patients who underwent unrelated BMT from a serologically HLA-A, -B, or -DR matched unrelated donor between 1993 and 2009 using the latest database, that included 1966 HLA-matched unrelated BMT and 187, 31, 524, and 295 unrelated BMT with a single HLA-A, -B, -C, or -DRB1 allele mismatch, respectively. As opposed to our previous findings, HLA-C and -DRB1 mismatches had a significant negative impact [hazard ratio (HR) 1 center dot 35, P<0 center dot 001, and HR 1 center dot 45, P<0 center dot 001] on survival in the period 20002009. The negative impact of each single HLA allele mismatch was not significantly different among the HLA-A, -B, -C, and -DRB1 mismatches (P=0 center dot 79). An interaction test revealed that the effects of single HLA-C and -DRB1 allele mismatches significantly differed over the two time periods (P=0 center dot 032 and P=0 center dot 0072, respectively). In conclusion, the impact of a single HLA allele mismatch changed over time. In the recent cohort, the negative impact of HLA-DRB1 and -C mismatches became apparent.

    DOI: 10.1111/bjh.12279

    Web of Science

    researchmap

  • Antibiotic sensitivity of bacteria on the oral mucosa after hematopoietic cell transplantation

    Yoshihiko Soga, Yoshinobu Maeda, Mitsune Tanimoto, Takayuki Ebinuma, Hiroshi Maeda, Shogo Takashiba

    SUPPORTIVE CARE IN CANCER   21 ( 2 )   367 - 368   2013.2

     More details

    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:SPRINGER  

    DOI: 10.1007/s00520-012-1602-9

    Web of Science

    researchmap

  • Duodenal follicular lymphoma lacks AID but expresses BACH2 and has memory B-cell characteristics

    Katsuyoshi Takata, Yasuharu Sato, Naoya Nakamura, Mami Tokunaka, Yukari Miki, Yara Yukie Kikuti, Kazuhiko Igarashi, Etsuro Ito, Hideo Harigae, Seiichi Kato, Eiko Hayashi, Takashi Oka, Yoshinobu Hoshii, Akira Tari, Hiroyuki Okada, Abd Alkader Lamia Mohamad, Yoshinobu Maeda, Mitsune Tanimoto, Tomohiro Kinoshita, Tadashi Yoshino

    Modern Pathology   26 ( 1 )   22 - 31   2013.1

     More details

    Language:English  

    We have reported previously that duodenal follicular lymphoma (FL) is distinct from nodal FL and showed more resemblance to mucosa-associated lymphoid tissue lymphoma, and that FL frequently involved the duodenal second portion. In the present study, we examined duodenal FLs and gastric/colonic FLs to clarify the clinicopathological and immunological differences between the tumor types. We analyzed 8 samples of gastric FL, 17 of duodenal ones, and 5 of colonic/rectal ones, and characterized them by immunohistochemistry, immunogenotyping, and histology. Gastric and colonic FLs presented in submucosal to subserosal areas, whereas duodenal ones presented in the mucosal to submucosal layers. Immunohistochemical analysis revealed that duodenal FLs exhibited the following phenotypes: CD10 (+), B-cell lymphoma 2 (BCL-2) (+), BCL-6 (+), activation-induced cytidine deaminase (AID) (-), BACH2 (+), CD27 (+), MUM-1 (-), Blimp-1 (-), and loose CD21 network (duodenal pattern). Gastric/colonic FLs exhibited the following phenotypes: CD10 (+), BCL-2 (+), BCL-6 (+), AID (+), BACH2 (+), CD27 (-), MUM-1 (-), Blimp-1 (-), and a dense CD21 network (nodal pattern). Expression of AID and CD27 in lymphoma cells and the CD21 network pattern were considerably different between duodenal FLs and gastric/colonic ones. Moreover, in situ hybridization revealed that, in the duodenal FLs, BACH2 was expressed at the periphery of the tumor follicle and tumor villi. The number of immunoglobulin heavy-chain variable domains VH4 and VH5 were higher in duodenal follicular lymphomoas than in gastric FLs. The lymphoma cells of duodenal FLs are different from those of gastric/colonic FLs, and duodenal FL is distinct even within the gastrointestinal tract. Somatic hypermutation in immunoglobulin genes and CD27 expression are hallmarks of memory B cells. We suggest that duodenal FL cells are in the memory B-cell stage, and require BACH2 instead of AID for ongoing mutation. © 2013 USCAP, Inc.

    DOI: 10.1038/modpathol.2012.127

    Scopus

    PubMed

    researchmap

  • Duodenal follicular lymphoma lacks AID but expresses BACH2 and has memory B-cell characteristics

    Katsuyoshi Takata, Yasuharu Sato, Naoya Nakamura, Mami Tokunaka, Yukari Miki, Yara Yukie Kikuti, Kazuhiko Igarashi, Etsuro Ito, Hideo Harigae, Seiichi Kato, Eiko Hayashi, Takashi Oka, Yoshinobu Hoshii, Akira Tari, Hiroyuki Okada, Abd Alkader Lamia Mohamad, Yoshinobu Maeda, Mitsune Tanimoto, Tomohiro Kinoshita, Tadashi Yoshino

    Modern Pathology   26 ( 1 )   22 - 31   2013.1

     More details

    Language:English  

    We have reported previously that duodenal follicular lymphoma (FL) is distinct from nodal FL and showed more resemblance to mucosa-associated lymphoid tissue lymphoma, and that FL frequently involved the duodenal second portion. In the present study, we examined duodenal FLs and gastric/colonic FLs to clarify the clinicopathological and immunological differences between the tumor types. We analyzed 8 samples of gastric FL, 17 of duodenal ones, and 5 of colonic/rectal ones, and characterized them by immunohistochemistry, immunogenotyping, and histology. Gastric and colonic FLs presented in submucosal to subserosal areas, whereas duodenal ones presented in the mucosal to submucosal layers. Immunohistochemical analysis revealed that duodenal FLs exhibited the following phenotypes: CD10 (+), B-cell lymphoma 2 (BCL-2) (+), BCL-6 (+), activation-induced cytidine deaminase (AID) (-), BACH2 (+), CD27 (+), MUM-1 (-), Blimp-1 (-), and loose CD21 network (duodenal pattern). Gastric/colonic FLs exhibited the following phenotypes: CD10 (+), BCL-2 (+), BCL-6 (+), AID (+), BACH2 (+), CD27 (-), MUM-1 (-), Blimp-1 (-), and a dense CD21 network (nodal pattern). Expression of AID and CD27 in lymphoma cells and the CD21 network pattern were considerably different between duodenal FLs and gastric/colonic ones. Moreover, in situ hybridization revealed that, in the duodenal FLs, BACH2 was expressed at the periphery of the tumor follicle and tumor villi. The number of immunoglobulin heavy-chain variable domains VH4 and VH5 were higher in duodenal follicular lymphomoas than in gastric FLs. The lymphoma cells of duodenal FLs are different from those of gastric/colonic FLs, and duodenal FL is distinct even within the gastrointestinal tract. Somatic hypermutation in immunoglobulin genes and CD27 expression are hallmarks of memory B cells. We suggest that duodenal FL cells are in the memory B-cell stage, and require BACH2 instead of AID for ongoing mutation. © 2013 USCAP, Inc.

    DOI: 10.1038/modpathol.2012.127

    Scopus

    PubMed

    researchmap

  • Association between IgG4-related disease and progressively transformed germinal centers of lymph nodes

    Yasuharu Sato, Dai Inoue, Naoko Asano, Katsuyoshi Takata, Hideki Asaoku, Yoshinobu Maeda, Toshiaki Morito, Hirokazu Okumura, Shin Ishizawa, Shoko Matsui, Takayoshi Miyazono, Tamotsu Takeuchi, Naoto Kuroda, Yorihisa Orita, Kiyoshi Takagawa, Masaru Kojima, Tadashi Yoshino

    MODERN PATHOLOGY   25 ( 7 )   956 - 967   2012.7

     More details

    Language:English   Publisher:NATURE PUBLISHING GROUP  

    Progressively transformed germinal centers is a benign condition of unknown pathogenesis characterized by a distinctive variant form of reactive follicular hyperplasia in lymph nodes. We recently reported Ig G4-related disease in progressively transformed germinal centers. However, no large case series has been reported and clinicopathologic findings remain unclear. Here, we report 40 Japanese patients (28 men, 12 women; median age, 56 years) with progressively transformed germinal centers of the lymph nodes who fulfilled the histological diagnostic criteria for IgG4-related disease (IgG4(+) progressively transformed germinal centers), with asymptomatic localized lymphadenopathy involving the submandibular nodes in 24, submandibular and cervical nodes in 14, cervical nodes only in 1, and cervical and supraclavicular nodes in 1. In all, 16 (52%) of 31 examined patients had allergic disease. Histologically, the lymph nodes demonstrated uniform histological findings, namely marked follicular hyperplasia with progressively transformed germinal centers, and localization of the majority of IgG4(+) plasma cells in the germinal centers. Serum IgG4, serum IgE and peripheral blood eosinophils were elevated in 87%, 92% and 53% of examined patients, respectively. Eighteen patients subsequently developed extranodal lesions (including five who developed systemic disease), which on histological examination were consistent with IgG4-related disease. IgG4(+) progressively transformed germinal centers presents with uniform clinicopathological features of asymptomatic localized submandibular lymphadenopathy, which persists and/or relapses, and sometimes progresses to extranodal lesions or systemic disease. Nine patients were administered steroid therapy when the lesions progressed, to which all responded well. We suggest that IgG4+ progressively transformed germinal centers should be included in the IgG4-related disease spectrum. Modern Pathology (2012) 25, 956-967; doi:10.1038/modpathol.2012.54; published online 6 April 2012

    DOI: 10.1038/modpathol.2012.54

    Web of Science

    researchmap

  • Histological and immunohistochemical features of gingival enlargement in a patient with AML

    Norihiro Sonoi, Yoshihiko Soga, Hiroshi Maeda, Koichi Ichimura, Tadashi Yoshino, Kazutoshi Aoyama, Nobuharu Fujii, Yoshinobu Maeda, Mitsune Tanimoto, Richard Logan, Judith Raber-Durlacher, Shogo Takashiba

    ODONTOLOGY   100 ( 2 )   254 - 257   2012.7

     More details

    Language:English   Publisher:SPRINGER  

    Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed both before and after chemotherapy. The patient was a 39-year-old Japanese woman with AML-M4 showing gingival enlargement. Histological and immunohistochemical features of gingiva and bacterial counts in the periodontal pockets were examined before and after chemotherapy. The results were as follows: (1) infiltration of myelomonocytic blasts in enlarged gingiva; (2) resolution of gingival enlargement with complete remission of AML by anticancer chemotherapy; and (3) the numbers of bacteria in the periodontal pockets were not high and were not altered before or after chemotherapy. In patients with AML-M4, remarkable mucosal enlargement is not generally observed in the body except in the gingiva. We hypothesized that antigens derived from periodontal bacteria, even if they are not present in large numbers, could act as chemoattractants for myelomonocytic leukemic cells.

    DOI: 10.1007/s10266-011-0051-0

    Web of Science

    researchmap

  • Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17

    Hisakazu Nishimori, Yoshinobu Maeda, Takanori Teshima, Haruko Sugiyama, Koichiro Kobayashi, Yoshiko Yamasuji, Sachiyo Kadohisa, Hidetaka Uryu, Kengo Takeuchi, Takehiro Tanaka, Tadashi Yoshino, Yoichiro Iwakura, Mitsune Tanimoto

    BLOOD   119 ( 1 )   285 - 295   2012.1

     More details

    Language:English   Publisher:AMER SOC HEMATOLOGY  

    Chronic GVHD (cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up-regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Significantly greater numbers of Th17 cells were infiltrated in the lung and liver from allogeneic recipients than those from syngeneic recipients. We then evaluated the roles of Th1 and Th17 in cGVHD with the use of IFN-gamma-deficient and IL-17-deficient mice as donors. Infusion of IFN-gamma(-/-) or IL-17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-beta expression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD. (Blood. 2012; 119(1): 285-295)

    DOI: 10.1182/blood-2011-01-332478

    Web of Science

    researchmap

  • 合成レチノイドAm80はTh1とTh17を抑制することにより慢性移植片対宿主病を改善する

    西森 久和, 前田 嘉信, 谷本 光音

    血液・腫瘍内科   124 ( 3 )   197 - 201   2012

  • Am80による慢性GVHDの治療効果と作用機序.

    西森久和, 前田嘉信, 谷本光音

    血液・腫瘍内科   65 ( 2 )   223 - 230   2012

     More details

  • Germinal center B-cell-like diffuse large B-cell lymphoma of the duodenum is associated with t(14;18) translocation

    Maiko Tamura, Katsuyoshi Takata, Yasuharu Sato, Naoya Nakamura, Yara Yukie Kikuti, Koichi Ichimura, Takehiro Tanaka, Akira Tari, Yoshinobu Maeda, Mitsune Tanimoto, Hiroyuki Okada, Tadashi Yoshino

    PATHOLOGY INTERNATIONAL   61 ( 12 )   742 - 748   2011.12

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    Diffuse large B-cell lymphoma (DLBCL) rarely involves the duodenum, and its clinicopathological characteristics have not been well elucidated. We performed clinicopathological examinations and identified 15 patients with duodenal DLBCL using 18 gastric or colonic DLBCL as a control. Eleven of the 15 patients (73%) were subclassified by immunohistochemical analysis according to the Choi algorithm as germinal center B-cell-like (GCB) type, whereas the 18 control gastric and colonic DLBCL were predominantly subclassified as activated B-cell-like (ABC) type. The classifications according to organ involvement were statistically significant (P= 0.011 and P= 0.035). Macroscopically, the GCB lesions were varied, while all ABC lesions were ulcerative. Fluorescence in situ hybridization analysis revealed a higher frequency of t(14;18) translocation in patients with duodenal DLBCL (3 of 13) as compared with non-duodenal gastrointestinal tract DLBCL (0 of 18), however, the difference was not significant (P = 0.064). Furthermore, the three patients with t(14;18) translocations were classified as GCB. In addition, overall survival of patients was statistically different between those with and without t(14;18) translocation (P= 0.040). In conclusion, duodenal DLBCL predominantly exhibits GCB-type tumors and the frequency of t(14;18) translocation appears to be higher in duodenal GCB-type DLBCL compared to non-duodenal tumors.

    DOI: 10.1111/j.1440-1827.2011.02748.x

    Web of Science

    researchmap

  • Nodal follicular lymphoma without complete follicular dendritic cell networks is related to localized clinical stage

    Wei Cui, Lisha Che, Yasuharu Sato, Xingang Huang, Katsuyoshi Takata, Yorihisa Orita, Naoe Goto, Yoshinobu Maeda, Mitsune Tanimoto, Tadashi Yoshino

    PATHOLOGY INTERNATIONAL   61 ( 12 )   737 - 741   2011.12

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    Follicular lymphoma is the most common low-grade lymphoma and it frequently presents with a systemic disease, often showing advanced clinical stage (III/IV). The lymphoma cells are usually growing associated with follicular dendritic cell (FDC) networks. Abnormal FDC networks have been reported in duodenal follicular lymphoma, in which cases exhibit lower clinical stages than the nodal cases. In the present study, we analyzed the FDC network distribution pattern of 242 nodal follicular lymphomas by immunohistochemistry. Out of the 242 cases, 27 cases (11%) demonstrated an atypical pattern of FDC networks, in which the CD21 staining totally or partially disappeared in the neoplastic follicles. Furthermore, we compared the clinical data of these 27 cases and 58 typical FDC network cases of follicular lymphoma. We found that in the typical cases, 52 out of 58 patients (90%) showed advanced clinical stage (III or IV), whereas 10 of 27 (37%) atypical FDC network cases showed localized clinical stage (I or II) (P < 0.01). In conclusion, nodal follicular lymphoma with total loss or partially disrupted FDC networks therefore show a lower clinical stage.

    DOI: 10.1111/j.1440-1827.2011.02736.x

    Web of Science

    researchmap

  • Successful Extracorporeal Life Support for Life-threatening Hypercapnia with Bronchiolitis Obliterans after Allogeneic Hematopoietic Stem Cell Transplantation

    Koichi Waseda, Yasushi Tanimoto, Shingo Ichiba, Nobuaki Miyahara, Toshi Murakami, Nobuaki Ochi, Michihisa Terado, Osamu Nagano, Yoshinobu Maeda, Arihiko Kanehiro, Yoshihito Ujike, Mitsune Tanimoto

    ACTA MEDICA OKAYAMA   65 ( 6 )   403 - 406   2011.12

     More details

    Language:English   Publisher:OKAYAMA UNIV MED SCHOOL  

    Bronchiolitis obliterans (BO) is a disease with a poor prognosis, and a key factor that limits long-term survival after allogeneic hematopoietic stem cell transplantation (HSCT). We here report a case of a 31-year woman with acute lymphatic leukemia, which was treated by chemotherapy and HSCT, and consequently developed BO 2 years after HSCT. A non-tuberculous mycobacterial infection occurred and showed gradual exacerbation. She started taking anti-mycobacterial drugs, but lost appetite, felt tired and finally lost consciousness one month after beginning medication. Arterial blood gas revealed marked hypercapnia. Using extracorporeal life support (ECLS), the carbon dioxide concentration was reduced and her consciousness recovered. To our knowledge, this is the first case in which ECLS was successfully used for hypercapnia in a patient with BO.

    Web of Science

    researchmap

  • Cyclin D2 is overexpressed in proliferation centers of chronic lymphocytic leukemia/small lymphocytic lymphoma

    Takuro Igawa, Yasuharu Sato, Katsuyoshi Takata, Soichiro Fushimi, Maiko Tamura, Naoya Nakamura, Yoshinobu Maeda, Yorihisa Orita, Mitsune Tanimoto, Tadashi Yoshino

    CANCER SCIENCE   102 ( 11 )   2103 - 2107   2011.11

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    The D cyclins are important cell cycle regulatory proteins involved in the pathogenesis of some lymphomas. Cyclin D1 overexpression is a hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 have not been shown to be closely associated with any particular subtype of lymphoma. In the present study, we found that cyclin D2 was specifically overexpressed in the proliferation centers (PC) of all cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) examined (19/19). To examine the molecular mechanisms underlying this overexpression, we immunohistochemically examined the expression of nuclear factor (NF)-kappa B, p15, p16, p18, and p27 in the PC of six patients. Five cases showed upregulation of NF-kappa B expression, which is known to directly induce cyclin D2 by binding to the promoter region of CCND2. All six PC examined demonstrated downregulation of p27 expression. In contrast, upregulation of p15 expression was detected in five of six PC examined. This discrepancy suggests that unknown cell cycle regulatory mechanisms involving NF-kappa B-related pathways are also involved, because NF-kappa B upregulates cyclin D2 not only directly, but also indirectly through c-Myc, which is believed to downregulate both p27 and p15. In conclusion, cyclin D2 is overexpressed in the PC of CLL/SLL and this overexpression is due, in part, to the upregulation of NF-kappa B-related pathways. (Cancer Sci 2011; 102: 2103-2107)

    DOI: 10.1111/j.1349-7006.2011.02046.x

    Web of Science

    researchmap

  • The utility of positron emission tomography/computed tomography in the staging of extranodal natural killer/T-cell lymphoma

    Hideaki Fujiwara, Yoshinobu Maeda, Yuichiro Nawa, Masayuki Yamakura, Daisuke Ennishi, Yukihiro Miyazaki, Katsuji Shinagawa, Masamichi Hara, Kosei Matsue, Mitsune Tanimoto

    EUROPEAN JOURNAL OF HAEMATOLOGY   87 ( 2 )   123 - 129   2011.8

     More details

    Language:English   Publisher:WILEY-BLACKWELL  

    Natural killer (NK)/T-cell lymphoma cases are rarely discovered using positron emission tomography/computed tomography (PET/CT). We compared the utility of PET/CT and that of conventional methods (CMs; CT with IV contrast, biopsies from primary sites, and bone marrow examinations) in the staging of extranodal NK/T-cell lymphoma. Nineteen untreated patients with extranodal NK/T-cell lymphoma at three institutions were analyzed. PET/CT and CMs were applied for initial workups following diagnosis. PET/CT and CMs were compared and evaluated for their ability to detect tumor lesions and their influence on the staging and treatment strategies. In total, 116 lesions were detected by CM and PET/CT. Using PET/CT, 108 lesions (93%) were discovered. The number of nodal lesions was 28: all were positive by PET/CT and 26 (93%) by CMs. The number of extranodal lesions was 89: 84 (94%) and 54 (61%) lesions were positive by PET/CT and CMs, respectively. PET/CT was superior to CMs in detecting cutaneous lesions [31/31 lesions (100%) vs. 20/31 lesions (65%), respectively; P = 0.042]. Bone marrow involvement was confirmed pathologically in only seven patients; four cases (57%) were positive by PET/CT. Using CMs, ten patients (53%) were stages I-II and nine (47%) were stages III-IV. Using PET/CT, eight patients (42%) were in stages I-II and 11 (58%) were in stages III-IV. PET/CT findings altered the stage and treatment strategy in two cases (11%). Our study demonstrated that PET/CT is a useful tool for detecting extranodal lesions in NK/T-cell lymphoma, particularly cutaneous lesions. PET/CT may therefore influence future staging and treatment strategies.

    DOI: 10.1111/j.1600-0609.2011.01645.x

    Web of Science

    researchmap

  • Bacterial substitution of coagulase-negative staphylococci for streptococci on the oral mucosa after hematopoietic cell transplantation

    Yoshihiko Soga, Yoshinobu Maeda, Fumihiko Ishimaru, Mitsune Tanimoto, Hiroshi Maeda, Fusanori Nishimura, Shogo Takashiba

    SUPPORTIVE CARE IN CANCER   19 ( 7 )   995 - 1000   2011.7

     More details

    Language:English   Publisher:SPRINGER  

    Coagulase-negative staphylococci (CoNS) are frequently isolated from blood cultures of hematopoietic cell transplantation (HCT) patients. Generally, the use of central venous catheters is recognized as a significant risk factor for CoNS infection, while the impact of CoNS infection from oral ulcerative mucositis, which occurs frequently in HCT, may be underestimated. Here, we examined the bacteria on the buccal mucosa after HCT.
    Sixty-one patients were examined for bacteria on the buccal mucosa routinely once a week from 1 week before to 3 weeks after allogeneic HCT. Subjects were divided into groups with short and long periods of antibiotic use, and differences in bacterial substitution were evaluated. The relationships between type of HCT (conventional HCT or RIST) and bacterial substitution were also evaluated.
    The changes in detection frequencies of CoNS and alpha-streptococci from before to 3 weeks after HCT were significant (P < 0.05, chi (2) test): 14.5-53.3% and 92.7-53.1%, respectively. Significant bacterial substitution of CoNS for streptococci was observed in the long-term antibiotic use group (P < 0.05, chi (2) test), but also occurred in cases with short-term or no antibiotic use. No relationships between type of HCT (conventional HCT or RIST) were observed.
    Bacterial substitution of CoNS for streptococci occurred frequently on the buccal mucosa after HCT. In addition to antibiotic use, environmental factors may be involved in bacterial substitution. It is important to consider the presence of oral mucositis in CoNS infection after HCT.

    DOI: 10.1007/s00520-010-0923-9

    Web of Science

    researchmap

  • Regulatory T cells and IL-17-producing cells in graft-versus-host disease

    Takanori Teshima, Yoshinobu Maeda, Katsutoshi Ozaki

    IMMUNOTHERAPY   3 ( 7 )   833 - 852   2011.7

     More details

    Language:English   Publishing type:Book review, literature introduction, etc.   Publisher:FUTURE MEDICINE LTD  

    Graft-versus-host disease (GvHD), a major complication following allogeneic hematopoietic stem cell transplantation, is mediated by donor-derived T cells. On activation with alloantigens expressed on host antigen-presenting cells, naive CD4(+) T cells differentiate into T-helper cell subsets of effector T cells expressing distinct sets of transcriptional factors and cytokines. Classically, acute GvHD was suggested to be predominantly related to Th1 responses. However, we now face a completely different and complex scenario involving possible roles of newly identified Th17 cells as well as Tregs in GvHD. Accumulating data from experimental and clinical studies suggest that the fine balance between Th1, Th2, Th17 and Tregs after transplantation may be an important determinant of the severity, manifestation and tissue distribution of GvHD. Understanding the dynamic process of reciprocal differentiation of regulatory and T-helper cell subsets as well as their interactions will be important in establishing novel strategies for preventing and treating GvHD.

    DOI: 10.2217/IMT.11.51

    Web of Science

    researchmap

  • Allogeneic hematopoietic stem cell transplantation for advanced extranodal natural killer/T-cell lymphoma, nasal type

    Daisuke Ennishi, Yoshinobu Maeda, Nobuharu Fujii, Eisei Kondo, Katsuji Shinagawa, Kazuma Ikeda, Koichi Ichimura, Tadashi Yoshino, Mitsune Tanimoto

    LEUKEMIA & LYMPHOMA   52 ( 7 )   1255 - 1261   2011.7

     More details

    Language:English   Publisher:INFORMA HEALTHCARE  

    The prognosis for patients with advanced or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL) is extremely poor. Thus, allogeneic stem cell transplantation (allo-HSCT) should be considered for this disease. However, reports of allo-HSCT for ENKL are limited because of the rarity of the disease. Here, we describe the clinical course of 12 cases of advanced and refractory ENKL treated with allo-HSCT, including five cases with cord blood transplant. With a median follow-up of 13 months (range, 1-168 months), seven patients are alive in remission, five have died, and one treatment-related death occurred. All patients with disease progression at transplant died of disease progression, whereas seven of eight patients with a complete or partial response are long-term survivors. Allo-HSCT is a feasible and promising consolidation therapy for advanced and relapsed ENKL. The disease status before allo-HSCT is well associated with general outcome, and thus induction treatment is very important for this disease.

    DOI: 10.3109/10428194.2011.572322

    Web of Science

    researchmap

  • Bacterial substitution of coagulase-negative staphylococci for streptococci on the oral mucosa after hematopoietic cell transplantation

    Yoshihiko Soga, Yoshinobu Maeda, Fumihiko Ishimaru, Mitsune Tanimoto, Hiroshi Maeda, Fusanori Nishimura, Shogo Takashiba

    SUPPORTIVE CARE IN CANCER   19 ( 7 )   995 - 1000   2011.7

     More details

    Language:English   Publisher:SPRINGER  

    Coagulase-negative staphylococci (CoNS) are frequently isolated from blood cultures of hematopoietic cell transplantation (HCT) patients. Generally, the use of central venous catheters is recognized as a significant risk factor for CoNS infection, while the impact of CoNS infection from oral ulcerative mucositis, which occurs frequently in HCT, may be underestimated. Here, we examined the bacteria on the buccal mucosa after HCT.
    Sixty-one patients were examined for bacteria on the buccal mucosa routinely once a week from 1 week before to 3 weeks after allogeneic HCT. Subjects were divided into groups with short and long periods of antibiotic use, and differences in bacterial substitution were evaluated. The relationships between type of HCT (conventional HCT or RIST) and bacterial substitution were also evaluated.
    The changes in detection frequencies of CoNS and alpha-streptococci from before to 3 weeks after HCT were significant (P < 0.05, chi (2) test): 14.5-53.3% and 92.7-53.1%, respectively. Significant bacterial substitution of CoNS for streptococci was observed in the long-term antibiotic use group (P < 0.05, chi (2) test), but also occurred in cases with short-term or no antibiotic use. No relationships between type of HCT (conventional HCT or RIST) were observed.
    Bacterial substitution of CoNS for streptococci occurred frequently on the buccal mucosa after HCT. In addition to antibiotic use, environmental factors may be involved in bacterial substitution. It is important to consider the presence of oral mucositis in CoNS infection after HCT.

    DOI: 10.1007/s00520-010-0923-9

    Web of Science

    researchmap

  • Does more intensive therapy have effects on mantle cell lymphoma? A clinical experience from the Lymphoma Treatment Study Group in Japan

    Katsuhiro Miura, Hirotaka Takasaki, Hideki Tsujimura, Masatoshi Kanno, Yoshinobu Maeda, Naoto Tomita, Kazue Takai, Yasufumi Masaki, Jun Takizawa, Hiraku Mori, Yasushi Terasaki, Takashi Yoshida, Jin Takeuchi, Shigeki Motomura

    INTERNATIONAL JOURNAL OF HEMATOLOGY   93 ( 5 )   684 - 686   2011.5

     More details

    Language:English   Publisher:SPRINGER TOKYO  

    DOI: 10.1007/s12185-011-0845-4

    Web of Science

    researchmap

  • Progress of oral care and reduction of oral mucositis-a pilot study in a hematopoietic stem cell transplantation ward

    Yoshihiko Soga, Yuko Sugiura, Kanayo Takahashi, Hitomi Nishimoto, Yoshinobu Maeda, Mitsune Tanimoto, Shogo Takashiba

    SUPPORTIVE CARE IN CANCER   19 ( 2 )   303 - 307   2011.2

     More details

    Language:English   Publisher:SPRINGER  

    Oral mucositis is a common symptomatic complication associated with hematopoietic stem cell transplantation (HCT). We use simple strategies aimed to reduce oral mucositis by keeping the oral cavity clean and moist. Here, we report on the progress of oral care and the changes in the degree of oral mucositis. The purpose of this pilot study is to evaluate the effects of our strategies on the prevalence and the severity of oral mucositis.
    Fifty-three consecutive patients from 2003 to 2006 administered with conventional allogeneic HCT were enrolled in this study. The degree of oral mucositis was evaluated daily in all patients. Our oral care program was divided into two periods: "examination and trial period (2003 and 2004)" and "intensive oral care period (2005 and 2006)." In the latter, an oral care regimen was carried out systematically by a multidisciplinary team.
    Using our oral care strategies, the prevalence of ulcerative oral mucositis was decreased significantly. The rate was reduced from 76% (10 of 13) of patients with ulcerative oral mucositis in 2003 to only 20% (3 of 15) in 2006.
    Our pilot study suggests that oral mucositis in HCT patients can be alleviated by simple strategies aimed at keeping the oral cavity clean and moist.

    DOI: 10.1007/s00520-010-1002-y

    Web of Science

    researchmap

  • Progress of oral care and reduction of oral mucositis-a pilot study in a hematopoietic stem cell transplantation ward

    Yoshihiko Soga, Yuko Sugiura, Kanayo Takahashi, Hitomi Nishimoto, Yoshinobu Maeda, Mitsune Tanimoto, Shogo Takashiba

    SUPPORTIVE CARE IN CANCER   19 ( 2 )   303 - 307   2011.2

     More details

    Language:English   Publisher:SPRINGER  

    Oral mucositis is a common symptomatic complication associated with hematopoietic stem cell transplantation (HCT). We use simple strategies aimed to reduce oral mucositis by keeping the oral cavity clean and moist. Here, we report on the progress of oral care and the changes in the degree of oral mucositis. The purpose of this pilot study is to evaluate the effects of our strategies on the prevalence and the severity of oral mucositis.
    Fifty-three consecutive patients from 2003 to 2006 administered with conventional allogeneic HCT were enrolled in this study. The degree of oral mucositis was evaluated daily in all patients. Our oral care program was divided into two periods: "examination and trial period (2003 and 2004)" and "intensive oral care period (2005 and 2006)." In the latter, an oral care regimen was carried out systematically by a multidisciplinary team.
    Using our oral care strategies, the prevalence of ulcerative oral mucositis was decreased significantly. The rate was reduced from 76% (10 of 13) of patients with ulcerative oral mucositis in 2003 to only 20% (3 of 15) in 2006.
    Our pilot study suggests that oral mucositis in HCT patients can be alleviated by simple strategies aimed at keeping the oral cavity clean and moist.

    DOI: 10.1007/s00520-010-1002-y

    Web of Science

    researchmap

  • Phase II study of SMILE chemotherapy for newly-diagnosed stage IV, relapsed or refractory extranodal NK/T-cell lymphoma, nasal type: the NK-cell Tumor Study Group (NKTSG) study.

    Yamaguchi M, Kwong YL, Kim WS, Maeda Y, Hashimoto C, Suh C, Izutsu K, Ishida F, Isobe Y, Suzumiya J, Kodama T, Kimura H, Hyo R, Nakamura S, Oshimi K, Suzuki R

    J Clin Oncol.   29   4410 - 4416   2011

     More details

  • Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: a Japanese multicenter analysis

    Daisuke Ennishi, Yoshinobu Maeda, Nozomi Niitsu, Minoru Kojima, Koji Izutsu, Jun Takizawa, Shigeru Kusumoto, Masataka Okamoto, Masahiro Yokoyama, Yasushi Takamatsu, Kazutaka Sunami, Akira Miyata, Kayoko Murayama, Akira Sakai, Morio Matsumoto, Katsuji Shinagawa, Akinobu Takaki, Keitaro Matsuo, Tomohiro Kinoshita, Mitsune Tanimoto

    BLOOD   116 ( 24 )   5119 - 5125   2010.12

     More details

    Language:English   Publisher:AMER SOC HEMATOLOGY  

    The influence of hepatitis C virus (HCV) infection on prognosis and hepatic toxicity in patients with diffuse large B-cell lymphoma in the rituximab era is unclear. Thus, we analyzed 553 patients, 131 of whom were HCV-positive and 422 of whom were HCV-negative, with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP)-like chemotherapy. Survival outcomes and hepatic toxicity were compared according to HCV infection. The median follow-up was 31 and 32 months for patients who were HCV-positive and HCV-negative, respectively. HCV infection was not a significant risk factor for prognosis (3-year progression-free survival, 69% vs 77%, P = .22; overall survival, 75% vs 84%, P = .07). Of 131 patients who were HCV-positive, 36 (27%) had severe hepatic toxicity (grade 3-4), compared with 13 of 422 (3%) patients who were HCV-negative. Multivariate analysis revealed that HCV infection was a significant risk factor for severe hepatic toxicity (hazard ratio: 14.72; 95% confidence interval, 6.37-34.03; P < .001). An exploratory analysis revealed that pretreatment transaminase was predictive of severe hepatic toxicity. HCV-RNA levels significantly increased during immunochemotherapy (P = .006). These results suggest that careful monitoring of hepatic function and viral load is indicated during immunochemotherapy for HCV-positive patients. (Blood. 2010;116(24):5119-5125)

    DOI: 10.1182/blood-2010-06-289231

    Web of Science

    researchmap

  • Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: a Japanese multicenter analysis

    Daisuke Ennishi, Yoshinobu Maeda, Nozomi Niitsu, Minoru Kojima, Koji Izutsu, Jun Takizawa, Shigeru Kusumoto, Masataka Okamoto, Masahiro Yokoyama, Yasushi Takamatsu, Kazutaka Sunami, Akira Miyata, Kayoko Murayama, Akira Sakai, Morio Matsumoto, Katsuji Shinagawa, Akinobu Takaki, Keitaro Matsuo, Tomohiro Kinoshita, Mitsune Tanimoto

    BLOOD   116 ( 24 )   5119 - 5125   2010.12

     More details

    Language:English   Publisher:AMER SOC HEMATOLOGY  

    The influence of hepatitis C virus (HCV) infection on prognosis and hepatic toxicity in patients with diffuse large B-cell lymphoma in the rituximab era is unclear. Thus, we analyzed 553 patients, 131 of whom were HCV-positive and 422 of whom were HCV-negative, with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP)-like chemotherapy. Survival outcomes and hepatic toxicity were compared according to HCV infection. The median follow-up was 31 and 32 months for patients who were HCV-positive and HCV-negative, respectively. HCV infection was not a significant risk factor for prognosis (3-year progression-free survival, 69% vs 77%, P = .22; overall survival, 75% vs 84%, P = .07). Of 131 patients who were HCV-positive, 36 (27%) had severe hepatic toxicity (grade 3-4), compared with 13 of 422 (3%) patients who were HCV-negative. Multivariate analysis revealed that HCV infection was a significant risk factor for severe hepatic toxicity (hazard ratio: 14.72; 95% confidence interval, 6.37-34.03; P < .001). An exploratory analysis revealed that pretreatment transaminase was predictive of severe hepatic toxicity. HCV-RNA levels significantly increased during immunochemotherapy (P = .006). These results suggest that careful monitoring of hepatic function and viral load is indicated during immunochemotherapy for HCV-positive patients. (Blood. 2010;116(24):5119-5125)

    DOI: 10.1182/blood-2010-06-289231

    Web of Science

    researchmap

  • Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse

    Saiko Kurosawa, Takuhiro Yamaguchi, Shuichi Miyawaki, Naoyuki Uchida, Toru Sakura, Heiwa Kanamori, Kensuke Usuki, Takuya Yamashita, Yasushi Okoshi, Hirohiko Shibayama, Hirohisa Nakamae, Momoko Mawatari, Kazuo Hatanaka, Kazutaka Sunami, Manabu Shimoyama, Naohito Fujishima, Yoshinobu Maeda, Ikuo Miura, Yoichi Takaue, Takahiro Fukuda

    HAEMATOLOGICA-THE HEMATOLOGY JOURNAL   95 ( 11 )   1857 - 1864   2010.11

     More details

    Language:English   Publisher:FERRATA STORTI FOUNDATION  

    Background
    Patients with acute myeloid leukemia who are treated with conventional chemotherapy still have a substantial risk of relapse; the prognostic factors and optimal treatments after relapse have not been fully established. We, therefore, retrospectively analyzed data from patients with acute myeloid leukemia who had achieved first complete remission to assess their prognosis after first relapse.
    Design and Methods
    Clinical data were collected from 70 institutions across the country on adult patients who were diagnosed with acute myeloid leukemia and who had achieved a first complete remission after one or two courses of induction chemotherapy.
    Results
    Among the 1,535 patients who were treated with chemotherapy alone, 1,015 relapsed. Half of them subsequently achieved a second complete remission. The overall survival was 30% at 3 years after relapse. Multivariate analysis showed that achievement of second complete remission, salvage allogeneic hematopoietic cell transplantation, and a relapse-free interval of 1 year or longer were independent prognostic factors. The outcome after allogeneic transplantation in second complete remission was comparable to that after transplantation in first complete remission. Patients with acute myeloid leukemia and cytogenetic risk factors other than inv(16) or t(8;21) had a significantly worse outcome when they did not undergo salvage transplantation even when they achieved second complete remission.
    Conclusions
    We found that both the achievement of second complete remission and the application of salvage transplantation were crucial for improving the prognosis of patients with acute myeloid leukemia in first relapse. Our results indicate that the optimal treatment strategy after first relapse may differ according to the cytogenetic risk.

    DOI: 10.3324/haematol.2010.027516

    Web of Science

    researchmap

  • Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse

    Saiko Kurosawa, Takuhiro Yamaguchi, Shuichi Miyawaki, Naoyuki Uchida, Toru Sakura, Heiwa Kanamori, Kensuke Usuki, Takuya Yamashita, Yasushi Okoshi, Hirohiko Shibayama, Hirohisa Nakamae, Momoko Mawatari, Kazuo Hatanaka, Kazutaka Sunami, Manabu Shimoyama, Naohito Fujishima, Yoshinobu Maeda, Ikuo Miura, Yoichi Takaue, Takahiro Fukuda

    HAEMATOLOGICA-THE HEMATOLOGY JOURNAL   95 ( 11 )   1857 - 1864   2010.11

     More details

    Language:English   Publisher:FERRATA STORTI FOUNDATION  

    Background
    Patients with acute myeloid leukemia who are treated with conventional chemotherapy still have a substantial risk of relapse; the prognostic factors and optimal treatments after relapse have not been fully established. We, therefore, retrospectively analyzed data from patients with acute myeloid leukemia who had achieved first complete remission to assess their prognosis after first relapse.
    Design and Methods
    Clinical data were collected from 70 institutions across the country on adult patients who were diagnosed with acute myeloid leukemia and who had achieved a first complete remission after one or two courses of induction chemotherapy.
    Results
    Among the 1,535 patients who were treated with chemotherapy alone, 1,015 relapsed. Half of them subsequently achieved a second complete remission. The overall survival was 30% at 3 years after relapse. Multivariate analysis showed that achievement of second complete remission, salvage allogeneic hematopoietic cell transplantation, and a relapse-free interval of 1 year or longer were independent prognostic factors. The outcome after allogeneic transplantation in second complete remission was comparable to that after transplantation in first complete remission. Patients with acute myeloid leukemia and cytogenetic risk factors other than inv(16) or t(8;21) had a significantly worse outcome when they did not undergo salvage transplantation even when they achieved second complete remission.
    Conclusions
    We found that both the achievement of second complete remission and the application of salvage transplantation were crucial for improving the prognosis of patients with acute myeloid leukemia in first relapse. Our results indicate that the optimal treatment strategy after first relapse may differ according to the cytogenetic risk.

    DOI: 10.3324/haematol.2010.027516

    Web of Science

    researchmap

  • Alloantigen expression on non-hematopoietic cells reduces graft-versus-leukemia effects in mice

    Shoji Asakura, Daigo Hashimoto, Shuichiro Takashima, Haruko Sugiyama, Yoshinobu Maeda, Koichi Akashi, Mitsune Tanimoto, Takanori Teshima

    JOURNAL OF CLINICAL INVESTIGATION   120 ( 7 )   2370 - 2378   2010.7

     More details

    Language:English   Publisher:AMER SOC CLINICAL INVESTIGATION INC  

    Allogeneic hematopoietic stem cell transplantation (HSCT) is used effectively to treat a number of hematological malignancies. Its beneficial effects rely on donor-derived T cell-targeted leukemic cells, the so-called graft-versus-leukemia (GVL) effect. Induction of GVL is usually associated with concomitant development of graft-versus-host disease (GVHD), a major complication of allogeneic HSCT. The T cells that mediate GVL and GVHD are activated by alloantigen presented on host antigen-presenting cells of hematopoietic origin, and it is not well understood how alloantigen expression on non-hematopoietic cells affects GVL activity. Here we show, in mouse models of MHC-matched, minor histocompatibility antigen-mismatched bone marrow transplantation, that alloantigen expression on host epithelium drives donor T cells into apoptosis and dysfunction during GVHD, resulting in a loss of GVL activity. During GVHD, programmed death-1 (PD-1) and PD ligand-1 (PD-L1), molecules implicated in inducing T cell exhaustion, were upregulated on activated T cells and the target tissue, respectively, suggesting that the T cell defects driven by host epithelial alloantigen expression might be mediated by the PD-1/PD-L1 pathway. Consistent with this, blockade of PD-1/PD-L1 interactions partially restored T cell effector functions and improved GVL. These results elucidate a previously unrecognized significance of alloantigen expression on non-hematopoietic cells in GVL and suggest that separation of GVL from GVHD for more effective HSCT may be possible in human patients.

    DOI: 10.1172/JCI39165

    Web of Science

    researchmap

  • Statin-independent prognosis of patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy

    D. Ennishi, H. Asai, Y. Maeda, K. Shinagawa, K. Ikeda, M. Yokoyama, Y. Terui, K. Takeuchi, T. Yoshino, K. Matsuo, K. Hatake, M. Tanimoto

    ANNALS OF ONCOLOGY   21 ( 6 )   1217 - 1221   2010.6

     More details

    Language:English   Publisher:OXFORD UNIV PRESS  

    Background: A recent laboratory study indicated that statins impaired the antitumor effects of rituximab by inducing conformational changes in CD20. Although these findings raised significant concerns about statin use during rituximab treatment, their clinical significance is unclear.
    Patients and methods: We conducted a retrospective study investigating the effects of statins on the prognosis of diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Newly diagnosed DLBCL patients were analyzed (n = 256), including 35 patients taking statins.
    Results: The 3-year progression-free survival rates were 84% and 73% (P = 0.38), while the overall survival rates were 89% and 78% (P = 0.28) for those patients treated with and without statins, respectively. After adjusting for the International Prognostic Index and serum cholesterol level, statin use was not associated with prognosis.
    Conclusions: These results indicate that statins do not influence the clinical prognosis of DLBCL treated with RCHOP. Further studies with larger numbers of patients are warranted to confirm the prognostic significance of statins for patients with DLBCL receiving rituximab-containing chemotherapy.

    DOI: 10.1093/annonc/mdp490

    Web of Science

    researchmap

  • Cold agglutinin-induced acrocyanosis in a patient with subclinical chronic lymphocytic leukemia; a beneficial response to rituximab

    Yoshinori Shirafuji, Yoshinobu Maeda, Keiji Iwatsuki

    EUROPEAN JOURNAL OF DERMATOLOGY   20 ( 3 )   394 - 396   2010.5

     More details

    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:JOHN LIBBEY EUROTEXT LTD  

    DOI: 10.1684/ejd.2010.0908

    Web of Science

    researchmap

  • Oral mucositis in patients receiving reduced-intensity regimens for allogeneic hematopoietic cell transplantation: comparison with conventional regimen

    Kanayo Takahashi, Yoshihiko Soga, Yumeno Murayama, Mika Udagawa, Hitomi Nishimoto, Yuko Sugiura, Yoshinobu Maeda, Mitsune Tanimoto, Shogo Takashiba

    SUPPORTIVE CARE IN CANCER   18 ( 1 )   115 - 119   2010.1

     More details

    Language:English   Publisher:SPRINGER  

    Severe oral mucositis induced by allogeneic hematopoietic cell transplantation (HCT) is associated with intolerable pain and risk of systemic bacteremia infection. Differences between conventional HCT and reduced-intensity regimens for allogeneic HCT (RIST) may influence the occurrence and severity of oral mucositis. Here, we evaluated oral mucositis in patients undergoing RIST and compared the results with those in conventional allogeneic HCT patients to facilitate predictive measures for mucositis.
    A total of 127 consecutive patients undergoing HCT (conventional, 63; RIST, 64) were included in this study. Severity of oral mucositis during HCT period was evaluated daily. Differences in severity of mucositis among HCT types were analyzed. Use of morphine to control pain due to oral mucositis was evaluated in each HCT method.
    The severity of oral mucositis was reduced in patients undergoing RIST. Worsening of oral mucositis was delayed in patients receiving RIST. Use of morphine to control pain due to oral mucositis was significantly decreased in patients undergoing RIST compared with those receiving conventional allogeneic HCT.
    The severity of oral mucositis was reduced and the peak day of oral mucositis was delayed in RIST patients compared with those receiving conventional HCT.

    DOI: 10.1007/s00520-009-0637-z

    Web of Science

    researchmap

  • Oral mucositis in patients receiving reduced-intensity regimens for allogeneic hematopoietic cell transplantation: comparison with conventional regimen

    Kanayo Takahashi, Yoshihiko Soga, Yumeno Murayama, Mika Udagawa, Hitomi Nishimoto, Yuko Sugiura, Yoshinobu Maeda, Mitsune Tanimoto, Shogo Takashiba

    SUPPORTIVE CARE IN CANCER   18 ( 1 )   115 - 119   2010.1

     More details

    Language:English   Publisher:SPRINGER  

    Severe oral mucositis induced by allogeneic hematopoietic cell transplantation (HCT) is associated with intolerable pain and risk of systemic bacteremia infection. Differences between conventional HCT and reduced-intensity regimens for allogeneic HCT (RIST) may influence the occurrence and severity of oral mucositis. Here, we evaluated oral mucositis in patients undergoing RIST and compared the results with those in conventional allogeneic HCT patients to facilitate predictive measures for mucositis.
    A total of 127 consecutive patients undergoing HCT (conventional, 63; RIST, 64) were included in this study. Severity of oral mucositis during HCT period was evaluated daily. Differences in severity of mucositis among HCT types were analyzed. Use of morphine to control pain due to oral mucositis was evaluated in each HCT method.
    The severity of oral mucositis was reduced in patients undergoing RIST. Worsening of oral mucositis was delayed in patients receiving RIST. Use of morphine to control pain due to oral mucositis was significantly decreased in patients undergoing RIST compared with those receiving conventional allogeneic HCT.
    The severity of oral mucositis was reduced and the peak day of oral mucositis was delayed in RIST patients compared with those receiving conventional HCT.

    DOI: 10.1007/s00520-009-0637-z

    Web of Science

    researchmap

  • Incidental Detection of Acute Lymphoblastic Leukemia on [(18)F] Fluorodeoxyglucose Positron Emission Tomography

    Daisuke Ennishi, Yoshinobu Maeda, Masami Niiya, Katsuji Shinagawa, Mitsune Tanimoto

    JOURNAL OF CLINICAL ONCOLOGY   27 ( 36 )   e269 - e270   2009.12

     More details

    Language:English   Publisher:AMER SOC CLINICAL ONCOLOGY  

    DOI: 10.1200/JCO.2009.22.7769

    Web of Science

    researchmap

  • Febrile neutropenia and periodontitis: lessons from a case periodontal treatment in the intervals between chemotherapy cycles for leukemia reduced febrile neutropenia

    Yoshihiko Soga, Yoshiko Yamasuji, Chieko Kudo, Kaori Matsuura-Yoshimoto, Kokoro Yamabe, Yuko Sugiura, Yoshinobu Maeda, Fumihiko Ishimaru, Mitsune Tanimoto, Fusanori Nishimura, Shogo Takashiba

    SUPPORTIVE CARE IN CANCER   17 ( 5 )   581 - 587   2009.5

     More details

    Language:English   Publisher:SPRINGER  

    Oral and systemic infections arising from the oral cavity are significant problems in clinical management of patients undergoing leukemia treatment. However, there is significant disparity in the reported incidences of development of periodontal infections. Evidence is limited to those showing the systemic influence of periodontal infection in neutropenic patients. This study indicated an association between febrile neutropenia (FN) and periodontitis in a case in which periodontal treatment in the intervals between chemotherapy cycles reduced FN in subsequent courses of chemotherapy and hematopoietic transplantation (HCT).
    Periodontal treatment was performed in a 61-year-old man with advanced periodontitis, who received HCT following three cycles of chemotherapy. After recovery from neutropenia induced by initial chemotherapy, periodontal treatment was performed in each chemotherapy interval period. Following extraction of teeth with severe advanced periodontitis, all teeth were subjected to periodontal pocket curettage and root planning, which are common periodontal treatments to reduce periodontal pockets harboring anaerobic periodontal bacteria, before HCT.
    Periodontal treatment successfully reduced periodontal pockets from 4.1 +/- 1.5 mm to 3.0 +/- 0.6 mm, which was almost within the healthy range (< 3.0 mm), before HCT. The frequency of FN decreased significantly with increasing cycles of chemotherapy, and decreases in FN corresponded to progress of periodontal treatment. Blood cultures obtained a total of 12 times throughout leukemia treatment were all negative.
    The observations reported here indicate the importance of periodontal treatment in clinical management of patients undergoing leukemia treatment to prevent FN, although all blood cultures were negative.

    DOI: 10.1007/s00520-008-0532-z

    Web of Science

    researchmap

  • The effect of adding rituximab to CHOP-based therapy on clinical outcomes for Japanese patients with diffuse large B-cell lymphoma: a propensity score matching analysis

    Hisakazu Nishimori, Keitaro Matsuo, Yoshinobu Maeda, Yuichiro Nawa, Kazutaka Sunami, Kazuto Togitani, Hidetaka Takimoto, Yasushi Hiramatsu, Toru Kiguchi, Tomofumi Yano, Hiromichi Yamane, Takayuki Tabayashi, Makoto Takeuchi, Masanori Makita, Nobuo Sezaki, Yoshiko Yamasuji, Haruko Sugiyama, Takahiro Tabuchi, Itaru Kataoka, Nobuharu Fujii, Fumihiko Ishimaru, Katsuji Shinagawa, Kazuma Ikeda, Masamichi Hara, Tadashi Yoshino, Mitsune Tanimoto

    INTERNATIONAL JOURNAL OF HEMATOLOGY   89 ( 3 )   326 - 331   2009.4

     More details

    Language:English   Publisher:SPRINGER TOKYO  

    We conducted a retrospective analysis to evaluate the impact on clinical outcomes of adding rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment for diffuse large B-cell lymphoma (DLBCL) patients in Japan. A propensity score method was used to compensate for the non-randomized study design. From January 2000 to December 2004, 378 patients who were newly diagnosed with DLBCL at 13 institutes were enrolled: 123 in the rituximab plus CHOP-based chemotherapy (R+) group, and 255 in the CHOP-based chemotherapy only (R-) group. The complete response rate was significantly higher in the R+ group than in the R- group (77.7 vs. 69.4%, P < 0.001). The progression-free survival (PFS) at 2 years was 62.4% in the R+ group and 57.0% in the R- group. The 2-year overall survival (OS) was 76.9% for the R+ group and 70.5% for the R- group. A multivariate analysis revealed that the addition of rituximab was a strong independent prognostic factor for PFS (hazard ratio 0.64, 95% CI 0.43-0.96, P = 0.031). A subgroup analysis revealed that R+ particularly benefited younger patients (hazard ratio 0.25, 95% CI 0.08-0.75, P = 0.013). IPI also showed significant impact for PFS (hazard ratio 1.82, 95% CI 1.55-2.14 for one score increase, P < 0.001) as well as OS (hazard ratio 2.10, 95% CI 1.71-2.57, P < 0.001). In summary, the addition of rituximab to CHOP-based chemotherapy results in better outcomes for Japanese DLBCL patients, particularly younger patients.

    DOI: 10.1007/s12185-009-0259-8

    Web of Science

    researchmap

  • Clinical Outcomes of Unrelated Donor Umbilical Cord Blood Transplantation for 30 Adults with Hematological Malignancies.

    Kobayashi K, Maeda Y, Hara Y, Nishie-Kataoka M, Nishimori H, Sugiyama H, Kubonishi S, Niiya M, Shinagawa K, Ikeda K, Tanimoto M

    Anticancer Res   5   1763 - 70   2009

     More details

  • Efficacy and Feasibility of IDEA Therapy for Refractory or Relapsed Non-Hodgkin’s Lymphoma.

    Nishimori H, Fujii N, Maeda Y, Matsuoka K, Takenaka K, Shinagawa K, Ikeda K, Matsuo K, Harada M, Tanimoto M

    Anticancer Res   5   1749 - 1754   2009

     More details

  • Prediction of number of apheresis procedures necessary in healthy donors to attain minimally required peripheral blood CD34+ cells.

    Namba N, Matsuo K, Kubonishi S, Kikuchi T, Maeda Y, Niiya M, Shinagawa K, Koide N, Ikeda K, Tanimoto M

    Transfusion   2009

     More details

  • Use of micafungin versus fluconazole for antifungal prophylaxis in neutropenic patients receiving hematopoietic stem cell transplantation

    Yasushi Hiramatsu, Yoshinobu Maeda, Nobuharu Fujii, Takashi Saito, Yuichiro Nawa, Masamichi Hara, Tomofumi Yano, Shoji Asakura, Kazutaka Sunami, Takayuki Tabayashi, Akira Miyata, Ken-ichi Matsuoka, Katsuji Shinagawa, Kazuma Ikeda, Keitaro Matsuo, Mitsune Tanimoto

    INTERNATIONAL JOURNAL OF HEMATOLOGY   88 ( 5 )   588 - 595   2008.12

     More details

    Language:English   Publisher:SPRINGER TOKYO  

    A prospective randomized clinical trial assessed the efficacy and tolerance of micafungin compared with that of standard fluconazole treatment in patients undergoing hematopoietic stem cell transplantation (HSCT). Adult patients (n = 106) were randomly assigned to receive prophylaxis with either micafungin 150 mg (n = 52), or fluconazole 400 mg (n = 52). Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and the absence of proven or probable IFI through the end of the 4-week period following treatment. The overall efficacy of micafungin was comparable to that of fluconazole (94 vs. 88%; difference 6.0%; 95% confidence interval, -5.4 to +17.4%; P = 0.295). A total of 2 (4.0%) of 50 patients in the micafungin arm and 6 (12.0%) of 50 patients in the fluconazole arm received empirical antifungal therapy (P = 0.06). Micafungin treatment did not result in increasing adverse effects and had a safe profile as fluconazole in neutropenic patients. This randomized trial indicates that the efficacy and tolerance of micafungin 150 mg was comparable to that of fluconazole 400 mg, suggesting that micafungin at 150 mg daily represents a valuable new treatment option for antifungal prophylaxis in HSCT recipients.

    DOI: 10.1007/s12185-008-0196-y

    Web of Science

    researchmap

  • Identification of CD123(+) myeloid dendritic cells as an early-stage immature subset with strong tumoristatic potential

    Jun Shi, Kazuma Ikeda, Yosinobu Maeda, Katsuji Shinagawa, Aiji Ohtsuka, Hajime Yamamura, Mitsune Tanimoto

    CANCER LETTERS   270 ( 1 )   19 - 29   2008.10

     More details

    Language:English   Publisher:ELSEVIER IRELAND LTD  

    CD123 has been identified as a specific surface marker for plasmacytoid dendritic cells (PDCs). However, CD123 has recently been shown to be expressed on freshly isolated or in vitro generated myeloid dendritic cells (MDCs). In this article, we investigated whether the expression of CD123 on monocyte-derived MDCs was related to their function, especially to tumor-inhibiting potential. MDCs were induced from cord blood CD14(+) monocytes with granulocyte-macro phage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 7 days, and then CD123(+) cells were isolated by positive immunomagnetic cell selection. We observed that CD123(+) cells lost monocyte CD14 expression, acquired immature myeloid dendritic cell phenotype and morphology. They exerted more significant endocytosis and less antigen-presenting function than CD123-MDCs which are often referred to as typical MDCs. Meanwhile, CD123(+) MDCs exhibited more significant tumor-inhibiting activity toward hematological tumor cell lines of U937 and Jurkat even at a low effector:target ratio. CD123(+) MDCs expressed higher level of cytoplasmic TNF-alpha-related apoptosis-inducing ligand (TRAIL), but no detectable surface TRAIL and very little soluble TRAIL. Pretreatment with recombinant human TRAIL receptor 2:Fc fusion protein significantly reduced the tumor-inhibiting effect of CD123(+) MDCs, but not of CD123(-) MDCs. Overall, our data demonstrated that CD123(+) MDCs were an early-stage immature DC subset, with a significant tumor-inhibiting activity partially via involvement of enhanced cytoplasmic TRAIL. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.canlet.2008.04.048

    Web of Science

    researchmap

  • Combined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease

    Isao Tawara, Yoshinobu Maeda, Yaping Sun, Kathleen P. Lowler, Chen Liu, Tonionii Toubai, Andrew N. J. McKenzie, Pavan Reddy

    EXPERIMENTAL HEMATOLOGY   36 ( 8 )   988 - 996   2008.8

     More details

    Language:English   Publisher:ELSEVIER SCIENCE INC  

    The rote of T helper (Th) 1 and Th2 polarization in acute graft-vs-host-disease (GVHD) is unclear. We investigated the role of Th2 cytokine secretion by utilizing donor T cells that cannot make interleukin (IL)-4, IL-5, IL-9, and IL-13 from quadruple cytokine-deficient (Quad-KO) animals, in a well-characterized BALB/c - C57BL/6 model of allogeneic bone marrow transplantation. B6 recipients of BALB/c Quad-KO T cells demonstrated greater clinical severity, target organ damage, and mortality from GVHD than recipients of BALB/c wild-type (WT) T cells. When compared with donor T cells that are deficient in signal transducers and activators of transcription 6 signaling or the signature Th2 cytokine, IL-4, Quad-KO T cells demonstrated greater GVHD mortality. Mechanistic studies demonstrated that Quad-KO T cells demonstrated enhanced T-cell proliferation than WT T cells when stimulated with either allogeneic antigen-presenting cells or with nonspecific stimuli, such as anti-CD3 monoclonal antibody. Quad-KO T cells also secreted greater amounts of Th1 cytokines and IL-17 compared to WT T cells. Deficiency of Th2 cytokines, however, did not alter the allospecific cytotoxic responses, the numbers of immunoregulatory CD4(+)CD25(+) Foxp3(+) T cells or their suppressive functions. Our data thus unequivocally demonstrate that deficiency of the four classical Th2 cytokine enhances T-cell proliferative responses and aggravates GVHD. (c) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

    DOI: 10.1016/j.exphem.2008.02.010

    Web of Science

    researchmap

  • Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase-dependent DC functions and regulates experimental graft-versus-host disease in mice

    Pavan Reddy, Yaping Sun, Tomomi Toubai, Raimon Duran-Struuck, Shawn G. Clouthier, Elizabeth Weisiger, Yoshinobu Maeda, Isao Tawara, Oleg Krijanovski, Erin Gatza, Chen Liu, Chelsea Malter, Paolo Mascagni, Charles A. Dinarello, James L. M. Ferrara

    JOURNAL OF CLINICAL INVESTIGATION   118 ( 7 )   2562 - 2573   2008.7

     More details

    Language:English   Publisher:AMER SOC CLINICAL INVESTIGATION INC  

    Histone deacetylase (HDAC) inhibitors are antitumor agents that also have antiinflammatory properties. However the mechanisms of their immunomodulatory functions are not known. We investigated the mechanisms of action of 2 HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and ITF 2357, on mouse DC responses. Pretreatment of DCs with HDAC inhibitors significantly reduced TLR-induced secretion of proinflammatory cytokines, suppressed the expression of CD40 and CD80, and reduced the in vitro and in vivo allo-stimulatory responses induced by the DCs. In addition, injection of DCs treated ex vivo with HDAC inhibitors reduced experimental graft-versus-host disease (GVHD) in a murine allogeneic BM transplantation model. Exposure of DCs to HDAC inhibitors increased expression of indoleamine 2.3-dioxygenase (IDO), a suppressor of DC function. Blockade of IDO in WT DCs with siRNA and with DCs from IDO-deficient animals caused substantial reversal of HDAC inhibition-induced in vitro suppression of DC-stimulated responses. Direct injection of HDAC inhibitors early after allogeneic BM transplantation to chimeric animals whose BM-derived cells lacked IDO failed to protect from GVHD, demonstrating an in vivo functional role for IDO. Together, these data show that HDAC inhibitors regulate multiple DC functions through the induction of IDO and suggest that they may represent a novel class of agents to treat immune-mediated diseases.

    DOI: 10.1172/JCI34712

    Web of Science

    researchmap

  • Lymphopenia-induced proliferation of donor T cells reduces their capacity for causing acute graft-versus-host disease

    Yoshinobu Maeda, Isao Tawara, Takanori Teshima, Chen Liu, Daigo Hashimoto, Ken-ichi Matsuoka, Mitsune Tanimoto, Pavan Reddy

    EXPERIMENTAL HEMATOLOGY   35 ( 2 )   274 - 286   2007.2

     More details

    Language:English   Publisher:ELSEVIER SCIENCE INC  

    Objective. T cells that undergo lymphopenia-induced proliferation (LIP) are characterized by greater effector and anti-tumor function than naive T cells. But the ability of these T cells in causing graft-versus-host disease (GVHD) is not known.
    Methods. We tested the hypothesis that donor T cells that had undergone LIP would cause more severe GVHD than naive T cells by utilizing well-characterized murine experimental models of allogeneic bone marrow transplantation (BMT).
    Results. Contrary to our hypothesis, LIP of donor T cells under either noninflammatory or irradiated conditions caused significantly reduced GVHD as determined by survival, clinical, pathologic, and biochemical parameters than naive T cells. Compared to naive donor T cells, LIP T cells demonstrated reduced expansion in vivo and in vitro after allogeneic BMT. The reduction in GVHD mortality and severity was observed across multiple strains after allogeneic BMT. In vivo mechanistic studies by cell depletion demonstrated an increase in the CD44(hi) "memory" phenotype T cells and not the CD4(+)CD25(+) T cell subset to be critical for the reduction in GVHD.
    Conclusions. These data demonstrate that LIP of T cells regulates acute GVHD severity in contrast to their ability to cause increased allograft rejection, autoimmunity, or anti-tumor immunity. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc.

    DOI: 10.1016/j.exphem.2006.10.010

    Web of Science

    researchmap

  • Lymphopenia-induced proliferation of donor T cells reduces their capacity for causing acute graft-versus-host disease

    Yoshinobu Maeda, Isao Tawara, Takanori Teshima, Chen Liu, Daigo Hashimoto, Ken-ichi Matsuoka, Mitsune Tanimoto, Pavan Reddy

    EXPERIMENTAL HEMATOLOGY   35 ( 2 )   274 - 286   2007.2

     More details

    Language:English   Publisher:ELSEVIER SCIENCE INC  

    Objective. T cells that undergo lymphopenia-induced proliferation (LIP) are characterized by greater effector and anti-tumor function than naive T cells. But the ability of these T cells in causing graft-versus-host disease (GVHD) is not known.
    Methods. We tested the hypothesis that donor T cells that had undergone LIP would cause more severe GVHD than naive T cells by utilizing well-characterized murine experimental models of allogeneic bone marrow transplantation (BMT).
    Results. Contrary to our hypothesis, LIP of donor T cells under either noninflammatory or irradiated conditions caused significantly reduced GVHD as determined by survival, clinical, pathologic, and biochemical parameters than naive T cells. Compared to naive donor T cells, LIP T cells demonstrated reduced expansion in vivo and in vitro after allogeneic BMT. The reduction in GVHD mortality and severity was observed across multiple strains after allogeneic BMT. In vivo mechanistic studies by cell depletion demonstrated an increase in the CD44(hi) "memory" phenotype T cells and not the CD4(+)CD25(+) T cell subset to be critical for the reduction in GVHD.
    Conclusions. These data demonstrate that LIP of T cells regulates acute GVHD severity in contrast to their ability to cause increased allograft rejection, autoimmunity, or anti-tumor immunity. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc.

    DOI: 10.1016/j.exphem.2006.10.010

    Web of Science

    researchmap

  • Predominant infiltration of monocytes in chronic graft-versus-host disease

    Noriko Namba, Katsuii Shinagawa, Nobuharu Fujii, Yoshinobu Maeda, Fumihiko Ishimaru, Kazurna Ikeda, Toshimitsu Matsui, Mitsune Tanimoto, Yoshio Katayama

    TRANSPLANTATION   83 ( 2 )   220 - 224   2007.1

     More details

    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Pathogenesis of chronic graft-versus-host disease (cGVHD) is largely unknown. It is important to determine the responsible cell types and the factors that play roles to recruit these cells into sites of disease. We examined whether monocytes and chemokine fractalkine/receptor CX3CR1 axis might be involved. We found that the absolute number of CX3CR1 + monocytes in the blood was significantly decreased in patients with severe cGVHD. Immunohistochemical staining revealed the extensive infiltration of CD 14 + cells as well as strong expression of fractalkine in the cGVHD skin. The number of infiltrated CD14+ cells on the margin of fractatkine+ epidermis was larger in cGVHD skin compared to that of acute graft-versus-host disease, whereas no difference was observed in CD3 + T cells. These results suggest that CX3CR1+ monocytes may be recruited from the circulation to the fractalkine + epidermis in cGVHD, and highlight these cells and this chemokine/receptor axis as additional targets for cGVHD therapy.

    DOI: 10.1097/01.tp.0000245080.71722.87

    Web of Science

    researchmap

  • Predominant infiltration of monocytes in chronic graft-versus-host disease

    Noriko Namba, Katsuii Shinagawa, Nobuharu Fujii, Yoshinobu Maeda, Fumihiko Ishimaru, Kazurna Ikeda, Toshimitsu Matsui, Mitsune Tanimoto, Yoshio Katayama

    TRANSPLANTATION   83 ( 2 )   220 - 224   2007.1

     More details

    Language:English   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Pathogenesis of chronic graft-versus-host disease (cGVHD) is largely unknown. It is important to determine the responsible cell types and the factors that play roles to recruit these cells into sites of disease. We examined whether monocytes and chemokine fractalkine/receptor CX3CR1 axis might be involved. We found that the absolute number of CX3CR1 + monocytes in the blood was significantly decreased in patients with severe cGVHD. Immunohistochemical staining revealed the extensive infiltration of CD 14 + cells as well as strong expression of fractalkine in the cGVHD skin. The number of infiltrated CD14+ cells on the margin of fractatkine+ epidermis was larger in cGVHD skin compared to that of acute graft-versus-host disease, whereas no difference was observed in CD3 + T cells. These results suggest that CX3CR1+ monocytes may be recruited from the circulation to the fractalkine + epidermis in cGVHD, and highlight these cells and this chemokine/receptor axis as additional targets for cGVHD therapy.

    DOI: 10.1097/01.tp.0000245080.71722.87

    Web of Science

    researchmap

  • MDSを合併した先端巨大症に対するオクトレオチドによる1治療例

    三好智子, 大塚文男, 稲垣兼一, 鈴木二郎, 大谷寛之, 後藤順子, 三村由香里, 小倉俊郎, 影山甚郷, 前田嘉信, 槇野博史

    日本内分泌学会雑誌   83 79-81:,2007   2007

     More details

  • MDSを合併した先端巨大症に対するオクトレチオドによる1治療例

    三好智子, 大塚文男, 稲垣兼一, 鈴木二郎, 大谷寛之, 後藤順子, 三村由香里, 小倉俊郎, 景山甚郷, 前田嘉信, 槇野博史

    日本内分泌学会雑誌   83   79 - 81   2007

     More details

  • Chronic lymphoproliferative disorder with regulatory T-cell phenotype

    Tomoko Kikuchi, Yoshio Katayama, Shiro Kubonishi, Toshiyuki Watanabe, Yukari Watanabe, Ken-ichi Matsuoka, Yoshinobu Maeda, Noriko Namba, Taro Masunari, Ryusuke Nasu, Kazuma Ikeda, Mitsune Tanimoto

    AMERICAN JOURNAL OF HEMATOLOGY   81 ( 9 )   713 - 716   2006.9

     More details

    Language:English   Publisher:WILEY-LISS  

    We report a case of T-cell chronic lymphoproliferative disorder (CLPD) that shows neither features of T-cell prolymphocytic leukemia nor disease progression for more than 34 months. Flow cytometric analyses of the lymphocytes revealed high expression of CD4 and CD25. Up-regulation of Foxp3, a master regulatory gene for developmental differentiation of regulatory T cells (Treg), was confirmed at mRNA and protein levels. To our knowledge, this is the first case of extremely indolent CLPD with Treg phenotype.

    DOI: 10.1002/ajh.20688

    Web of Science

    researchmap

  • Single-dose daily infusion of cyclosporine for prevention of graft-versus-host disease after allogeneic bone marrow transplantation from HLA allele-matched, unrelated donors

    Y Nawa, M Hara, K Tanimoto, K Nakase, T Kozuka, Y Maeda

    INTERNATIONAL JOURNAL OF HEMATOLOGY   83 ( 2 )   159 - 163   2006.2

     More details

    Language:English   Publisher:CARDEN JENNINGS PUBL CO LTD  

    Peak blood concentration of cyclosporine (CsA) in renal transplantation patients was recently reported to be associated with clinical efficacy. We therefore evaluated the toxicity and efficacy of a regimen of once-daily infusion of CsA plus a short course of methotrexate as prophylaxis of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation from an HLA allele-matched, unrelated donor. Nineteen patients with hematologic malignancies received CsA, 3 mg/kg per day, as a 4-hour intravenous (IV) infusion from day -1. After engraftment, patients received CsA orally at twice the IV dose. The CsA dose was adjusted to maintain the blood trough level between 1.50 and 200 ng/mL. Methotrexate was administered IV at doses of 10 mg/m(2) on day 1 and 7 rag/rn2 on days 3,6, and 11. Bone marrow engraftment occurred in all patients. Grade 1 and grade 2 GVHD occurred in 6 (31.6%) and 7 (36.8%) of the 19 patients, respectively. No patient had grade 3 or 4 GVHD. Acute nephrotoxicity developed in 1 (5.3%) of the 19 patients, and hypertension developed in 3 (15.8%) of the 19 patients. We evaluated the pharmacokinetics of 4-hour CsA infusion in 10 patients. Tie mean trough concentration, mean peak concentration, mean time to peak concentration, and area under the curve (24 hours) were 161 +/- 43 ng/mL, 1498 +/- 387 ng/mL, 3.2 +/- 1.0 hours, and 10,848 +/- 1,991 ng(.)h/mL, respectively. This regimen was well tolerated and did not enhance the risk of severe GVHD in patients undergoing allogeneic bone marrow transplantation from an HLA allele-matched, unrelated donor.

    DOI: 10.1532/IJH97.05006

    Web of Science

    researchmap

  • A crucial role for antigen-presenting cells and alloantigen expression in graft-versus-leukemia responses

    P Reddy, Y Maeda, C Liu, OI Krijanovski, R Korngold, JLM Ferrara

    NATURE MEDICINE   11 ( 11 )   1244 - 1249   2005.11

     More details

    Language:English   Publisher:NATURE PUBLISHING GROUP  

    Graft-versus-leukemia ( GVL) response after allogeneic bone marrow transplantation ( BMT) represents one of the most potent forms of immunotherapy against malignant diseases(1). Antigen-presenting cells ( APCs) are crucial for the induction of graft-versus-host disease ( GVHD)(2-6), the most serious complication of allogeneic BMT, but their role in GVL responses is unclear. Using a series of clinically relevant mouse GVL tumor models, we found that APCs and alloantigen expression on tumors are crucial for GVL. Moreover, APCs of host origin predominated in GVL responses although donor APCs contributed as the acuity of tumor burden decreased.

    DOI: 10.1038/nm1309

    Web of Science

    researchmap

  • Critical role of host gamma delta T cells in experimental acute graft-versus-host disease

    Y Maeda, P Reddy, KP Lowler, C Liu, DK Bishop, JLM Ferrara

    BLOOD   106 ( 2 )   749 - 755   2005.7

     More details

    Language:English   Publisher:AMER SOC HEMATOLOGY  

    gamma delta T cells localize to target tissues of graft-versus-host disease (GVHD) and therefore we investigated the role of host gamma delta T cells in the pathogenesis of acute GVHD in several well-characterized allogeneic bone marrow transplantation (BMT) models. Depletion of host gamma delta T cells in wild-type (wt) B6 recipients by administration of anti-T-cell receptor (TCR) gamma delta monoclonal antibody reduced GVHD, and gamma delta T-cell-deficient (gamma delta(-/-)) BM transplant recipients experienced markedly improved survival compared with normal controls (63% vs 10%, P <.001). gamma delta T cells were responsible for this difference because reconstitution of gamma delta(-/-) recipients with gamma delta T cells restored GVHD mortality. gamma delta(-/-) recipients showed decreased serum levels of tumor necrosis factor alpha (TNF-alpha), less GVHD histopathologic damage, and reduced donor T-cell expansion. Mechanistic analysis of this phenomenon demonstrated that dendritic cells (DCs) from gamma delta(-/-) recipients exhibited less allostimulatory capacity compared to wt DCs after irradiation. Normal DCs derived from BM caused greater allogeneic T-cell proliferation when cocultured with gamma delta T cells than DCs cocultured with medium alone. This enhancement did not depend on interferon,gamma (IFN-gamma), TNF-alpha, or CD40 ligand but did depend on cell-to-cell contact. These data demonstrated that the host gamma delta T cells exacerbate GVHD by enhancing the allostimulatory capacity of host antigen-presenting cells.

    DOI: 10.1182/blood-2004-10-4087

    Web of Science

    researchmap

  • Both perforin and Fas ligand are required for the regulation of alloreactive CD8(+) T cells during acute graft-versus-host disease

    Y Maeda, RB Levy, P Reddy, C Liu, SG Clouthier, F Teshima, JLM Ferrara

    BLOOD   105 ( 5 )   2023 - 2027   2005.3

     More details

    Language:English   Publisher:AMER SOC HEMATOLOGY  

    Fas ligand (FasL) and perforin pathways not only are the major mechanisms of T cell-mediated cytotoxicity but also are involved in homeostatic regulation of these T cells. In the present study, we tested whether CD8(+) donor T cells that are deficient in both perforin and FasL (cytotoxic double deficient [cdd]) could induce graft-versus-host disease (GVHD) in a major histocompatibility complex class I-mismatched lethally irradiated murine model. Interestingly, recipients of cdd CD8(+) T cells demonstrated significantly greater serum levels of interferon gamma and tumor necrosis factor alpha and histopathologic damage from GVHD than wild-type (wt) T cells on day 30 after allogeneic bone marrow transplantation (P < .05). Wt and either perforin-deficient or FasL-deficient CD8(+) T cells expanded early after transplantation followed by a contraction phase in which the majority of expanded CD8(+) T cells were eliminated. In contrast, cdd CD8(+) T cells exhibited prolonged expansion and reduced apoptosis to alloantigen stimulation in vivo and in vitro. Together these results suggest that donor cdd CD8(+) T cells expand continuously and cause lethal GVHD, and that both perforin and Fast-are required for the contraction of alloreactive CD8(+) T cells. (C) 2005 by The American Society of Hematology.

    DOI: 10.1182/blood-2004-08-3036

    Web of Science

    researchmap

  • Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect

    P Reddy, Y Maeda, K Hotary, C Liu, LL Reznikov, CA Dinarello, JLM Ferrara

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   101 ( 11 )   3921 - 3926   2004.3

     More details

    Language:English   Publisher:NATL ACAD SCIENCES  

    Acute graft-versus-host disease (GVHD) and leukemic relapse are the two major obstacles to successful outcomes after allogeneic bone marrow transplantation (BMT), an effective therapy for hematological malignancies. Several studies have demonstrated that the dysregulation of proinflammatory cytokines and the loss of gastrointestinal tract integrity contribute to GVHD, whereas the donor cytotoxic responses are critical for graft-versus-leukemia (GVL) preservation. Suberoylanilide hydroxamic acid (SAHA) is currently in clinical trials as an antitumor agent, it inhibits the activity of histone deacetylases and at low doses exhibits anti inflammatory effects by reducing the production of proinflammatory cytokines. Using two well characterized mouse models of BMT, we have studied the effects of SAHA on GVHD severity and GVL activity. Administration of SAHA from day +3 to day +7 after BMT reduced serum levels of the proinflammatory cytokines and decreased intestinal histopathology, clinical severity, and mortality from acute GVHD compared with vehicle-treated animals. However, SAHA had no effect on donor T cell proliferative and cytotoxic responses to host antigens in vivo or in vitro. When mice received lethal doses of tumor cells at the time of BMT, administration of SAHA did not impair GVL activity and resulted in significantly improved leukemia-free survival by using two different tumor and donor/recipient combinations. These findings reveal a critical role for histone deacetylase inhibition in the proinflammatory events contributing to GVHD and suggest that this class of pharmacologic agents may provide a strategy to reduce GVHD while preserving cytotoxic T cell responses to host antigens and maintaining beneficial GVL effects.

    DOI: 10.1073/pnas.0400380101

    Web of Science

    researchmap

  • Paradoxical effects of interleukin-18 on the severity of acute graft-versus-host disease mediated by CD4+ and CD8+ T cell subsets after experimental allogeneic bone marrow transplantation.

    Min CK, Maeda Y, Lowler K, Liu C, Clouthier S, Lofthus D, Weisiger E, Ferrara JL, Reddy P

    Blood   2004

  • Host Dendritic cells alone are sufficient to initiate acute graft-versus-host disease

    Duffner UA, Maeda Y, Cooke KR, Reddy P, Ordemann R, Liu C, Ferrara JL, Teshima T

    J Immunol   2004

     More details

  • Peripheral blood circulating immature cell counts predict CD34+ cell yields in G-CSF-induced PBPC mobilization in healthy donors

    Kozuka T, Ikeda K, Teshima T, Yoshida C, Shinagawa K, Kojima K, Matsuo K, Bessho A, Sunami K, Hiramatsu Y, Maeda Y, Noguchi T, Yamamoto K, Fujii N, Imai T

    Transfusion   2004

  • Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays

    T Ichiba, T Teshima, R Kuick, DE Misek, C Liu, Y Takada, Y Maeda, P Reddy, DL Williams, SM Hanash, JLM Ferrara

    BLOOD   102 ( 2 )   763 - 771   2003.7

     More details

    Language:English   Publisher:AMER SOC HEMATOLOGY  

    The liver, skin, and gastrointestinal tract are major target organs of acute graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT). In order to gain a better understanding of acute GVHD in the liver, we compared the gene expression profiles of livers after experimental allogeneic and syngeneic BMT using oilgonucleotide microarray. At 35 days after allogeneic BMT when hepatic GVHD was histologically evident, genes related to cellular effectors and acute-phase proteins were up-regulated, whereas genes largely related to metabolism and endocrine function were down-regulated. At day 7 after BMT before the development of histologic changes in the liver, interferon gamma (IFN-gamma)-inducible genes, major histocompatibility (MHC) class II molecules, and genes related to leukocyte trafficking had been up-regulated. Immunohistochemistry demonstrated that expression of IFN-gamma protein itself was increased in the spleen but not in hepatic tissue. These results suggest that the increased expression of genes associated with the attraction and activation of donor T cells induced by IFN-gamma early after BMT is important in the initiation of hepatic GVHD in this model and provide new potential molecular targets for early detection and intervention of acute GVHD. (C) 2003 by The American Society of Hematology.

    DOI: 10.1182/blood-2002-09-2748

    Web of Science

    researchmap

  • Interleukin 18 preserves a perforin-dependent graft-versus-leukemia effect after allogeneic bone marrow transplantation

    P Reddy, T Teshima, G Hildebrandt, U Duffner, Y Maeda, KR Cooke, JLM Ferrara

    BLOOD   100 ( 9 )   3429 - 3431   2002.11

     More details

    Language:English   Publisher:AMER SOC HEMATOLOGY  

    We have recently shown that early administration of interleukin 18 (IL-18) after bone marrow transplantation (BMT) attenuates acute graft-versus-host disease (GVHD) in a lethally irradiated parent into F1 (B6-->B6D2F1) BMT model. In this study, we investigated whether IL-18 can maintain graft-versus-leukemia (GVL) effect in this context. B6D2F1 mice received transplants of T-cell-depleted (TCD) bone marrow (BM) and splenic T cells from either syngeneic (H2(b/d)) or allogeneic B6 (H2(b)) donors. Recipient mice were treated with recombinant murine IL-18 or the control diluent. Initial studies demonstrated that IL-18 treatment did not affect the proliferative responses or the cytolytic effector functions of T cells after BMT. In subsequent experiments, animals also received host-type P815 mastocytoma cells at the time of BMT. All syngeneic BM transplant recipients died from leukemia by day 18. The allogeneic BM transplant recipients effectively rejected their leukemia regardless of treatment and IL-18 significantly reduced GVHD-related mortality. Examination of the cytotoxic mechanisms with perforin-deficient donor T cells demonstrated that perforin is critical for the GVL effect. Taken together these data demonstrate that IL-18 can attenuate acute GVHD without impairing the in vitro cytolytic function or the in vivo GVL activity after allogeneic BMT.

    DOI: 10.1182/blood-2002-04-1252

    Web of Science

    researchmap

  • Ureteric obstruction by retroperitoneal lymphoplasmacytic lymphoma.

    Maeda Y, Nawa Y, Tanimoto K, Oshima K, Hara M

    Am J Hematol   2002

     More details

  • Differentiation of monoblastic cell line UG3 into leukemic dendritic cells.

    Fujii N, Ikeda T, Ikeda K, Hiraki A, Kawakami K, Masuda K, Maeda Y, Hatake K, Motoyoshi K, Harada M, Tanimoto M

    Int J Oncol   2002

     More details

  • Extragonadal germ cell tumor with high serum levels of DU-PAN-2.

    Maeda Y, Fujiwara N, Yoshino T, Kiura K, Ueoka H, Harada M

    J Urol   2002

     More details

  • Predictive value of circulating immature cell counts in peripheral blood for timing of peripheral blood progenitor cell collection after G-CSF plus chemotherapy-induced mobilization.

    Kozuka T, Ikeda K, Teshima T, Kojima K, Matsuo K, Bessho A, Sunami K, Hiramatsu Y, Maeda Y, Noguchi T

    Transfusion   2002

     More details

  • uccessful treatment of progressive NK cell lymphoma with allogeneic peripheral stem cell transplantation followed by early cyclosporine tapering and donor leukocyte infusions.

    Makita M, Maeda Y, Takenaka K, Shinagawa K, Sunami K, Hiramatsu Y, Fujii N, Ishimaru F, Ikeda K, Niiya K, Yoshino T, Harada M

    Int J Hematol   2002

     More details

▼display all

Presentations

  • 白血病治療の進歩

    高知Ph陽性白血病治療懇話会  2018 

     More details

  • T細胞性リンパ腫 Up to Date

    悪性リンパ腫セミナー in Tokyo  2018 

     More details

  • 血液悪性疾患に対する治療:どこまで進んだか

    第17回倉敷血液カンファレンス  2018 

     More details

  • GVHD克服に向けて病態から考えよう

    SCT Expert Meeting  2018 

     More details

  • 血液悪性疾患に対する治療の最先端

    府中医師会講演会  2018 

     More details

  • 悪性リンパ腫治療における最近の進歩と岡山大学の取り組み

    第二内科同門会広島県東部地区  2018 

     More details

  • 同種末梢血幹細胞移植後3年で抗リン脂質抗体症候群を発症した1例

    第57回日本血液学会中国四国地方会  2018 

     More details

  • T細胞リンパ腫の最新の治療戦略

    ML Forum in Sapporo  2018 

     More details

  • 悪性リンパ腫治療における最近の進歩と当院の取り組み

    倉敷学術講演会  2018 

     More details

  • GVHD克服に向けて病態から考える

    第17回血液腫瘍フォーラム  2018 

     More details

  • GVHD克服に向けて病態から考える

    京治 血液DIC治療セミナー  2018 

     More details

  • Marginal zone B cell lymphoma治療後に,複視を契機にNeurolymphomatosisとし て再発したと考えられる一例

    第57回日本血液学会中国四国地方会  2018 

     More details

  • 乳房腫脹を契機に診断されPeripheral T-cell lymphoma(PTCL), with T follicular helper phenotypeの1例

    第57回日本血液学会中国・四国地方会  2018 

     More details

  • Effect of Protein Sufficiency Rate on Hospital Length of Stay in Allogeneic HSCT Recipients

    2018 BMT tandem meetings  2018 

     More details

  • 血液悪性疾患治療における最近の進歩

    備後血液疾患研究会  2018 

     More details

  • 血液がん領域のABC

    第17回 中国・四国 臨床腫瘍研究会セミナー  2018 

     More details

  • 同種移植後再発に対する2nd HSCTの後方視的解析;Haploidentical移植の有用性の検討

    第40回日本造血細胞移植学会総会  2018 

     More details

  • 同種造血幹細胞移植におけるたんぱく質充足率が入院日数に与える影響について

    第40回日本造血細胞移植学会総会  2018 

     More details

  • GVHDの基礎

    日本造血幹細胞移植学会 教育講演  2018 

     More details

  • Early Administration of Low-dose IL-2 Intensify GVL with controlling GVHD by Enhancing CD62L on Treg

    第40回 造血細胞移植学会  2018 

     More details

  • Myelin basic proteinが活動性の指標となりえた同種移植後のネララビン関連脊髄炎

    第40回日本造血細胞移植学会総会  2018 

     More details

  • GVHDの基礎と臨床

    造血幹細胞移植拠点セミナー in Tokyo  2018 

     More details

  • 同種造血幹細胞移植患者におけるStenotrophomonas maltophilia菌血症の死亡リスク因子の検討

    第40回日本造血細胞移植学会総会  2018 

     More details

  • 同種造血幹細胞移植患者におけるStenotrophomonas maltophilia菌血症の死亡リスク因子の検討

    第40回日本造血幹細胞移植学会総会  2018 

     More details

  • 慢性移植片対宿主病に対するAM80治療

    シンポジウム:ゲノム医療の最先端  2018 

     More details

  • HLA半合致末梢血幹細胞移植後に発症した進行性多巣性白質脳症の1例

    第56回血液学会中国地方会  2017 

     More details

  • Prognostic impact of renal dysfunction before allogeneic hematopoietic stem cell transplantation

    第39回造血細胞移植学会  2017 

     More details

  • PTCL with EBV infection, IVL-likeが疑われたが、のちに子宮原発ENKLと診断された一例

    第23回中四リンパ腫カンファレンス  2017 

     More details

  • Distinct Phenotypic Characteristics of Relapsed ATL after HSCT Implication of Homogeneity with Treg〜ATL移植後再発における表現型の特徴〜

    第79回日本血液学会学術集会  2017 

     More details

  • GVHDの診断・予防・治療

    第10回造血細胞移植レジデント勉強会  2017 

     More details

  • PTCLにおける新しい治療選択肢

    ML Forum in NAGASAKI  2017 

     More details

  • An analysis about citrate intoxication and electrolytes during PBSCH of healthy donor.

    第79回日本血液学会学術集会  2017 

     More details

  • フォロデシンのPI/II 臨床試験

    PTCL Conference in Okayama  2017 

     More details

  • PTCLの最新の治療戦略

    第15回日本臨床腫瘍学会学術大会 モーニングセミナー  2017 

     More details

  • Successful treatment of acute promyelocytic leukemia complicated with endometrial cancer using arsenic trioxide

    第15回日本臨床腫瘍学会学術集会  2017 

     More details

  • 慢性GVHDの基礎と臨床

    第6回 血液Interactive Forum  2017 

     More details

  • 骨髄異形成症候群に対する同種造血幹細胞移植

    札幌SCTカンファレンス  2017 

     More details

  • Successful treatment of acute promyelocytic leukemia complicated with endometrial cancer using arsenic trioxide

    第15回日本臨床腫瘍学会学術集会  2017 

     More details

  • PTCLの最新の治療戦略

    ML Forum in Chiba  2017 

     More details

  • 造血の話

    「健やかに生きるための疾病論」教養教育科目  2017 

     More details

  • MTX中止により寛解が得られているEBV関連T/NKリンパ増殖性疾患と考えられる1例

    第116回日本内科学会中国地方会  2017 

     More details

  • TMAとGVHDに対する新たな試み

    第7回あきた免疫移植感染症研究会  2017 

     More details

  • 悪性リンパ腫 ~治療の問題点と最近の動向~

    愛媛臨床血液懇話会  2017 

     More details

  • PTCLの最新の治療戦略

    悪性リンパ腫ミーティング  2017 

     More details

  • Granulocyte Transfusions for Neutropenic Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

    The 8 th JSH International Symposium 2017  2017 

     More details

  • 血液疾患における真菌感染マネジメント

    Anifungal Expert Class  2017 

     More details

  • 移植前Ccr値と同種移植成績への影響

    第31回岡山造血幹細胞移植研究会  2017 

     More details

  • Granulocyte Transfusions for Neutropenic Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

    The 8 th JSH International Symposium 2017  2017 

     More details

  • 白血病は治るようになったのか 現状と今後

    尾道市立市民病院がん診療部統括部 学術講演会  2017 

     More details

  • GVHD克服に向けて病態から考える

    鹿児島血液レジデント研究会  2017 

     More details

  • Low-Dose IL-2 Can Intensify Graft-versus-Leukemia Effect without Worsening GVHD Through Sequential Enhancement of Effector T Cell and CD62L+ Regulatory T Cell Subset

    The 59th Annual meeting of American Society of Hematology (ASH)  2017 

     More details

  • Dasatinib投与中にCMV出血性腸炎を発症したPh陽性ALL症例における、幹細胞移植後CMV-DNAモニタリングの有用性

    日本内科学会中国支部第117回中国地方会  2017 

     More details

  • Impact of immune checkpoint inhibitors on subsequent chemotherapy

    ESMO Asia 2017  2017 

     More details

  • Liposomal Alpha-Galactosylceramide Ameliorates Graft-Versus-Host Disease with Remaining Intensified GVL Gained By Dose-Reduction of Posttransplant Cyclophosphamaide after Haploidentical HSCT

    ASH 59th Annual Meeting & Exposition  2017 

     More details

  • Loss of the GVL effect by Distinct Expression of Migration Markers as a Mechanism of Immune Escape in Adult T Cell Leukemia/Lymphoma (ATLL), a Malignant Counterpart of Regulatory T Cells.

    59th ASH Annual Meetihg and Exposition  2017 

     More details

  • PTCLにおける新しい治療選択肢

    The New Era of PTCL Treatment  2017 

     More details

  • 移植後合併症の克服に向けて

    大阪 Hematology Forum  2017 

     More details

  • 悪性リンパ腫治療における 最近の進歩と当院の取り組み

    北日本血液研究会学術講演会  2017 

     More details

  • 乳房原発PTCL,follicular helper typeの一例

    第24回中四リンパ腫カンファレンス  2017 

     More details

  • MZBL治療後にneurolymphomatosisとして再発したと考えられるCD5(+) bcl-2(+) c-myc(+) DLBCLの一例

    第24回中四リンパ腫カンファレンス  2017 

     More details

  • PTCLにおける新しい治療選択肢

    城東 Lymphoma Forum  2017 

     More details

  • 白血病は治るようになったのか 課題と進歩

    若手医師・研修医・学生の為の血液専門医養成講座  2017 

     More details

  • がんに対する免疫療法

    第55回日本癌治療学会 メディカルスタッフのためのセミナー  2017 

     More details

  • メポリズマブが著効したアレルギー性 気管支肺アスペルギルス症の一例

    第58回日本呼吸器学会中国四国地方会  2017 

     More details

  • Comprehensive Analyses of Early Lymphocyte Reconstitution after Haploidentical HSCT with Posttransplant Cyclophosphamide: Coordinated Treg-Dominant T-Cell Reconstitution and Stem Cell-Derived Mature B-Cell with Broad BCR-Repertoir Diversity

    58th ASH Annual Meeting.  2016 

     More details

  • Very Early Dynamics of Regulatory T-Cell Chimerism Significantly Varies According to the Donor Sources

    58th ASH Annual Meeting.  2016 

     More details

  • Impact of Incomplete Blood Count Recovery Prior to Allogeneic Hematopoietic Stem Cell Transplantation on Engraftment and Early Infection in Patients with Acute Myeloid Leukemia

    58th ASH Annual Meeting.  2016 

     More details

  • Successful Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Mild Renal Dysfunction Calculated By Creatinin Clearance

    58th ASH Annual Meeting.  2016 

     More details

  • 臍帯血移植にて寛解を維持しているTriple-hit Lymphomaの1例

    第115回日本内科学会中国地方会(2016.11.26)/岡山県岡山市  2016 

     More details

  • A Calcineurin Inhibitor Does Not Affect the Post-Transplantation Cyclophosphamide -Induced Regulatory T Cell Expansion after Bone Marrow Transplantation in a Murine Chronic Gvhd

    58th ASH Annual Meeting.  2016 

     More details

  • 胸腹水貯留と肝障害を伴い発症したaggressive large granular lymphocytic leukemiaの1例

    第115回日本内科学会中国地方会  2016 

     More details

  • 当院における65歳以上の高齢者同種造血幹細胞移植31例の検討

    第38回 日本造血細胞移植学会  2016 

     More details

  • 同種骨髄移植後にBKウイルス性出血性膀胱炎に罹患し、両側腎瘻・膀胱瘻造設術を要した骨髄異形成症候群の一症例

    第55回日本血液学会中国四国地方会  2016 

     More details

  • リンパ節・肺・心嚢への進展を伴った皮膚原発ALK陰性ALCLの一例

    第55回日本血液学会中国四国地方会  2016 

     More details

  • P-F2-6 von Recklinghausen病に合併したフィラデルフィア染色体陽性T-ALLに対し非血縁者間骨髄移植を施行した1例; Unrelated bone marrow transplantation for Philadelphia chromosome positive T-ALL patient harboring von RecklingHausen disease.

    第36回日本造血細胞移植学会総会. 2014;3(7):9.  2014 

     More details

  • 50 Hla半合致移植後の免疫回復遅延に対する低用量dli施行後に慢性炎症性脱髄性多発神経炎を発症した1例.

    第108回日本内科学会中国地方会例会. 2013;6:1.  2014 

     More details

  • P9-6 Mtx中止直後に一過性の白血球増多を認め,その後自然退縮したmtx-Lpdの一例.

    第53回日本リンパ網内系学会総会,第23回日本樹状細胞研究会,第16回日本血液病理研究会. 2013;5(16):18.  2014 

     More details

  • 31 Primary cutaneous γδ T-cell lymphomaに対し,臍帯血移植を施行した一例.

    第53回日本血液学会中国四国地方会. 2014;3:1.  2014 

     More details

  • 148 ハプロミニ移植後にExophiala dermatitidisにより口唇腫脹を来した1例.

    第109回日本内科学会中国地方会例会. 2013;11:23.  2014 

     More details

  • 134 Mediastinal gray zone lymphomaに対しRituximab併用DA-EPOCH療法を施行した3症例.

    第110回日本内科学会総会 講演会. 2013;4(12):14.  2014 

     More details

  • Primary cutaneous γδT-cell lymphomaに対し、臍帯血移植を施行した一例

    第53回日本血液学会中国四国地方会,2014.3.1(徳島)  2014 

     More details

  • 当科における悪性リンパ腫に対する同種造血幹細胞移植79例について

    第36回日本造血細胞移植学会総会. 2014;3.7-9(沖縄)  2014 

     More details

  • PD-1 pathway of donors and recipients modulate chronic graft-versus-host disease through Th1 and Th17 in mouse model

    第75回日本血液学会学術集会2013.10.11 (札幌)  2014 

     More details

  • Lowering expression levels of inhibitory molecules exacerbate chronic graft-versus-host disease in mouse model

    The 4th JSH International Symposium .2013.05.24 (松山)  2014 

     More details

  • Contribution of the PD-1-PD-L Pathway to Chronic Graft-Versus-Host Disease.

    BMT tandem meeting 2013. 2013.2.13-17 (Salt Lake City).  2014 

     More details

  • マウス慢性GVHDモデルにおけるPD-1経路の重要性

    第36回日本造血幹細胞移植学会総会.20140308(沖縄)  2014 

     More details

  • Host tissue PD-1 pathway contribute to murine chronic graft-versus-host disease via Th1+Th17+ cells

    55th ASH Annual Meeting.2013.12.8 (New Orleans)  2014 

     More details

  • O6-6 同種造血幹細胞移植後のサイトカイン ケモカイン 可溶性分子の変動に対するリコンビナントトロンボモジュリンの影響について(サイト研究会中間報告); Effects of recombinant thrombomodulin for cytokines/chemokines/soluble molecules after allogeneic hematopoietic stem cell transplantation.

    第35回日本造血細胞移植学会総会. 2013;3(7):9.  2014 

     More details

  • P-30 中枢神経原発リンパ腫に対する超大量化学療法の治療成績アップデート; High dose chemotherapy with autologous stem cell rescue for primary central nervous system lymphoma-update 2013.

    第31回日本脳腫瘍学会学術集会. 2013;12(8):10.  2014 

     More details

  • (3)-3-2 20年の経過でWaldenstrom macroglobulinemiaに進展し,びまん性大細胞型B細胞リンパ腫を合併したSchnitzler症候群の一例.

    第52回日本血液学会中国四国地方会. 2013;3:23.  2014 

     More details

  • Warfarin内服中に合併した後天性凝固第5因子インヒビターの症例.

    第108回日本内科学会中国地方会例会. 2013;6:1.  2014 

     More details

  • P2-236 ハプロフル移植を施行した全身性Bacillus cereus多発膿瘍を合併した急性骨髄単球性白血病の一例; Successful haploidentical transplantation in a patient with acute myelomonocytic leukemia with systemic multiple Bacillus cereus abscesses.

    第35回日本造血細胞移植学会総会. 2013;3(7):9.  2014 

     More details

  • P1-155 治療抵抗性血液悪性疾患に対するハプロ移植の検討:単一施設の最新成績; Update results of haploidentical SCT in patients with refractory hematological malignancies at a single institute.

    第35回日本造血細胞移植学会総会. 2013;3(7):9.  2014 

     More details

  • Cd5陽性限局期び漫性大細胞型リンパ腫の特徴と治療成績.

    第110回日本内科学会総会 講演会. 2013;4(12):14.  2014 

     More details

  • 47 著明な血小板増多で発症したcmlの1症例.

    第108回日本内科学会中国地方会例会. 2013;6:1.  2014 

     More details

  • 4-3 TAFRO症候群(Castleman-Kojima病)の1例.

    第52回日本血液学会中国四国地方会. 2013;3:23.  2014 

     More details

  • P1-024 非血縁者間骨髄移植後再発に対してドナーリンパ球輸注療法が著効したGATA2変異を有するMonoMac症候群の1例; Successful donor lymphocyte infusion for a case of MonoMac syndrome relapsed after unrelated bone marrow transplantation.

    第35回日本造血細胞移植学会総会. 2013;3(7):9.  2014 

     More details

  • O2-4 同種造血幹細胞移植後の移植関連凝固障害治療としてのリコンビナント トロンボモジュリン; Recombinant Thrombomodurin For The Treatment Of Transplantation-Associated Coagulopathy After Allogeneic Stem Cell Transplantation.

    第36回日本造血細胞移植学会総会. 2014;3(7):9.  2014 

     More details

  • 2c-Sy15-02 中枢神経原発リンパ腫に対する非照射治癒を目指した超大量化学療法.

    日本脳神経外科学会第72回学術総会. 2013;10(16):18.  2014 

     More details

  • 成人Still病との鑑別を要し,20年の経過でWaldenstrom macroglobulinemia(WM)に進展したSchnitzler症候群の1例

    第107回日本内科学会中国地方会例会  2012 

     More details

  • 急速に増大し、強い癌性疼痛のために Oncological emergencyとして緊急治療行ったFollicular Lymphoma の1例.

    第15回中四リンパ腫カンファレンス  2012 

     More details

  • 中枢神経原発悪性リンパ腫に対する自己末梢血幹細胞移植併用大量化学療法; High dose chemotherapy with autologous stem cell support for Primary CNS Lymphoma

    第34回日本造血細胞移植学会総会  2012 

     More details

  • Mediastinal gray zone lymphomaに対しRituximab併用DA-EPOCH療法を施行した3症例

    第50回日本癌治療学会学術集会  2012 

     More details

  • Bacillus cereus感染症および全身性多発膿瘍を認めた急性骨髄性白血病の1例.

    第13回岡山Supportive Therapy研究会  2012 

     More details

  • von Recklinghausen病患者に合併したminor bcr/abl陽性T-ALL/LBLの一例.

    第15回中四リンパ腫カンファレンス  2012 

     More details

  • 高悪性度形質細胞性腫瘍に対してHyper CVAD/bortezomib療法を施行した2例

    第106回日本内科学会中国地方会例会  2012 

     More details

  • HLA ClassII抗体を有するPhALL患者に対するハプロ移植の一例.

    第26回岡山造血幹細胞移植研究会  2012 

     More details

  • わかりやすいGVHDの基礎と臨床.

    Tandem Lecture Series on Blood Disease Treatment -HSCT・GVHD-  2012 

     More details

  • 縦隔原発悪性リンパ腫に対しRituximab併用DA-EPOCH療法を施行した2症例

    第52回日本リンパ網内系学会総会  2012 

     More details

  • 同種造血幹細胞移植後心合併症に影響を与える因子-多様な幹細胞ソースによる172例の解析-; Affect of cardiac complications after Allogeneic Hematopoietic Stem Cell Transplantation from various stem cell sources

    第34回日本造血細胞移植学会総会  2012 

     More details

  • 再生不良性貧血の同種末梢血幹細胞植後にドナー細胞由来の骨髄異形成候群を発症した1例

    第51回日本血液学会中国四国地方会  2012 

     More details

  • HLA半合致同種造血幹細胞移植後に移植片対宿主病として脱髄性多発神経炎所見を呈した1例; A case of chronic inflammatory demyelinating polyneuropathy(CIDP)accompanied with graft versus host disease after HLA haplo-identical hematopoietic stem cell transplantation

    第34回日本造血細胞移植学会総会  2012 

     More details

  • 悪性リンパ腫に対する臍帯血移植23例の検討

    第51回日本リンパ網内系学会総会  2011 

     More details

  • 顆粒リンパ球増多症と慢性活動性EBウイルス感染症から節外性NK/T細胞リンパ腫,鼻型を発症した1例

    第104回日本内科学会中国地方会  2011 

     More details

  • 半合致同種造血幹細胞移植後に移植片対宿主病として慢性炎症性脱髄性多発神経炎を呈した1例

    第50回日本血液学会中国四国地方会  2011 

     More details

  • 頭蓋内病変により急激な意識障害を合併した精巣原発形質細胞腫瘍の1例

    第50回日本血液学会中国四国地方会  2011 

     More details

  • 伝染性単核球症を初発症状として発症したPrimary-HIV-1 Infectionの1例

    第104回日本内科学会中国地方会  2011 

     More details

  • 頭蓋内病変により急激な意識障害を合併した精巣原発形質細胞腫瘍の1例

    第12回中四リンパ腫カンファレンス  2011 

     More details

  • 中枢神経系悪性リンパ腫に対する自己末梢血幹細胞移植併用大量化学療法

    第33回日本造血細胞移植学会総会  2011 

     More details

  • 医歯看連携による組織的な口腔内管理は造血細胞移植患者の口腔粘膜障害を減少させる

    第33回日本造血細胞移植学会総会  2011 

     More details

  • 非血縁骨髄移植2年後に、下肢深部静脈血栓症と脳梗塞を発症したMDSの1例

    第50回日本血液学会中国四国地方会  2011 

     More details

  • 生体肝移植後にAPLを発症し、ATRA、亜ヒ酸にて治療した1例

    第50回日本血液学会中国四国地方会  2011 

     More details

  • 骨髄非破壊的前処置法FLU/CY/TBIおよび面積抑制薬CSA/低用量MMFを用いた臍帯血移植の前方視的研究-第2報

    第33回日本造血細胞移植学会総会  2011 

     More details

  • ドナーのTh17細胞とTh1細胞が慢性GVHD発症に関与する

    第33回日本造血細胞移植学会総会  2011 

     More details

  • 同種造血細胞移植後のBronchiolitis Obliterans Syndrome BOS-Okayama BMT Group OBMTG 3施設での経験-

    第33回日本造血細胞移植学会総会  2011 

     More details

  • Affect of cardiac complications after allogeneic hematopoietic stem cell transplantation from various cell sources

    2011 BMT Tandem Meetings  2011 

     More details

  • Bronchiolitis obliterans syndrome afer hematopoietic stem cell transplantation: Analysis of single center experience

    2011 BMT Tandem Meetings  2011 

     More details

  • 多様な幹細胞ソースによる同種造血幹細胞移植244例におけるGVHD発症と移植成績の検討

    第33回日本造血細胞移植学会総会  2011 

     More details

  • Prevention of idiopathic pneumonia syndrome by intra-bone marrow injection of donor cells

    2011 BMT Tandem Meetings  2011 

     More details

  • Affect of cardiac complications after allogeneic hematopoietic stem cell transplantation from various cell sources

    2011 BMT Tandem Meetings  2011 

     More details

  • Donor Th17 and Th1 contribute to chronic graft-versus-host disease

    2011 BMT Tandem Meetings  2011 

     More details

  • Donor Th17 and Th1 contribute to chronic graft-versus-host disease

    2011 BMT Tandem Meetings  2011 

     More details

  • Prevention of idiopathic pneumonia syndrome by intra-bone marrow injection of donor cells

    2011 BMT Tandem Meetings  2011 

     More details

  • 中枢神経系悪性リンパ腫に対する自己末梢血幹細胞移植併用大量化学療法

    第73回日本血液学会学術集会  2011 

     More details

  • 同種造血細胞移植後の閉塞性細気管支炎-岡山BMTグループ3施設での経験-

    第73回日本血液学会学術集会  2011 

     More details

  • Prevention of idiopathic pneumonia syndrome by intra-bone marrow injection of donor cells

    53rd ASH Annual Meeting  2011 

     More details

  • Results of haploidentical SCT in refractory hematological malignancies at a single institute

    第73回日本血液学会学術集会  2011 

     More details

  • Prevention of idiopathic pneumonia syndrome by intra-bone marrow injection of donor cells

    第73回日本血液学会学術集会  2011 

     More details

  • Efficacy of biweekly R-CHOP followed by auto-PBSCT for DLBCL: JSCT Multicenter Study JSCT-NHL04

    第73回日本血液学会学術集会  2011 

     More details

  • Blood stream infections in early phase of allogenic hematopoietic stem cell transplantation

    第73回日本血液学会学術集会  2011 

     More details

  • 中枢神経系悪性リンパ腫に対する自己末梢血幹細胞移植併用大量化学療法

    第51回日本リンパ網内系学会総会  2011 

     More details

  • 血管免疫芽球性T細胞リンパ腫の多施設共同後方視的研究

    第50回日本リンパ網内系学会総会  2010 

     More details

  • Donor Th17 and Th1 contribute to chronic graft-versus-host disease

    52nd ASH Annual Meeting  2010 

     More details

  • Utility of positron emission tomography/computed tomography in extranodal natural killer/T-cell lymphoma

    52nd ASH Annual Meeting  2010 

     More details

  • Pretreatment EBV-DNA copy number is predictive for response to SMILE chemotherapy for newly-diagnosed stage IV, relapsed or refractory extranodal NK/T-cell lymphoma, nasal type: results of NKTSG phase II stady

    52nd ASH Annual Meeting  2010 

     More details

  • Prospective multicenter phase II of study of myeloablative conditioning consisted of intravenous busulfan and fludarabine +/- total body irradiation for older patients (55 years and older): results of the JSCT FB09 study

    52nd ASH Annual Meeting  2010 

     More details

  • Phase II study of SMILE for fresh stage IV, reapsed or refractory extranodal NK/T-cell lymphoma

    第72回日本血液学会学術集会  2010 

     More details

  • The impact of HCV infection on outcome and hepatic toxicity in DLBCL in rituximab era

    第72回日本血液学会学術集会  2010 

     More details

  • Synthetic retinoid Am80 ameliorates chronic Graft-Versus-Host Disease via Th1/Th17 cell regulation

    第72回日本血液学会学術集会  2010 

     More details

  • A clinicopathological analysis of angioimmunoblastic T-cell lymphoma

    第72回日本血液学会学術集会  2010 

     More details

  • Clinical outcomes of umbilical cord blood transplantation for 63 adults

    第72回日本血液学会学術集会  2010 

     More details

  • Impact of pre-transplant serum ferritin on outcomes of patients receiving allogeneic HSCT

    第72回日本血液学会学術集会  2010 

     More details

  • 劇症肝炎を発症し, 同種造血幹細胞移植を施行したEBV関連NK/T細胞増殖症の2例

    第50回日本リンパ網内系学会総会  2010 

     More details

  • 多臓器に浸潤を呈したT細胞性顆粒リンパ球増多症の1例

    第102回日本内科学会中国地方会  2010 

     More details

  • T細胞前リンパ性白血病の1例

    第102回日本内科学会中国地方会  2010 

     More details

  • 肺, 脾臓, 全身リンパ節に浸潤を呈したT細胞性顆粒リンパ球増多症の1例

    第50回日本リンパ網内系学会総会  2010 

     More details

  • 同種造血幹細胞移植後の制御性T細胞再構築

    森島班 班会議  2009 

     More details

  • 再発もしくは治療抵抗性末梢T細胞性リンパ腫に対する減量強度移植前処置を用いた 同種造血幹細胞移植の有効性に関する 臨床第II相試験

    第24回悪性リンパ腫治療研究会  2009 

     More details

  • マウスモデルを使った造血幹細胞の 静脈内と骨髄内輸注法の比較

    造血細胞移植合同班会議 新しい造血幹細胞移植技術の開発に関する研究班  2009 

     More details

  • 造血幹細胞移植症例におけるMicafunginとFluconazole予防投与の比較試験

    日本造血細胞移植学会  2008 

     More details

  • Prediction of minimum number of aphaeresis procedures for healthy donor of peripheral blood stem cells using ordinal probit regression analysis

    アメリカ血液学会  2008 

     More details

  • 同種造血幹細胞移植後再発・生着不全に対する再移植

    第6回日本臨床腫瘍学会  2008 

     More details

  • 当科における同種骨髄非破壊的移植(RIST)の治療成績

    日本造血細胞移植学会  2008 

     More details

  • 同種末梢血幹細胞ドナーが要するアフェレーシス回数の予測

    日本造血幹細胞移植学会  2008 

     More details

  • Cyclosporine, but not mTOR inhibitors, hampers the reconstitution of bone marrow-derived Tregs in long-term complete donor chimeras

    アメリカ血液学会  2008 

     More details

  • 西日本血液腫瘍研究グループ (West-JHOG)における多施設共同研究の試み

    第69回 日本血液学会 第49回 日本臨床血液学会  2007 

     More details

  • 人工肛門造説後に骨髄非破壊的移植を施行した急性骨髄性白血病の1例

    第46回日本血液学会中国四国地方会  2007 

     More details

  • 進行期低悪性度リンパ腫に対する骨髄非破壊的同種造血幹細胞移植

    日本造血幹細胞移植学会  2007 

     More details

  • 移植方法(骨髄破壊的同種移植・骨髄非破壊的同種移植及び自家移植)と口腔粘膜障害の重症度との関連性に関する研究

    日本造血幹細胞移植学会  2007 

     More details

  • 同種骨髄移植後に意識障害を呈した1例

    第46回日本血液学会中国四国地方会教育セミナー  2007 

     More details

  • 皮膚顆粒球肉腫を伴う高齢者骨髄異形成症症候群に対し、臍帯血RISTが有効であった1例

    日本造血幹細胞移植学会  2007 

     More details

  • 同種造血幹細胞移植後の移植片対白血病効果における抗原提示細胞と同種抗原の役割

    第29回 日本造血幹細胞移植学会  2007 

     More details

  • 非血縁者間同種骨髄移植後の閉塞性細気管支炎に肺アスペルギルス症を合併した一例

    第3回岡山院内感染対策フォーラム  2006 

     More details

  • Homeostatic proliferationしたT細胞は、同種骨髄移植後におこる急性移植片対宿主病の誘導能が低下する

    第25回岡山免疫懇話会  2006 

     More details

  • GVHD と GVL における抗原提示細胞と同種抗原の役割

    日本造血幹細胞移植学会  2006 

     More details

  • 皮膚顆粒球肉腫を伴う高齢者骨髄異形成症症候群に対し、臍帯血RISTが有効であった1例

    第95回日本内科学会中国地方会  2006 

     More details

  • Homeostatic proliferationしたT細胞による急性移植片対宿主病誘導能の検討

    第68回 日本血液学会 第48回 日本臨床血液学会  2006 

     More details

  • 臍帯血移植後に播種性トリコスポロン症を発症した一例

    第13回深在性真菌症岡山フォーラム  2006 

     More details

  • 後天性血友病(第8因子インヒビター)として治療経過中にヘパリン自己注射が判明した1例

    第94回日本内科学会中国地方会  2006 

     More details

  • 当院におけるAML/MDSに対する骨髄非破壊的同種造血幹細胞移植の検討

    第6回Okayama Hematology Conference  2006 

     More details

  • 再発・治療抵抗性非ホジキンリンパ腫に対するGIDEA療法の有効性と安全性の検討

    第20回岡山造血幹細胞移植研究会  2006 

     More details

  • 発熱と汎血球減少症の軽快と再燃を繰り返す69歳の女性

    第4回日本血液学会中国四国地方会教育セミナー  2006 

     More details

  • 発熱で発症し診断に苦慮したIVLの一例

    第2回中四リンパ腫カンファレンス  2006 

     More details

  • 非血縁者間骨髄移植後の生着不全に対し臍帯血ミニ移植で造血回復に成功したPh ALLの一例

    第12回中国・四国造血幹細胞移植研究会  2006 

     More details

  • Histone deacetylase inhibitors induce immuno-dominant suppression of dendritic cells

    アメリカ血液学会  2005 

     More details

  • 顆粒リンパ球増加症(granular lymphocyte-proliferative disorders)の1例

    第93回日本内科学会中国地方会  2005 

     More details

  • 無顆粒球症に対してサイクロスポリン療法が有効であった低ガンマグロブリン血症を合併した胸腺腫(Good症候群)

    第93回日本内科学会中国地方会  2005 

     More details

  • 非血縁者間同種骨髄移植後のBronchiolitis obliteranceに合併した肺アスペルギルス症にボリコナゾールが奏功した1例

    第2回岡山感染症の集い  2005 

     More details

  • 発熱と汎血球減少症の自然軽快と再燃を繰り返して発症したリンパ腫の1例

    第1回中国リンパ腫カンファレンス  2005 

     More details

  • 肺・胃それぞれにMALT(mucosa-associated lymphoid tissue)リンパ腫と肺癌の合併を認めた1例

    第93回日本内科学会中国地方会  2005 

     More details

  • 皮下腫瘤と甲状腺腫瘤にんて発症したびまん性大細胞型B細胞性リンパ腫の1例

    第93回日本内科学会中国地方会  2005 

     More details

  • 進行期低悪性度リンパ腫に対する骨髄非破壊的同種造血幹細胞移植(RIST)

    第67回日本血液学会 第47回日本臨床血液学会  2005 

     More details

  • 造血幹細胞移植におけるGVHDとアポトーシス

    第14回日本アポトーシス研究会学術集会  2005 

     More details

  • 非血縁者間同種骨髄移植後の閉塞性細気管支炎に肺アスペルギルス症を合併した一例

    第71回岡山最新医学セミナー  2005 

     More details

  • 非小細胞肺癌に対するGefitinib治療中の急性前骨髄球性白血病の発症

    第67回日本血液学会 第47回日本臨床血液学会  2005 

     More details

  • 進行期低悪性度リンパ腫に対する骨髄非破壊的同種造血幹細胞移植(RIST)

    第67回日本血液学会・第47回日本臨床血液学会  2005 

     More details

  • 成人大脳型副腎白質ジストロフィーに非骨髄破壊的前治療による同種骨髄幹細胞移植を施行した一例

    第19回岡山造血幹細胞移植研究会  2005 

     More details

  • 低悪性度リンパ腫に対する骨髄非破壊的同種造血幹細胞移植(RIST)の成績

    第11回中国・四国骨髄移植研究会  2005 

     More details

  • 慢性骨髄性白血病急性転化に対する臍帯血移植後にトリコスポロン敗血症を呈した一例

    第71回岡山最新医学セミナー  2005 

     More details

  • 低悪性度リンパ腫に対する骨髄非破壊的同種造血幹細胞移植(RIST)の成績

    第45回日本リンパ網内系学会総会  2005 

     More details

  • グリベック単独療法を行った慢性骨髄性白血病のリンパ性急性転化の1例

    第44回日本血液学会中国地方会教育セミナー  2005 

     More details

  • Suberoylanilide hydroxamic acid modulates the innate and allostimulatory responses of dendritic cells and regulates experimental acute graft-versus-host disease

    アメリカ造血幹細胞移植学会  2005 

     More details

  • Host gamma d T cells exacerbate experimental acute graft-versus-host disease through activation of host antigen presenting cells.

    アメリカ血液学会  2004 

     More details

  • Perforin and Fas ligand are required for the regulation of alloreactive CD8(+) T cells

    アメリカ血液学会  2004 

     More details

  • Suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect by inhibiting histone deacetylation

    アメリカ造血幹細胞移植学会  2004 

     More details

  • Allo-antigen expression on both APCS and tumor is required to elicit an effective GVL response after experimental allogeneic BMT.

    アメリカ血液学会  2004 

     More details

  • Differential effects of IL-18 on the severity of acute graft-versus-host disease mediated by CD4(+) and CD8(+) T cell subsets after experimental allogeneic bone marrow transplantation.

    アメリカ血液学会  2003 

     More details

  • Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect after experimental bone marrow transplantation.

    アメリカ血液学会  2003 

     More details

  • Host gamma d T cells exacerbate acute GVHD by enhancing the allostimulatory capacity of host APCs.

    アメリカ血液学会  2003 

     More details

  • Differential effects of IL-18 on the severity of acute graft-versus-host disease mediated by CD4(+) and CD8(+) T cell subsets after experimental allogeneic bone marrow transplantation.

    アメリカ血液学会  2002 

     More details

▼display all

 

Class subject in charge

  • Advanced Hospital Practice (2021academic year) Prophase  - その他

  • Internal Medicine (2021academic year) 1st and 2nd semester  - [第1学期]月4,月5,水6, [第2学期]月4,月5,金6

  • Respiratory Medicine (2021academic year) special  - その他

  • Research Presentation in Clinical Trial (2021academic year) special  - その他

  • Internal Medicine (2)(Core Clinical Practice) (2021academic year) special  - その他

  • Research Projects and Practicals: Hematology, Oncology and Respiratory Medicine I (2021academic year) special  - その他

  • Lecture and Research Projects: Hematology, Oncology and Respiratory Medicine I (2021academic year) special  - その他

  • Research Projects and Practicals: Hematology, Oncology and Respiratory Medicine II (2021academic year) special  - その他

  • Lecture and Research Projects: Hematology, Oncology and Respiratory Medicine II (2021academic year) special  - その他

  • Hematology (2021academic year) special  - その他

  • Elective Clinical Practice (Internal Medicine (2)) (2021academic year) special  - その他

  • Internal Medicine (2020academic year) 1st and 2nd semester  - [第1学期]月4,月5,水6, [第2学期]月4,月5,金6

  • Respiratory Medicine (2020academic year) special  - その他

  • Research Presentation in Clinical Trial (2020academic year) Year-round  - その他

  • Clinical Trial (2020academic year) Year-round  - その他

  • Internal Medicine (2)(Core Clinical Practice) (2020academic year) special  - その他

  • Research Projects and Practicals: Hematology, Oncology and Respiratory Medicine I (2020academic year) special  - その他

  • Lecture and Research Projects: Hematology, Oncology and Respiratory Medicine I (2020academic year) special  - その他

  • Research Projects and Practicals: Hematology, Oncology and Respiratory Medicine II (2020academic year) special  - その他

  • Lecture and Research Projects: Hematology, Oncology and Respiratory Medicine II (2020academic year) special  - その他

  • Hematology (2020academic year) special  - その他

  • Elective Clinical Practice (Internal Medicine (2)) (2020academic year) special  - その他

▼display all