Faculty Profiles - MAEDA Yoshinobu

免疫チェックポイント阻害薬投与によりがん性疼痛の著しい悪化を認めた一例

市原英基, 渡邉洋美, 二宮崇, 原尚史, 二宮貴一郎, 久保寿夫, 大橋圭明, 堀田勝幸, 田端雅弘, 前田嘉信, 木浦勝行

Palliative Care Research (Web) 13 ( Supplement ) 2018

Unusual oral mucosal microbiota after hematopoietic cell transplantation with glycopeptide antibiotics: potential association with pathophysiology of oral mucositis. International journal

Misato Muro, Yoshihiko Soga, Tomoko Higuchi, Kota Kataoka, Daisuke Ekuni, Yoshinobu Maeda, Manabu Morita

Folia microbiologica 63 ( 5 ) 587 - 597 2018

Language：English

Severe oral mucositis occurs frequently in patients receiving hematopoietic stem cell transplantation (HCT). Oral mucosal bacteria can be associated with progression of oral mucositis, and systemic infection may occur via ulcerative oral mucositis. However, little information is available regarding the oral microbiota after HCT. Here, PCR-denaturing gradient gel electrophoresis (DGGE) was performed to characterize the oral mucosal microbiota, which can be affected by antibiotics, before and after HCT. Sixty reduced-intensity HCT patients were enrolled. Three patients with the least antibiotic use (quinolone prophylaxis and/or β-lactam monotherapy group) and three patients with the most antibiotic use (β-lactam-glycopeptide combination therapy group) were selected. Bacterial DNA samples obtained from the oral mucosa before and after HCT were subjected to PCR-DGGE. The trajectory of oral mucositis was evaluated. The oral mucosal microbiota in the β-lactam-glycopeptide combination therapy group was different from that in the quinolone prophylaxis and/or β-lactam monotherapy group, and Staphylococcus spp. and Enterococcus spp. were identified. Lautropia mirabilis was dominant in one patient. Ulcerative oral mucositis was observed only in the β-lactam-glycopeptide combination therapy group. In conclusion, especially with the use of strong antibiotics, such as glycopeptides, the oral mucosal microbiota differed completely from that under normal conditions and consisted of Staphylococcus spp., Enterococcus spp., and unexpectedly L. mirabilis. The normal oral microbiota consists not only of bacteria, but these unexpected bacteria could be involved in the pathophysiology as well as systemic infection via oral mucositis. Our results can be used as the basis for future studies in larger patient populations.

DOI： 10.1007/s12223-018-0596-1

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

岡本幸代, 松岡賢市, 坂本真衣子, 碓井喜明, 藤原悠紀, 近藤匠, 松田真幸, 谷勝真, 佐伯恭昌, 廻勇輔, 淺田騰, 西森久和, 藤井伸治, 近藤英生, 前田嘉信

日本造血細胞移植学会総会プログラム・抄録集 40th 336 2017.12

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

坂本真衣子, 廻勇輔, 松田真幸, 碓井喜明, 近藤匠, 佐伯恭昌, 淺田騰, 西森久和, 松岡賢市, 藤井伸治, 近藤英生, 森原隆太, 山本晃, 木口亨, 前田嘉信

日本造血細胞移植学会総会プログラム・抄録集 40th 338 2017.12

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

碓井喜明, 淺田騰, 近藤匠, 松田真幸, 坂本真衣子, 谷勝真, 藤原悠紀, 佐伯恭昌, 廻勇輔, 岡本幸代, 西森久和, 松岡賢市, 藤井伸治, 近藤英生, 前田嘉信

日本造血細胞移植学会総会プログラム・抄録集 40th 220 2017.12

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

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

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

HAEMATOLOGICA 102 ( 12 ) 2097 - 2103 2017.12

Language：English Publisher：FERRATA STORTI FOUNDATION

DOI： 10.3324/haematol.2017.167742

Granulocyte Transfusions for Neutropenic Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

Shuntaro Ikegawa, Nobuharu Fujii, Keiko Fujii, Yusuke Meguri, Kyosuke Saeki, Noboru Asada, Hisakazu Nishimori, Ken-ichi Matsuoka, Yoshinobu Maeda

BLOOD 130 2017.12

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

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

CANCER SCIENCE 108 ( 10 ) 2061 - 2068 2017.10

Language：English Publisher：WILEY

Pralatrexate is a novel antifolate approved in the USA for the treatment of relapsed or refractory peripheral T-cell lymphoma. To assess its safety, efficacy, and pharmacokinetics in Japanese patients with this disease, we undertook a phase I/II study. Pralatrexate was given i.v. weekly for 6weeks of a 7-week cycle. All patients received concurrent vitamin B-12 and folic acid. In phase I, three patients received pralatrexate 30mg/m(2) and none experienced a dose-limiting toxicity. In phase II, we treated 22 additional patients with that dose. The median number of treatment cycles was 1 (range, 1-9). Nine of 20 evaluable patients (45%) achieved an objective response by central review, including two complete responses. All responses occurred within the first treatment cycle. At the time of data cut-off, median progression-free survival was 150days. Median overall survival was not reached. In the total population, the most commonly reported adverse events included mucositis (88%), thrombocytopenia (68%), liver function test abnormality (64%), anemia (60%), and lymphopenia (56%). Grade 3/4 adverse events included lymphopenia (52%), thrombocytopenia (40%), leukopenia (28%), neutropenia (24%), anemia (20%), and mucositis (20%). The pharmacokinetic profile showed no drug accumulation with repeat dosing. These results indicate that pralatrexate is generally well tolerated and effective in Japanese patients with relapsed or refractory peripheral T-cell lymphoma. This trial was registered with ClinicalTrials.gov (NCT02013362).

DOI： 10.1111/cas.13340

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

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

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

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

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

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

Language：English Publisher：WILEY

DOI： 10.1111/his.13223