Updated on 2025/04/02

写真a

 
KONDO Takumi
 
Organization
Scheduled update Assistant Professor
Position
Assistant Professor
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Research History

  • Okayama University Hospital   Hematology   Assistant Professor

    2024.10

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  • Kochi University   Hematology   Lecturer

    2023.11 - 2024.3

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  • Kochi University   Hematology   Assistant Professor

    2022.9 - 2023.10

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  • Okayama University   Hematology and Oncology   Assistant Professor

    2022.4 - 2022.9

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Papers

  • Markedly elevated serum level of presepsin in agranulocytosis with hematologic malignancy: A potential prognostic factor in a single-institution retrospective study after granulocyte transfusion. International journal

    Takuya Fukumi, Keiko Fujii, Wataru Kitamura, Kazuhiro Ikeuchi, Naomi Asano, Akira Yamamoto, Hiroki Kobayashi, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Ken-Ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda, Nobuharu Fujii

    Laboratory medicine   2025.3

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    Language:English   Publishing type:Research paper (scientific journal)  

    INTRODUCTION: No established criteria exist for assessing the effectiveness of granulocyte transfusion (GTX) or biomarkers for predicting fatal infections in neutropenia. This study aimed to assess whether a novel sepsis marker, presepsin (P-SEP), is a useful prognostic indicator during GTX. METHODS: We collected frozen serum from 8 patients who had undergone GTX between September 2022 and October 2023 and measured their P-SEP levels. We compared these results with clinical records and assessed the alterations before and after GTX and their association with prognosis. RESULTS: The post-transfusion neutrophil count increased in all cases. In 5 of 8 patients (62.5%), P-SEP levels were reduced 1 day after GTX. Pretransfusion P-SEP levels were statistically significantly lower in the group of patients who survived and overcame infection after transfusion (GTX-survived) than in the group of patients who did not survive (GTX-nonsurvived) (1493 pg/mL vs 6658 pg/mL, P =.04). Transfused cell counts and changes in P-SEP levels 1 day after GTX were better in the GTX-survived group than in the GTX-nonsurvived group, although the difference was not statistically significant. DISCUSSION: Presepsin is a biomarker that can be assessed in patients undergoing GTX for agranulocytosis. A clinically significant increase in P-SEP levels before GTX may indicate ineffective GTX and an unfavorable prognosis.

    DOI: 10.1093/labmed/lmae118

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  • A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD. International journal

    Wataru Kitamura, Keiko Fujii, Mitsuru Tsuge, Toshiharu Mitsuhashi, Hiroki Kobayashi, Chihiro Kamoi, Akira Yamamoto, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Ken-Ichi Matsuoka, Nobuharu Fujii, Yoshinobu Maeda

    Annals of hematology   2025.2

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    Therapies that effectively suppress graft-versus-host disease (GVHD) without compromising graft-versus-leukemia/lymphoma (GVL) effects is important in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic malignancies. Geranylgeranylacetone (GGA) is a main component of teprenone, a gastric mucosal protectant commonly used in clinical practice. In preclinical models, GGA suppresses proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), which are associated with GVHD as well as induces thioredoxin-1 (Trx-1), which suppresses GVHD while maintaining GVL effects. Here, we investigated whether the addition of teprenone to standard GVHD prophylaxis could reduce the cumulative incidence of severe acute GVHD (aGVHD) without attenuating GVL effects. This open-label, randomized clinical trial enrolled 40 patients (21 control and 19 teprenone group) who received allo-HSCT between May 2022 and February 2023 in our institution. Patients in the teprenone group received 50 mg of teprenone orally thrice daily for 21 days from the initiation of the conditioning regimen. The cumulative incidence of severe aGVHD by day 100 after allo-HSCT was not significantly different in the two groups (27.9 vs. 16.1%, p = 0.25). The exploratory studies revealed no obvious changes in Trx-1 levels, but the alternations from baseline in IL-1β and TNF-α levels at day 28 after allo-HSCT tended to be lower in the teprenone group. In conclusion, we could not demonstrate that teprenone significantly prevented the development of severe aGVHD. Discrepancy with preclinical model suggests that appropriate dose of teprenone may be necessary to induce the expression of antioxidant enzymes that suppress severe aGVHD. Clinical Trial Registration number:jRCTs 061210072.

    DOI: 10.1007/s00277-025-06269-2

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  • Myelodysplastic neoplasms with repeating TAFRO syndrome-like symptoms.

    Kenta Hayashino, Nobuharu Fujii, Tomohiro Nagano, Daisuke Ikeda, Kanako Fujiwara, Risa Hashida, Wataru Kitamura, Hiroki Kobayashi, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

    International journal of hematology   2025.2

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    TAFRO syndrome is a systemic disease characterized by thrombocytopenia, anasarca, fever, systemic inflammation, reticulin fibrosis, renal insufficiency, and organomegaly. Although the pathogenesis of TAFRO syndrome remains unknown, it may be associated with cytokine storm and abnormal immune function. Herein, we present a case of a 65-year-old man who was diagnosed with myelodysplastic neoplasms (MDS) with repeating TAFRO syndrome-like symptoms. At ages 59 and 63 years, he developed TAFRO syndrome and was treated with immunosuppressive therapy, which improved these symptoms. At age 65 years, he had TAFRO syndrome-like symptoms with pancytopenia, chromosomal abnormalities, and dysplasia. The patient was subsequently diagnosed with MDS and treated with methylprednisolone, rituximab, bortezomib, and tocilizumab. His MDS-related and TAFRO syndrome-like symptoms simultaneously improved following treatment. Although the patient was not diagnosed with MDS at the first and second events, chromosomal abnormalities were detected, revealing increased clonal cells. MDS can be complicated by immune disorders associated with increased malignant clonal cells. Additionally, patients with MDS exhibit hypercytokinemia, including interleukin-6 and vascular endothelial growth factor. This case indicates that increased clonal cells and hypercytokinemia caused by MDS may lead to abnormal immune function and induce TAFRO syndrome-like symptoms.

    DOI: 10.1007/s12185-025-03937-x

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  • A fatal case of enterovirus A71-induced meningoencephalitis following allogenic hematopoietic stem cell transplantation. International journal

    Yayoi Ueda, Hiroki Kobayashi, Hideaki Fujiwara, Hideharu Hagiya, Risa Hashida, Saya Kubota, Mami Takemoto, Kenta Hayashino, Kanako Fujiwara, Tomohiro Nagano, Ryuichiro Hiyama, Keiko Fujii, Takumi Kondo, Keisuke Seike, Noboru Asada, Daisuke Ennishi, Nobuharu Fujii, Ken-Ichi Matsuoka, Maeda Yoshinobu

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   31 ( 4 )   102630 - 102630   2025.1

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    Enterovirus A71 (EV-A71) is a major pathogen responsible for hand, foot, and mouth disease (HFMD) in infants and children. EV-A71 infection represents an epidemic in the Asia-Pacific region, and can cause serious central nervous system (CNS) infections in immunocompromised patients that can result in paralysis, disability, or death. There have been few reports in the literature concerning EV-A71 CNS infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult patients. We describe the case of a 63-year-old woman with EV-A71 meningoencephalitis who underwent a second allo-HSCT for relapsed refractory myelodysplastic syndrome. She developed disturbance of consciousness during intubation due to severe pulmonary impairment following allo-HSCT. Despite the absence of pleocytosis in the cerebrospinal fluid, enterovirus was detected in her cerebral spinal fluid using the Biofire® FilmArray® Meningitis/Encephalitis (ME) panel, which was later identified as EV-A71 at a referral center. Despite a transient improvement in her level of consciousness after intravenous immunoglobulin administration, she did not fully recover. The patient also showed muscle weakness as well as pulmonary impairment that necessitated a tracheotomy. Our case demonstrated the utility of the FilmArray® ME panel as a screening tool for detecting multiple potential pathogens until a specific pathogen could be identified using other diagnostic methods. Clinicians should be aware that EV-A71 CNS infection can occur among adults with severe immunodeficient conditions, and that it leads poor clinical outcomes. Our case suggests that continuous monitoring for this potentially fatal pathogen is warranted for immunocompromised patients.

    DOI: 10.1016/j.jiac.2025.102630

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  • Severe hypophosphatemia following idecabtagene vicleucel regardless of the severity of cytokine release syndrome

    Kenta Hayashino, Wataru Kitamura, Nobuharu Fujii, Toshiki Terao, Hiroki Kobayashi, Chihiro Kamoi, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Yoshinobu Maeda

    Cytotherapy   2025.1

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    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.jcyt.2024.12.014

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  • [Treatment outcomes of axicabtagene ciloleucel for relapsed/refractory diffuse large B-cell lymphoma: a retrospective analysis at a single institution].

    Wataru Kitamura, Nobuharu Fujii, Chihiro Kamoi, Toshiki Terao, Akira Yamamoto, Hiroki Kobayashi, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Keiko Fujii, Noboru Asada, Daisuke Ennishi, Yoshinobu Maeda

    [Rinsho ketsueki] The Japanese journal of clinical hematology   66 ( 2 )   81 - 91   2025

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    The advent of anti-CD19 chimeric antigen receptor-T cell therapy has dramatically changed the treatment strategy for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Three products are recently available in Japan, but to the best of our knowledge, real-world data are only available for tisagenlecleucel. This study was a retrospective analysis of 27 patients who received axicabtagene ciloleucel (axi-cel) for R/R DLBCL at our institution. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 24 (88.9%) and 8 patients (29.6%), respectively, and corticosteroids were used in 19 patients (70.4%). The median follow-up period was 8.1 months (range, 1.0-23.2), and the 6-month progression-free survival and overall survival rates were 80.2% (95% confidence interval [CI], 58.8-91.3) and 92.0% (95%CI, 71.6-97.9), respectively. Although our study was limited by its small sample size and short follow-up period, it demonstrated that axi-cel was highly effective and safe at our institution.

    DOI: 10.11406/rinketsu.66.81

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  • Oral calcium supplementation versus placebo in mitigating citrate reactions during apheresis: an open-label randomized control trial

    Masaya Abe, Keiko Fujii, Nobuharu Fujii, Toshiharu Mitsuhashi, Takuya Fukumi, Yuichi Sumii, Maiko Kimura, Tomohiro Urata, Takumi Kondo, Fumio Otsuka, Yoshinobu Maeda

    Hematology, Transfusion and Cell Therapy   2024.12

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    DOI: 10.1016/j.htct.2024.06.010

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  • Development of disseminated intravascular coagulation in asymptomatic leukemic non-nodal mantle cell lymphoma

    Takumi Kondo, Keito Ohara, Shohei Yoshida, Kensuke Kojima

    Annals of Hematology   2024.8

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    DOI: 10.1007/s00277-024-05727-7

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  • Combination of reduced post‐transplant cyclophosphamide and early tacrolimus initiation increases the incidence of chronic graft‐versus‐host disease in human leukocyte antigen‐haploidentical peripheral blood stem‐cell transplantation

    Toshiki Terao, Takumi Kondo, Makoto Nakamura, Hiroki Takasuka, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Yoshinobu Maeda, Ken‐ichi Matsuoka

    eJHaem   2024.6

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    Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    Abstract

    We evaluated the clinical impacts of the concurrent modification of post‐transplant cyclophosphamide (PTCy) dose and tacrolimus (Tac)‐initiation timing in 61 patients with human leukocyte antigen‐haploidentical transplantation. Reduced‐dose PTCy (80 mg/kg) was associated with a higher incidence of moderate‐to‐severe chronic graft‐versus‐host disease (GVHD) than standard‐dose PTCy (100 mg/kg) (35.0% vs. 26.6%, p = 0.053). Notably, early‐initiation Tac (day ‐1) increased moderate‐to‐severe chronic GVHD than standard‐initiation Tac (day 5) in the reduced‐dose PTCy group (p = 0.032), whereas Tac‐initiation timing did not impact chronic GVHD in the standard‐dose PTCy group. These data indicate that the combination of reduced‐dose PTCy and early‐initiation Tac can amplify chronic GVHD.

    DOI: 10.1002/jha2.962

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  • Novel Four-Way t(8;14;15;21)(q22;q22;q15;q22.1) Translocation Variant in Acute Myeloid Leukemia with RUNX1: : RUNX1T1

    Noriko Tsuge, Fumiya Ogasawara, Takumi Kondo, Shohei Yoshida, Kensuke Kojima

    Turkish Journal of Hematology   2024.5

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    DOI: 10.4274/tjh.galenos.2024.2024.0038

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  • Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK‐rearranged non‐small cell lung cancer

    Chihiro Ando, Eiki Ichihara, Tatsuya Nishi, Ayako Morita, Naofumi Hara, Kenji Takada, Takamasa Nakasuka, Hiromi Watanabe, Hirohisa Kano, Kazuya Nishii, Go Makimoto, Takumi Kondo, Kiichiro Ninomiya, Masanori Fujii, Toshio Kubo, Kadoaki Ohashi, Ken‐ichi Matsuoka, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Cancer Science   2023.11

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    <jats:title>Abstract</jats:title><jats:p>Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3‐mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against <jats:italic>ALK</jats:italic>‐rearranged non‐small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several <jats:italic>ALK</jats:italic>‐rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several <jats:italic>ALK</jats:italic>‐rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal–epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib‐treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of <jats:italic>ALK</jats:italic>‐rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin‐15 (IL‐15) mRNA levels were elevated in gilteritinib‐treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL‐15 production along with NK cell infiltration may constitute components of the gilteritinib‐mediated antitumor responses in <jats:italic>ALK</jats:italic>‐rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against <jats:italic>ALK</jats:italic>‐rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings.</jats:p>

    DOI: 10.1111/cas.15958

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  • Evaluating the efficiency and safety of large-volume leukapheresis using the Spectra Optia continuous mononuclear cell collection protocol for peripheral blood stem cell collection from healthy donors: A retrospective study. International journal

    Yuichi Sumii, Keiko Fujii, Takumi Kondo, Tomohiro Urata, Maiko Kimura, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-Ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda, Nobuharu Fujii

    Transfusion   2023.10

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    BACKGROUND: Large-volume leukapheresis (LVL) refers to processing of more than three volumes of blood in a single session for peripheral blood stem cell collection. Recently, continuous mononuclear cell collection (cMNC) protocol has been developed using the Spectra Optia system, which is a widely used apheresis device. LVL using the novel protocol has been investigated in patients. However, the efficiency and safety of LVL in healthy donors using this protocol has not been characterized. Therefore, this study aimed to evaluate the efficiency and tolerability of CD34+ collection of LVL with the cMNC protocol in healthy donors. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (>3 total blood volume) and normal-volume leukapheresis (NVL) performed in healthy donors between October 2019 and December 2021. All procedures were performed using the cMNC protocol. RESULTS: Although pre-apheresis CD34+ cell count was lesser in LVL (23.5 vs. 58.0/μL, p < .001), CD34+ collection efficiency was comparable between LVL and NVL (61.2% vs. 61.4%, p = .966). Platelet loss was significantly higher in LVL compared to NVL (38.0% vs. 29.4%, p < .001), with no correlation between attrition of platelet and processing blood volume. Moreover, the incidence of citrate toxicity during procedures was comparable between the two groups (31.6% vs. 21.4%, p = .322). All LVL procedures could be completed without any adverse events. CONCLUSION: Allogeneic LVL procedure using Spectra Optia cMNC protocol was well tolerated by the donors and resulted in efficient collection of CD34+ cells, which was comparable to that of NVL.

    DOI: 10.1111/trf.17563

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  • Distribution and clinical impact of molecular subtypes with Dark Zone signature of DLBCL in a Japanese real-world study. International journal

    Tomohiro Urata, Yusuke Naoi, Aixiang Jiang, Merrill Boyle, Kazutaka Sunami, Toshi Imai, Yuichiro Nawa, Yasushi Hiramatsu, Kazuhiko Yamamoto, Soichiro Fujii, Isao Yoshida, Tomofumi Yano, Ryota Chijimatsu, Hiroyuki Murakami, Kazuhiro Ikeuchi, Hiroki Kobayashi, Katsuma Tani, Hideki Ujiie, Hirofumi Inoue, Shuta Tomida, Akira Yamamoto, Takumi Kondo, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Keisuke Sawada, Shuji Momose, Jun-Ichi Tamaru, Asami Nishikori, Yasuharu Sato, Tadashi Yoshino, Yoshinobu Maeda, David W Scott, Daisuke Ennishi

    Blood advances   2023.8

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    The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone, that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, that include the dark zone signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a dataset from the cohort of BC Cancer (BCC) (n = 804). Of the 1050 patients where DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to be germinal center B-cell-like (GCB)-DLBCL, activated B-cell-like (ABC)-DLBCL, and DZsigpos-DLBCL, respectively, with the highest prevalence of ABC-DLBCL differing significantly from that of BCC (P < 0.001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with two-year overall survival rates of 88%, 75%, and 66%, respectively (P < 0.0001), with patients of the DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes following rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all P < 0.05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas.

    DOI: 10.1182/bloodadvances.2023010402

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  • Feasibility of Flow Cytometry Analysis of Gastrointestinal Tract-Residing Lymphocytes in Hematopoietic Stem Cell Transplant Recipients

    Masaya Iwamuro, Takumi Kondo, Daisuke Ennishi, Nobuharu Fujii, Ken-ichi Matsuoka, Takahide Takahashi, Araki Hirabata, Takehiro Tanaka, Fumio Otsuka, Yoshinobu Maeda, Hiroyuki Okada

    Acta Medica Okayama   2023.8

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    DOI: 10.18926/AMO/65740

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  • Cyclin D2-positive mantle cell lymphoma with t(2;12)(p12;p13) arising in immune deficiency/dysregulation

    Takumi Kondo, Mitsuko Iguchi, Shohei Yoshida, Tadashi Yoshino, Kensuke Kojima

    Annals of Hematology   2023.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media {LLC}  

    DOI: 10.1007/s00277-023-05330-2

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  • Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch

    Takumi Kondo, Keiko Fujii, Nobuharu Fujii, Yuichi Sumii, Tomohiro Urata, Maiko Kimura, Masayuki Matsuda, Shuntaro Ikegawa, Kana Washio, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken‐ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda

    Transfusion   2023.6

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    Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1111/trf.17450

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  • 臍帯血移植後にHTLV-1感染T細胞の多クローン性増殖を伴って発症した肺合併症に対し抗CCR4抗体が著効した1例

    松原 千哲, 松岡 賢市, 近藤 歌穂, 藤原 加奈子, 寺尾 俊紀, 植田 裕子, 松村 彰文, 守山 喬史, 村上 裕之, 近藤 匠, 清家 圭介, 藤原 英晃, 淺田 騰, 遠西 大輔, 西森 久和, 藤井 敬子, 藤井 伸治, 前田 嘉信

    臨床血液   64 ( 6 )   563 - 563   2023.6

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    Language:Japanese   Publisher:(一社)日本血液学会-東京事務局  

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  • 臍帯血移植後にHTLV-1感染T細胞の多クローン性増殖を伴って発症した肺合併症に対し抗CCR4抗体が著効した1例

    松原 千哲, 松岡 賢市, 近藤 歌穂, 藤原 加奈子, 寺尾 俊紀, 植田 裕子, 松村 彰文, 守山 喬史, 村上 裕之, 近藤 匠, 清家 圭介, 藤原 英晃, 淺田 騰, 遠西 大輔, 西森 久和, 藤井 敬子, 藤井 伸治, 前田 嘉信

    臨床血液   64 ( 6 )   563 - 563   2023.6

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    Language:Japanese   Publisher:(一社)日本血液学会-東京事務局  

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  • Hematopoietic stem cell–derived Tregs are essential for maintaining favorable B cell lymphopoiesis following posttransplant cyclophosphamide

    Yuichi Sumii, Takumi Kondo, Shuntaro Ikegawa, Takuya Fukumi, Miki Iwamoto, Midori Filiz Nishimura, Hiroyuki Sugiura, Yasuhisa Sando, Makoto Nakamura, Yusuke Meguri, Takashi Matsushita, Naoki Tanimine, Maiko Kimura, Noboru Asada, Daisuke Ennishi, Yoshinobu Maeda, Ken-ichi Matsuoka

    JCI Insight   8 ( 8 )   2023.4

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    Publishing type:Research paper (scientific journal)   Publisher:American Society for Clinical Investigation  

    DOI: 10.1172/jci.insight.162180

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  • Ferroportin diseaseにおける妊娠・出産時の鉄代謝管理

    慶斗 大原, 典子 津下, 伸一朗 渡部, 仁海 江田, 史也 小笠原, 匠 近藤, 将平 吉田, 研介 小島

    臨床血液   2023

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.11406/rinketsu.64.1410

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  • Early initiation of low-dose gilteritinib maintenance improves posttransplant outcomes in patients with R/R FLT3mut AML. International journal

    Toshiki Terao, Ken-Ichi Matsuoka, Hiroko Ueda, Akifumi Matsumura, Chisato Matsubara, Kaho Kondo, Takumi Kondo, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Yoshinobu Maeda

    Blood advances   7 ( 5 )   681 - 686   2022.12

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    DOI: 10.1182/bloodadvances.2022008991

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  • Red blood cell depletion in small‐volume bone marrow processing using manipulation with third‐party red blood cells: A comparison of the performance of the COBE spectra and the spectra Optia systems

    Yuichi Sumii, Nobuharu Fujii, Keiko Fujii, Takumi Kondo, Tomohiro Urata, Maiko Kimura, Kana Washio, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken‐ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda

    Transfusion   2022.8

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    Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1111/trf.17039

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/trf.17039

  • Responses of regulatory and effector T-cells to low-dose interleukin-2 differ depending on the immune environment after allogeneic stem cell transplantation

    Yusuke Meguri, Takeru Asano, Takanori Yoshioka, Miki Iwamoto, Shuntaro Ikegawa, Hiroyuki Sugiura, Yuriko Kishi, Makoto Nakamura, Yasuhisa Sando, Takumi Kondo, Yuichi Sumii, Yoshinobu Maeda, Ken-ichi Matsuoka

    Frontiers in Immunology   13   2022.8

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    Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media {SA}  

    <jats:p>CD4<jats:sup>+</jats:sup>Foxp3<jats:sup>+</jats:sup> regulatory T cells (Tregs) play a central role in the maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT). Tregs promptly respond to low concentrations of IL-2 through the constitutive expression of high-affinity IL-2 receptors. It has been reported that low-dose IL-2 therapy increased circulating Tregs and improved clinical symptoms of chronic GVHD. Clinical studies of IL-2 therapy so far have mainly targeted patients in the chronic phase of transplantation when acute immune responses has subsided. However, the biological and clinical effects of exogenous IL-2 in an acute immune environment have not been well investigated. In the current study, we investigated the impact of exogenous IL-2 therapy on the post-transplant homeostasis of T cell subsets which influence the balance between GVHD and GVL in the acute phase, by setting the various immune environments early after HSCT in murine model. We initially found that 5,000 IU of IL-2 was enough to induce the active proliferation of Treg without influencing other conventional T cells (Tcons) when administered to normal mice. However, activated Tcons showed the response to the same dose of IL-2 in recipients after allogeneic HSCT. In a mild inflammatory environment within a threshold, exogenous IL-2 could effectively modulate Treg homeostasis with just limited influence to activated T cells, which resulted in an efficient GVHD suppression. In contrast, in a severely inflammatory environment, exogenous IL-2 enhanced activated T cells rather than Tregs, which resulted in the exacerbation of GVHD. Of interest, in an immune-tolerant state after transplant, exogenous IL-2 triggered effector T-cells to exert an anti-tumor effect with maintaining GVHD suppression. These data suggested that the responses of Tregs and effector T cells to exogenous IL-2 differ depending on the immune environment in the host, and the mutual balance of the response to IL-2 between T-cell subsets modulates GVHD and GVL after HSCT. Our findings may provide useful information in the optimization of IL-2 therapy, which may be personalized for each patient having different immune status.</jats:p>

    DOI: 10.3389/fimmu.2022.891925

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  • Low hematocrit reduces the efficiency of CD34 + cell collection when using the Spectra Optia continuous mononuclear cell collection procedure

    Takumi Kondo, Nobuharu Fujii, Keiko Fujii, Yuichi Sumii, Tomohiro Urata, Maiko Kimura, Masayuki Matsuda, Shuntaro Ikegawa, Kana Washio, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken‐ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda

    Transfusion   62 ( 5 )   1065 - 1072   2022.5

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    DOI: 10.1111/trf.16856

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  • Successful neutrophil engraftment supported by granulocyte transfusion in adult allogeneic transplant patients with peri-transplant active infection International journal

    Shuntaro Ikegawa, Nobuharu Fujii, Keiko Fujii, Maiko Kimura, Masayuki Matsuda, Takumi Kondo, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-ichi Matsuoka, Yoshinobu Maeda

    Transfusion and Apheresis Science   61 ( 6 )   103453 - 103453   2022.5

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    Active infection at the time of allogeneic hematopoietic stem cell transplantation (HSCT) is a risk for non-relapse mortality (NRM) after HSCT. Granulocyte transfusion (GTX) has been used to prevent or treat life-threatening infections in patients with severe neutropenia. However, data are limited on the clinical benefits of GTX during HSCT. We retrospectively analyzed the transplant outcomes of HSCT patients who had undergone GTX between 2012 and 2020. Altogether, 20 patients with documented infection had received 55 GTXs during HSCT. No adverse events were observed during the GTX infusion. The average number of granulocytes was 0.40 (range, 0.10-1.59) × 109/kg. The median neutrophil increment one day after GTX was 515 (range, -6 to 6630)/μl, which was significantly correlated with the infused granulocyte dose (p = 0.0007). A total of 17 of 20 patients achieved neutrophil engraftment. The number of infused granulocytes tended to higher in clinical responders (p = 0.12), and patients receiving ≥ 0.5 × 109/kg showed trend toward to better transplant outcomes (GTX-high vs. GTX-low, 1-year OS; 33% vs. 11%, p = 0.19. 1-year NRM; 44% vs.77%, p = 0.11). The type of red blood sedimenting agents was significantly correlated with the amounts of granulocyte collection. In conclusion, GTX, especially with a high amount of containing granulocytes, could be a safe bridging therapy for neutrophil engraftment after HSCT in patients with active infection.

    DOI: 10.1016/j.transci.2022.103453

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  • Author Correction: 5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy (Scientific Reports, (2020), 10, 1, (17237), 10.1038/s41598-020-74174-x)

    Yasuhisa Sando, Ken-ichi Matsuoka, Yuichi Sumii, Takumi Kondo, Shuntaro Ikegawa, Hiroyuki Sugiura, Makoto Nakamura, Miki Iwamoto, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Atae Utsunomiya, Takashi Oka, Yoshinobu Maeda

    Scientific Reports   11 ( 1 )   2021.12

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    The Supplementary Information published with this Article contains errors. The degree of Takashi Oka, “PhD., DMSc”, is incorrectly given as “PhD”. In addition, the excitation wavelength measurements within the “Supplemental materials and methods” section is omitted. Lastly, the explanation of the Figures given in the legend of Figures S4 and S5 is incorrect. The correct Supplementary Information file is linked to this correction notice.

    DOI: 10.1038/s41598-021-86066-9

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  • Reduced dose of PTCy followed by adjuvant α-galactosylceramide enhances GVL effect without sacrificing GVHD suppression International journal

    Makoto Nakamura, Yusuke Meguri, Shuntaro Ikegawa, Takumi Kondo, Yuichi Sumii, Takuya Fukumi, Miki Iwamoto, Yasuhisa S, o, Hiroyuki Sugiura, Noboru Asada, Daisuke Ennishi, Shuta Tomida, Emi Fukuda-Kawaguchi, Yasuyuki Ishii, Yoshinobu Maeda, Ken-ichi Matsuoka

    Scientific Reports   11 ( 1 )   13125 - 13125   2021.12

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    <jats:title>Abstract</jats:title><jats:p>Posttransplantation cyclophosphamide (PTCy) has become a popular option for haploidentical hematopoietic stem cell transplantation (HSCT). However, personalized methods to adjust immune intensity after PTCy for each patient’s condition have not been well studied. Here, we investigated the effects of reducing the dose of PTCy followed by α-galactosylceramide (α-GC), a ligand of iNKT cells, on the reciprocal balance between graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect. In a murine haploidentical HSCT model, insufficient GVHD prevention after reduced-dose PTCy was efficiently compensated for by multiple administrations of α-GC. The ligand treatment maintained the enhanced GVL effect after reduced-dose PTCy. Phenotypic analyses revealed that donor-derived B cells presented the ligand and induced preferential skewing to the NKT2 phenotype rather than the NKT1 phenotype, which was followed by the early recovery of all T cell subsets, especially CD4<jats:sup>+</jats:sup>Foxp3<jats:sup>+</jats:sup> regulatory T cells. These studies indicate that α-GC administration soon after reduced-dose PTCy restores GVHD-preventing activity and maintains the GVL effect, which is enhanced by reducing the dose of PTCy. Our results provide important information for the development of a novel strategy to optimize PTCy-based transplantation, particularly in patients with a potential relapse risk.</jats:p>

    DOI: 10.1038/s41598-021-92526-z

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  • Donor Treg expansion by liposomal α‐galactosylceramide modulates Tfh cells and prevents sclerodermatous chronic graft‐versus‐host disease International journal

    Hiroyuki Sugiura, Ken-ichi Matsuoka, Takuya Fukumi, Yuichi Sumii, Takumi Kondo, Shuntaro Ikegawa, Yusuke Meguri, Miki Iwamoto, Yasuhisa S, o, Makoto Nakamura, Tomohiro Toji, Yasuyuki Ishii, Yoshinobu Maeda

    Immunity, Inflammation and Disease   9 ( 3 )   721 - 733   2021.9

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    BACKGROUND AND AIM: Chronic graft-versus-host disease (cGVHD) is a major cause of nonrelapse morbidity and mortality following hematopoietic stem cell transplantation (HSCT). α-Galactosylceramide (α-GC) is a synthetic glycolipid that is recognized by the invariant T-cell receptor of invariant natural killer T (iNKT) cells in a CD1d-restricted manner. Stimulation of iNKT cells by α-GC leads to the production of not only immune-stimulatory cytokines but also immune-regulatory cytokines followed by regulatory T-cell (Treg) expansion in vivo. METHODS: We investigated the effect of iNKT stimulation by liposomal α-GC just after transplant on the subsequent immune reconstitution and the development of sclerodermatous cGVHD. RESULTS: Our study showed that multiple administrations of liposomal α-GC modulated both host- and donor-derived iNKT cell homeostasis and induced an early expansion of donor Tregs. We also demonstrated that the immune modulation of the acute phase was followed by the decreased levels of CXCL13 in plasma and follicular helper T cells in lymph nodes, which inhibited germinal center formation, resulting in the efficient prevention of sclerodermatous cGVHD. CONCLUSIONS: These data demonstrated an important coordination of T- and B-cell immunity in the pathogenesis of cGVHD and may provide a novel clinical strategy for the induction of immune tolerance after allogeneic HSCT.

    DOI: 10.1002/iid3.425

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  • Effectiveness of supplemental oral calcium drink in preventing citrate-related adverse effects in peripheral blood progenitor cell collection International journal

    Keiko Fujii, Nobuharu Fujii, Takumi Kondo, Toshiharu Mitsuhashi, Makoto Nakamura, Keisuke Seike, Yasuhisa S, o, Maiko Kimura, Masayuki Matsuda, Shuntaro Ikegawa, Hiroyuki Sugiura, Fumio Otsuka, Yoshinobu Maeda

    Transfusion and Apheresis Science   60 ( 4 )   103147 - 103147   2021.8

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    Peripheral blood progenitor cells (PBPCs) are a predominant graft source in allogeneic hematopoietic cell transplantation. Citrate-induced hypocalcemia remains the most frequent side effect of PBPC apheresis. Although the method for preventing severe adverse events is established, more efficient prophylaxis is required so that volunteer donors can donate PBPCs without pain and anxiety. We studied 80 healthy donors who underwent PBPC harvest between February 2014 and June 2020. Of these, 23 donors who underwent apheresis between February 2014 and December 2015 received only the standard prophylaxis of intravenous calcium gluconate. Oral calcium drinks were provided to 57 donors who underwent apheresis from January 2016 to June 2020 to supplement intravenous calcium gluconate prophylaxis. The ionized calcium (ICa) levels at multiple time intervals and the hypocalcemic symptoms were evaluated. Oral supplementation with a calcium drink maintained significantly higher ICa levels. Analysis using the inverse probability weighted regression adjustment method suggested that calcium drinks reduced the frequency of citrate-related reactions by 39.2 %. Administering a prophylactic oral calcium drink before apheresis with intravenous administration of calcium gluconate is promising to further reduce citrate-induced hypocalcemia in volunteer donors.

    DOI: 10.1016/j.transci.2021.103147

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  • Pretransplant Short-Term Exposure of Donor Graft Cells to ITK Selective Inhibitor Ameliorates Acute Graft-versus-Host Disease by Inhibiting Effector T Cell Differentiation while Sparing Regulatory T Cells International journal

    Takumi Kondo, Shuntaro Ikegawa, Takuya Fukumi, Yuichi Sumii, Hiroyuki Sugiura, Yasuhisa S, o, Makoto Nakamura, Yusuke Meguri, Miki Iwamoto, Yoshinobu Maeda, Ken-ichi Matsuoka

    ImmunoHorizons   5 ( 6 )   424 - 437   2021.6

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    Graft-versus-host disease (GVHD) remains to be a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). IL-2-inducible T cell kinase (ITK), a TEC cytoplasmic tyrosine kinase, has an essential role in T cell development and receptor signaling. The ITK/Bruton tyrosine kinase inhibitor ibrutinib has been shown to improve chronic GVHD symptoms; however, the effect of ITK selective inhibition on acute GVHD remains unclear. In this study, we evaluated the pharmacological effects of an ITK selective inhibitor (ITKsi) on acute GVHD using murine bone marrow transplantation models. First, we found that CD4+ T cell differentiation toward Th1, Th2, or Th17 was inhibited following ITKsi treatment in a dose-dependent manner while maintaining regulatory T cells in the presence of alloantigens both in vitro and in vivo. ITKsi preferentially inhibited inflammatory cytokine production and in vivo proliferation of alloreactive T cells. We then demonstrated that short-term exposure of donor graft cells to ITKsi significantly delayed the onset of GVHD-associated mortality without compromising the donor cell engraftment and the graft-versus-tumor effect, indicating the potential of ITK selective inhibition in the setting of clinical allogeneic HSCT. These findings suggest that ITK is a potential therapeutic target against GVHD, and the pharmacological ITK inhibitor may serve as a novel strategy for immune regulation after HSCT.

    DOI: 10.4049/immunohorizons.2100042

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  • 移植後シクロホスファミドを用いた血縁者間HLA半合致移植後に最重症遅発性肝類洞閉塞症候群を合併した非定型慢性骨髄性白血病

    北村 亘, 藤井 伸治, 大西 秀樹, 高須賀 裕樹, 大山 矩史, 村上 裕之, 木村 真衣子, 近藤 匠, 松田 真幸, 池川 俊太郎, 藤原 英晃, 淺田 騰, 遠西 大輔, 西森 久和, 藤井 敬子, 松岡 賢市, 木口 亨, 柳井 広之, 吉野 正, 前田 嘉信

    臨床血液   62 ( 6 )   654 - 655   2021.6

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  • 骨髄濃縮を行った骨髄移植72症例の後方視的検討 赤血球除去の有効性、骨髄凍結の安全性を含めて

    藤井 敬子, 木村 真衣子, 近藤 匠, 松田 真幸, 高橋 孝英, 高木 尚江, 閘 結稀, 池田 亮, 浅野 尚美, 小郷 博昭, 前田 嘉信, 大塚 文男, 藤井 伸治

    日本輸血細胞治療学会誌   67 ( 2 )   325 - 325   2021.5

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  • Post-transplantation cyclophosphamide restores early B-cell lymphogenesis that suppresses subsequent chronic graft-versus-host disease

    Miki Iwamoto, Shuntaro Ikegawa, Takumi Kondo, Yusuke Meguri, Makoto Nakamura, Yasuhisa S, o, Hiroyuki Sugiura, Yuichi Sumii, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Misako Shibakura, Yoshinobu Maeda, Ken-ichi Matsuoka

    Bone Marrow Transplantation   56 ( 4 )   956 - 959   2021.4

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    DOI: 10.1038/s41409-020-01100-0

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  • Pretransplant nivolumab further enhanced Treg expansion after posttransplant cyclophosphamide; another aspect for immune tolerance by PTCy after nivolumab

    Shuntaro Ikegawa, Yusuke Meguri, Kentaro Mizuhara, Takuya Fukumi, Hiroki Kobayashi, Yuichi Sumii, Takumi Kondo, Yasuhisa S, o, Miki Iwamoto, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Yuka Fujisawa, Toshi Imai, Yoshinobu Maeda, Ken-ichi Matsuoka

    Leukemia   35 ( 3 )   929 - 931   2021.3

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    DOI: 10.1038/s41375-021-01167-8

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  • 5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy

    Yasuhisa S, o, Ken-ichi Matsuoka, Yuichi Sumii, Takumi Kondo, Shuntaro Ikegawa, Hiroyuki Sugiura, Makoto Nakamura, Miki Iwamoto, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Atae Utsunomiya, Takashi Oka, Yoshinobu Maeda

    Scientific Reports   10 ( 1 )   2020.12

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    <jats:title>Abstract</jats:title><jats:p>Photodynamic therapy (PDT) is an emerging treatment for various solid cancers. We recently reported that tumor cell lines and patient specimens from adult T cell leukemia/lymphoma (ATL) are susceptible to specific cell death by visible light exposure after a short-term culture with 5-aminolevulinic acid, indicating that extracorporeal photopheresis could eradicate hematological tumor cells circulating in peripheral blood. As a bridge from basic research to clinical trial of PDT for hematological malignancies, we here examined the efficacy of ALA-PDT on various lymphoid malignancies with circulating tumor cells in peripheral blood. We also examined the effects of ALA-PDT on tumor cells before and after conventional chemotherapy. With 16 primary blood samples from 13 patients, we demonstrated that PDT efficiently killed tumor cells without influencing normal lymphocytes in aggressive diseases such as acute ATL. Importantly, PDT could eradicate acute ATL cells remaining after standard chemotherapy or anti-CCR4 antibody, suggesting that PDT could work together with other conventional therapies in a complementary manner. The responses of PDT on indolent tumor cells were various but were clearly depending on accumulation of protoporphyrin IX, which indicates the possibility of biomarker-guided application of PDT. These findings provide important information for developing novel therapeutic strategy for hematological malignancies.</jats:p>

    DOI: 10.1038/s41598-020-74174-x

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  • PTCy ameliorates GVHD by restoring regulatory and effector T-cell homeostasis in recipients with PD-1 blockade International journal

    Shuntaro Ikegawa, Yusuke Meguri, Takumi Kondo, Hiroyuki Sugiura, Yasuhisa S, o, Makoto Nakamura, Miki Iwamoto, Yoshinobu Maeda, Ken-ichi Matsuoka

    Blood Advances   3 ( 23 )   4081 - 4094   2019.12

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    <jats:title>Key Points</jats:title>
    <jats:p>PD-1 blockade exacerbated GVHD by altering the homeostasis of Tregs and effector T cells after HSCT. PTCy ameliorated GVHD after PD-1 blockade by restoring the homeostatic balance of T-cell subsets.</jats:p>

    DOI: 10.1182/bloodadvances.2019000134

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  • Salvage Haploidentical Transplantation Using Low-dose ATG for Early Disease Relapse after First Allogeneic Transplantation: A Retrospective Single-center Review

    Takumi KONDO

    Acta Medica Okayama   2019.4

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    DOI: 10.18926/AMO/56652

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  • Papuloerythroderma-like cutaneous involvement of a CD62L−subclone of T-cell prolymphocytic leukemia

    Yuki Nakagawa, Toshihisa Hamada, Mayuko Matsuda, Taisuke Kanno, Takumi Kondo, Takahide Takahashi, Toshiyuki Watanabe, Ken Okada, Toru Kawakami, Tomoko Miyake, Shin Morizane, Keiji Iwatsuki

    The Journal of Dermatology   46 ( 1 )   65 - 69   2019.1

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    DOI: 10.1111/1346-8138.14702

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  • Dynamic Shifts in Inflammation and Fibrotic Remodeling in Post-HSCT Bronchiolitis Obliterans: A Spatial Transcriptomics Study

    Akira Yamamoto, Nobuharu Fujii, Keisuke Seike, Seiichiro Sugimoto, Yusuke Naoi, Yui Kambara, Kanako Fujiwara, Toshiki Terao, Tadashi Oyama, Mari Kunihiro, Takumi Kondo, Hiroki Kobayashi, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Shinichi Toyooka, Yoshinobu Maeda

    Blood   2024.11

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    <jats:sec>
    <jats:title/>
    <jats:p>Bronchiolitis obliterans (BO) is a severe complication following hematopoietic stem cell transplantation (HSCT), significantly impacting patients' prognosis and quality of life. Despite its clinical importance, the underlying pathophysiological mechanisms remain poorly understood.</jats:p>
    <jats:p>We analyzed lung specimens from three patients who developed BO post-HSCT and subsequently underwent lung transplantation. All patients had acute lymphoblastic leukemia as their primary disease and developed BO 1-2 years after HSCT. Healthy lung regions from two cancer patients served as controls. Using NanoString GeoMx Digital Spatial Profiling, we performed transcriptional profiling with the Human Whole Transcriptome Atlas on 94 regions of interest (ROIs). BO lesions were classified based on our previously established staging system (Kuroi T et al. Int J Hematol. 2021) and analyzed for both inner and outer bronchiolar regions.</jats:p>
    <jats:p>Linear mixed model analysis identified significant differential gene expression between BO and control groups. GO enrichment analysis highlighted biological processes such as phagocytosis, positive regulation of leukocyte activation, and cell activation, indicating a close association with immune cells, particularly macrophages, which are known to obstruct bronchioles in BO. Processes such as regulation of cell-cell adhesion and post-Golgi vesicle-mediated transport were also enriched, suggesting involvement in extracellular matrix remodeling and fibroblast activation. GSEA further identified significant processes, including inflammatory response, defense response, positive regulation of response to stimulus, and vesicle-mediated transport. These results suggest an interplay between immune response and tissue remodeling. Notably, changes in the expression of genes such as HES1, IGF2BP2, PTPRF, and ITGB2, which are involved in cell adhesion and cytoskeletal reorganization, were closely associated with fibroblast activation and macrophage infiltration. These findings parallel the fibrosis process observed in BO following lung transplantation, where macrophage infiltration and myofibroblast activation are critical. Given these insights, our focus shifted to the dynamics of macrophages and myofibroblasts, aiming to understand their roles in the progression from inflammation to tissue remodeling.</jats:p>
    <jats:p>CD68, a pan-macrophage marker, showed higher expression in Early and Middle-outside stages (Inflammatory Phase) of BO, but significantly decreased in Middle-inside and Late stages (Remodeling Phase) as the disease progressed. Unsupervised clustering analysis revealed distinct gene expression profiles between these phases, suggesting a temporal shift in disease mechanisms as BO progresses from inner bronchioles outwards. Correlation analysis revealed significant associations between CD68 and JAK1/STAT1 expression, as well as genes associated with myofibroblast activity and extracellular matrix remodeling (e.g., ACTA2, TGFB1). These findings suggest a coordinated process of inflammation and remodeling in BO, potentially involving the JAK-STAT pathway.</jats:p>
    <jats:p>Linear mixed model analysis revealed distinct gene expression patterns between Inflammatory and Remodeling Phases, characterized by inflammatory/proliferation-related genes (e.g., CXCL6, HLA-family) and tissue remodeling/protein synthesis and genes (e.g., ITGB1, RPL and RPS families), respectively. This transition aligns with changes in macrophage-related gene expression. Pathway analysis revealed enrichment of translation, ribosomal activity, and metabolic processes in the Remodeling Phase, indicating a dynamic shift in biological activities as BO progresses.</jats:p>
    <jats:p>In conclusion, this study reveals a transition in BO pathology from inflammation to remodeling, with macrophages playing a central role. The coordinated changes in gene expression provide a comprehensive picture of BO progression. These insights into post-HSCT BO pathophysiology highlight potential therapeutic targets in macrophage function and tissue remodeling pathways, suggesting possibilities for stage-specific interventions in BO treatment.</jats:p>
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    DOI: 10.1182/blood-2024-202251

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  • ベネトクラクス,アザシチジンを含む化学療法後に初回同種造血幹移植を施行した急性骨髄性白血病の治療成績

    松原 千哲, 藤原 英晃, 林野 健太, 近藤 歌穂, 藤原 加奈子, 寺尾 俊紀, 植田 裕子, 松村 彰文, 大山 矩史, 鴨井 千尋, 村上 裕之, 守山 喬史, 近藤 匠, 清家 圭介, 淺田 騰, 遠西 大輔, 西森 久和, 藤井 敬子, 藤井 伸治, 松岡 賢市, 前田 嘉信

    日本血液学会学術集会   85回   1250 - 1250   2023.10

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  • 臍帯血移植後にHTLV-1感染T細胞の多クローン性増殖を伴って発症した肺合併症に対しCCR4抗体が著効した一例

    松原千哲, 松岡賢市, 近藤歌穂, 藤原加奈子, 寺尾俊紀, 植田裕子, 松村彰文, 守山喬史, 村上裕之, 近藤匠, 清家圭介, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 藤井敬子, 藤井伸治, 中島誠, 中島誠, 内丸薫, 前田嘉信

    日本血液学会学術集会抄録(Web)   85th   2023

  • Gilteritinib maintenance therapy post-SCT improves the prognosis of patients with R/R FLT3mut AML

    寺尾俊紀, 松岡賢市, 植田裕子, 松村彰文, 松原千哲, 近藤歌穂, 近藤匠, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 藤井敬子, 藤井伸治, 前田嘉信

    日本造血・免疫細胞療法学会総会プログラム・抄録集   45th   2022

  • Open-label, randomized study to calcium drink for prevention of citrate toxicity of PBSC donor

    藤井敬子, 藤井敬子, 藤井伸治, 藤井伸治, 三橋利晴, 住居優一, 住居優一, 谷勝真, 谷勝真, 浦田知宏, 浦田知宏, 木村真衣子, 木村真衣子, 近藤匠, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 松岡賢市, 大塚文男, 前田嘉信

    日本造血・免疫細胞療法学会総会プログラム・抄録集   45th   2022

  • Influence of oral microbiota on graft-versus-host disease and its role as a therapeutic target

    神原由依, 藤原英晃, 山本晃, 國廣まり, 大山矩史, 近藤匠, 淺田騰, 遠西大輔, 西森久和, 藤井伸治, 藤井敬子, 松岡賢市, 前田嘉信, 前田嘉信

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