Updated on 2025/04/05

写真a

 
Seike Keisuke
 
Organization
Scheduled update Assistant Professor
Position
Assistant Professor
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Degree

  • Doctor of Philosophy in Medical Science ( 2020.6   Okayama University, Graduate School of Medicine, Density and Pharmaceutical Medicine )

  • Doctor of Medicine ( 2011.3   Okayama University )

Research Interests

  • Hematopoietic stem cell transplant

  • GVHD

  • microbiome

  • T cells

Research Areas

  • Life Science / Hematology and medical oncology

Education

  • Okayama University   大学院医歯薬学総合研究科  

    2016.4 - 2020.6

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    Country: Japan

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  • Okayama University   医学部   医学科

    2005.4 - 2011.3

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    Country: Japan

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  • 愛媛県立松山東高等学校    

    2000.4 - 2003.3

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Research History

  • 岡山大学病院   助教

    2023.4

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

    2022.10 - 2023.3

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    Country:Japan

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  • University of Michigan   Department of Internal Medicine, Division of Hematology/Oncology   Postdoctoral research fellow

    2020.1 - 2022.9

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    Country:United States

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  • Okayama University Hospital   輸血部

    2017.6 - 2019.12

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    Country:Japan

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  • Okayama University Hospital   血液・腫瘍内科

    2014.9 - 2016.3

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    Country:Japan

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  • 亀田総合病院

    2013.9 - 2014.8

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    Country:Japan

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  • 岡山市立市民病院

    2011.4 - 2013.8

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    Country:Japan

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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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    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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    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 Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease. International journal

    Yui Kambara, Hideaki Fujiwara, Akira Yamamoto, Kazuyoshi Gotoh, Shuma Tsuji, Mari Kunihiro, Tadashi Oyama, Toshiki Terao, Ayame Sato, Takehiro Tanaka, Daniel Peltier, Keisuke Seike, Hisakazu Nishimori, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshihiko Soga, Pavan Reddy, Yoshinobu Maeda

    Blood   2024.12

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    The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in GVHD pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients post-hematopoietic cell transplantation associated with increased chronic GVHD (cGVHD) even in patients receiving post-transplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes (LNs) both pre- and post-transplantation activated antigen-presenting cells (APCs), thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increased in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD.

    DOI: 10.1182/blood.2024024540

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  • Outcomes of allogeneic SCT versus tisagenlecleucel in patients with R/R LBCL and poor prognostic factors.

    Kenta Hayashino, Toshiki Terao, Hisakazu Nishimori, Wataru Kitamura, Hiroki Kobayashi, Chihiro Kamoi, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

    International journal of hematology   2024.12

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    This study investigated the efficacy of tisagenlecleucel (tisa-cel) and allogeneic hematopoietic stem cell transplantation (allo-SCT) for patients with relapsed and/or refractory (r/r) large B-cell lymphoma (LBCL) with poor prognostic factors, defined as performance status (PS) ≥ 2, multiple extranodal lesions (EN), chemorefractory disease, or higher lactate dehydrogenase (LDH). Overall, the allo-SCT group demonstrated worse progression-free survival (PFS), higher non-relapse mortality, and a similar relapse/progression rate. Notably, the tisa-cel group showed better PFS than the allo-SCT group among patients with chemorefractory disease (3.2 vs. 2.0 months, p = 0.092) or higher LDH (4.0 vs. 2.0 months, p = 0.018), whereas PFS in the two cellular therapy groups was similar among those with PS ≥ 2 or multiple EN. Survival time after relapse post-cellular therapy in patients with poor prognostic factors was 1.6 with allo-SCT and 4.6 months with tisa-cel. These findings were confirmed in a propensity score matching cohort. In conclusion, tisa-cel resulted in better survival than allo-SCT in patients with poor prognostic factors. However, patients who relapsed post-cellular therapy had dismal outcomes regardless of therapy. Further strategies are warranted to improve outcomes in these patients.

    DOI: 10.1007/s12185-024-03888-9

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  • 中枢神経原発リンパ腫におけるplasmablastサブポピュレーションの分子学的特性について

    小林 宏紀, 千々松 良太, 直井 友亮, 大谷 理浩, 水田 亮, 藤井 謙太郎, 石田 穣治, 村上 裕之, 氏家 英貴, 池内 一廣, 浦田 知宏, 清家 圭介, 藤原 英晃, 淺田 騰, 藤井 伸治, 松岡 賢市, 佐藤 康晴, 前田 嘉信, 遠西 大輔

    日本血液学会学術集会   86回   O3 - 2   2024.10

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  • Simulation-based Bone Marrow Aspiration and Trephine Biopsy Education for Medical Students: A Non-randomized Controlled Trial. Reviewed

    Akira Yamamoto, Hisakazu Nishimori, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

    Internal medicine (Tokyo, Japan)   2024.7

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    Introduction Despite the critical role of bone marrow aspiration and a trephine biopsy (BMAT) in the diagnosis and management of hematological diseases, research on effective teaching methods is limited. Medical students traditionally learn to perform BMAT through observation and replication, which poses a risk to patient safety. Therefore, we developed a novel BMAT simulator for undergraduate medical students using a simulation-based education program. Methods This program, designed for fourth- and fifth-year medical students at Okayama University Medical School, included pre-study materials and one hour of simulation training. Internists practicing hematology served as the controls. Before and after the simulation training, the students completed questionnaires regarding self-confidence, self-evaluation, interest, and knowledge. The procedures were evaluated objectively using a checklist at the end of the program. Results There were significant improvements in self-evaluation, self-confidence, interest, and knowledge acquisition after the simulation program (p≤0.001). The checklist revealed that the mean overall proficiency level of the students was 76.9%, which was significantly higher than that of internists (63.5%) (p≤0.01). Conclusion Our simulation-based education program using the novel BMAT simulator improved medical students' BMAT knowledge and skills.

    DOI: 10.2169/internalmedicine.3998-24

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  • HAVCR2ホモ接合型変異を有し家族内発症した皮下脂肪織炎様T細胞リンパ腫

    植田 裕子, 藤井 伸治, 松原 千哲, 近藤 歌穂, 寺尾 俊紀, 松村 彰文, 清家 圭介, 藤原 英晃, 淺田 騰, 遠西 大輔, 藤井 敬子, 松岡 賢市, 森坂 広行, 綾田 善行, 吉野 正, 前田 嘉信

    臨床血液   65 ( 5 )   465 - 466   2024.5

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

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  • 造血幹細胞移植後の難治性腸管合併症に対して腸管切除術を施行した2症例

    田中 謙太郎, 山本 晃, 藤井 伸治, 近藤 喜太, 田中 健大, 清家 圭介, 藤原 英晃, 淺田 騰, 遠西 大輔, 藤井 敬子, 松岡 賢市, 松川 昭博, 吉野 正, 前田 嘉信

    臨床血液   65 ( 5 )   454 - 454   2024.5

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  • Sigle Agent of Posttransplant Cyclophosphamide Without Calcineurin Inhibitor Controls Severity of Experimental Chronic GVHD. Reviewed

    Kyosuke Saeki, Hideaki Fujiwara, Keisuke Seike, Taiga Kuroi, Hisakazu Nishimori, Takehiro Tanaka, Ken-Ichi Matsuoka, Nobuharu Fujii, Yoshinobu Maeda

    Acta medica Okayama   78 ( 2 )   123 - 134   2024.4

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    Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HCT), but its pathogenesis remains unclear. Recently, haplo-identical HCT with post-transplant cyclophosphamide (Haplo-HCT with PTCY) was found to achieve a low incidence rate of acute GVHD and chronic GVHD. However, while the pathogenesis of acute GVHD following Haplo-HCT with PTCY has been well investigated, that of chronic GVHD remains to be elucidated, especially in HLA-matched HCT with PTCY. Based on its safety profile, PTCY is currently applied for the human leucocyte antigen (HLA)-matched HCT setting. Here, we investigated the mechanisms of chronic GVHD following HLA-matched HCT with PTCY using a well-defined mouse chronic GVHD model. PTCY attenuated clinical and pathological chronic GVHD by suppressing effector T-cells and preserving regulatory T-cells compared with a control group. Additionally, we demonstrated that cyclosporine A (CsA) did not show any additional positive effects on attenuation of GVHD in PTCY-treated recipients. These results suggest that monotherapy with PTCY without CsA could be a promising strategy for the prevention of chronic GVHD following HLA-matched HCT.

    DOI: 10.18926/AMO/66915

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  • Chimeric antigen receptor T-cell therapy after COVID-19 in refractory high-grade B-cell lymphoma Reviewed

    Kenta Hayashino, Keisuke Seike, Kanako Fujiwara, Kaho Kondo, Chisato Matsubara, Toshiki Terao, Wataru Kitamura, Chihiro Kamoi, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-ichi Matsuoka, Yoshinobu Maeda

    International Journal of Hematology   2024.4

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s12185-024-03711-5

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  • Collection efficiency and safety of large-volume leukapheresis for the manufacturing of tisagenlecleucel. Reviewed International journal

    Wataru Kitamura, Tomohiro Urata, Keiko Fujii, Takuya Fukumi, Kazuhiro Ikeuchi, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Ken-Ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda, Nobuharu Fujii

    Transfusion   2024.2

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    BACKGROUND: In patients with relapsed or refractory B cell acute lymphoblastic leukemia or B cell non-Hodgkin lymphoma (r/r B-ALL/B-NHL) with low CD3+ cells in the peripheral blood (PB), sufficient CD3+ cell yield in a single day may not be obtained with normal-volume leukapheresis (NVL). Large-volume leukapheresis (LVL) refers to the processing of more than three times the total blood volume (TBV) in a single session for PB apheresis; however, the efficiency and safety of LVL for manufacturing of tisagenlecleucel (tisa-cel) remain unclear. This study aimed to investigate the tolerability of LVL. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (≥3-fold TBV) and NVL (<3-fold TBV) performed for patients with r/r B-ALL/B-NHL in our institution during November 2019 and September 2023. All procedures were performed using a continuous mononuclear cell collection (cMNC) protocol with the Spectra Optia. RESULTS: Although pre-apheresis CD3+ cells in the PB were significantly lower in LVL procedures (900 vs. 348/μL, p < .01), all patients could obtain sufficient CD3+ cell yield in a single day with a comparably successful rate of final products (including out-of-specification) between the two groups (97.2% vs. 100.0%, p = 1.00). The incidence and severity of citrate toxicity (no patients with grade ≥ 3) during procedures was not significantly different between the two groups (22.2% vs. 26.1%, p = .43) and no patient discontinued leukapheresis due to any complications. CONCLUSION: LVL procedures using Spectra Optia cMNC protocol was well tolerated and did not affect the manufacturing of tisa-cel.

    DOI: 10.1111/trf.17765

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  • Clinical significance of gynecological examinations in long-term follow-ups Reviewed

    Chihiro Kamoi, Nobuharu Fujii, Hirofumi Matsuoka, Kanayo Takahashi, Akira Yamamoto, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

    Japanese Journal of Transplantation and Cellular Therapy   13 ( 2 )   74 - 80   2024

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    Publishing type:Research paper (scientific journal)   Publisher:The Japan Society for Hematopoietic Stem Cell Transplantation  

    DOI: 10.7889/tct-23-015

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  • [Relapsed primary central nervous system lymphoma treated with CD19 chimeric antigen receptor T-cell therapy and allogeneic hematopoietic stem cell transplantation]. Reviewed

    Fuminari Fujii, Toshiki Terao, Hisakazu Nishimori, Kentaro Fujii, Toshihiko Matsuo, Tadashi Yoshino, Hiroko Ueda, Tadashi Oyama, Akifumi Matsumura, Kaho Kondo, Chisato Matsubara, Kanako Fujiwara, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

    [Rinsho ketsueki] The Japanese journal of clinical hematology   65 ( 7 )   622 - 627   2024

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    Relapsed and/or refractory (R/R) primary central nervous system lymphoma (PCNSL) has a poor prognosis. A 57-year-old man diagnosed with PCNSL achieved a complete response by high-dose methotrexate-based chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT). The disease was not cured, so he was treated with the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel after the third relapse. However, the disease relapsed again 28 days after CAR T-cell therapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was attempted as curative therapy after bridging with second ASCT and tirabrutinib monotherapy. Although a temporary response was achieved, the disease relapsed 98 days after allo-HSCT. While receiving tirabrutinib for relapse after allo-HSCT, the patient developed acute respiratory failure due to transplant-related toxicity and post-transplant thrombotic microangiopathy. He died 175 days after allo-HSCT. Although various treatments for PCNSL have been investigated in recent years, the treatment strategy for R/R PCNSL has not been established. Further studies are warranted to improve the outcomes of patients with R/R PCNSL.

    DOI: 10.11406/rinketsu.65.622

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  • T-cell mediated tissue injuries and the role of ETC functions in intestinal epithelial cells.

    藤原英晃, 清家圭介

    月刊臨床免疫・アレルギー科   80 ( 5 )   551 - 556   2023.11

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  • 高用量もしくは長期間のステロイド治療はtisagenlecleucelの効果を減弱させる

    寺尾 俊紀, 北村 亘, 藤井 伸治, 鴨井 千尋, 藤原 加奈子, 近藤 歌穂, 松原 千哲, 林野 健太, 清家 圭介, 藤原 英晃, 淺田 騰, 遠西 大輔, 西森 久和, 藤井 敬子, 松岡 賢市, 前田 嘉信

    日本血液学会学術集会   85回   519 - 519   2023.10

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  • 濃縮クエン酸溶液を使用し抗凝固比の変更を行ったアフェレーシスの安全性と有効性に関する後方視的解析

    藤井 敬子, 福見 拓也, 阿部 将也, 浦田 知宏, 清家 圭介, 藤原 英晃, 淺田 騰, 遠西 大輔, 西森 久和, 松岡 賢市, 藤井 伸治, 鷲尾 佳奈, 前田 嘉信

    日本血液学会学術集会   85回   687 - 687   2023.10

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  • Haplo-HCT時代における血栓性微小血管症の影響と予後

    近藤 歌穂, 藤原 英晃, 寺尾 俊紀, 上田 弥生, 久保田 紗矢, 林野 健太, 松原 千哲, 藤原 加奈子, 鴨井 千尋, 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   685 - 685   2023.10

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  • ネララビン関連重症神経障害 単一施設での同種造血幹細胞移植にまつわる4症例

    藤原 加奈子, 藤原 英晃, 久保田 紗矢, 上田 弥生, 林野 健太, 近藤 歌穂, 松原 千哲, 寺尾 俊紀, 木村 真衣子, 清家 圭介, 淺田 騰, 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   1268 - 1268   2023.10

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  • 当院におけるB細胞リンパ腫に対する同種造血幹細胞移植の治療成績

    林野 健太, 西森 久和, 久保田 紗矢, 上田 弥生, 藤原 加奈子, 近藤 歌穂, 松原 千哲, 寺尾 俊紀, 北村 亘, 鴨井 千尋, 清家 圭介, 藤原 英晃, 淺田 騰, 遠西 大輔, 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   1123 - 1123   2023.10

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  • Negative Prognostic Impact of High-Dose or Long-Term Corticosteroid Use in Patients with Relapsed or Refractory B-Cell Lymphoma Who Received Tisagenlecleucel. Reviewed International journal

    Toshiki Terao, Wataru Kitamura, Nobuharu Fujii, Noboru Asada, Chihiro Kamoi, Kanako Fujiwara, Kaho Kondo, Chisato Matsubara, Kenta Hayashino, Keisuke Seike, Hideaki Fujiwara, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

    Transplantation and cellular therapy   29 ( 9 )   573.e1-573.e8   2023.7

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    The prognostic impact of corticosteroid therapy in patients receiving tisagenlecleucel (tisa-cel) treatment who are more likely to develop cytokine release syndrome (CRS) remains unclear. This study aimed to evaluate the clinical impact and lymphocyte kinetics of corticosteroid administration for CRS in 45 patients with relapsed and/or refractory B-cell lymphoma treated with tisa-cel. This was a retrospective evaluation of all consecutive patients diagnosed with relapsed and/or refractory diffuse large B-cell lymphoma, follicular lymphoma with histologic transformation to large B-cell lymphoma, or follicular lymphoma who received commercial-based tisa-cel treatment. The best overall response rate, complete response rate, median progression-free survival (PFS), and median overall survival (OS) were 72.7%, 45.5%, 6.6 months, and 15.3 months, respectively. CRS (predominantly grade 1/2) occurred in 40 patients (88.9%), and immune effector cell-associated neurotoxicity syndrome (ICANS) of all grades occurred in 3 patients (6.7%). No grade ≥3 ICANS occurred. Patients with high-dose (≥524 mg, methylprednisolone equivalent; n = 12) or long-term (≥8 days; n = 9) corticosteroid use had inferior PFS and OS to patients with low-dose or no corticosteroid use (both P < .05). The prognostic impact remained even in 23 patients with stable disease (SD) or progressive disease (PD) before tisa-cel infusion (P = .015). but not in patients with better disease status (P = .71). The timing of corticosteroid initiation did not have a prognostic impact. Multivariate analysis identified high-dose corticosteroid use and long-term corticosteroid use as independent prognostic factors for PFS and OS, respectively, after adjusting for elevated lactate dehydrogenase level before lymphodepletion chemotherapy and disease status (SD or PD). Lymphocyte kinetics analysis demonstrated that after methylprednisolone administration, the proportions of regulatory T cells (Tregs), CD4+ central memory T (TCM) cells, and natural killer (NK) cells were decreased, whereas the proportion of CD4+ effector memory T (TEM) cells was increased. Patients with a higher proportion of Tregs at day 7 had a lower incidence of CRS, but this did not affect prognosis, indicating that early elevation of Tregs may serve as a biomarker for CRS development. Furthermore, patients with higher numbers of CD4+ TCM cells and NK cells at various time points had significantly better PFS and OS, whereas the number of CD4+ TEM cells did not impact prognostic outcomes. This study suggests that high-dose or long-term corticosteroid use attenuates the efficacy of tisa-cel, especially in patients with SD or PD. Additionally, patients with high levels of CD4+ TCM cells and NK cells after tisa-cel infusion had longer PFS and OS.

    DOI: 10.1016/j.jtct.2023.06.018

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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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  • 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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  • 当院における再発難治性びまん性大細胞型B細胞性リンパ腫に対するtisagenlecleucelの治療成績

    北村 亘, 藤井 伸治, 鴨井 千尋, 阿部 将也, 住居 優一, 浦田 知宏, 谷 勝真, 高木 尚江, 山本 晃, 清家 圭介, 藤原 英晃, 淺田 騰, 遠西 大輔, 西森 久和, 藤井 敬子, 松岡 賢市, 前田 嘉信

    日本輸血細胞治療学会誌   69 ( 2 )   331 - 331   2023.4

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  • 当院における再発難治性びまん性大細胞型B細胞性リンパ腫に対するtisagenlecleucelの治療成績

    北村 亘, 藤井 伸治, 鴨井 千尋, 阿部 将也, 住居 優一, 浦田 知宏, 谷 勝真, 高木 尚江, 山本 晃, 清家 圭介, 藤原 英晃, 淺田 騰, 遠西 大輔, 西森 久和, 藤井 敬子, 松岡 賢市, 前田 嘉信

    日本輸血細胞治療学会誌   69 ( 2 )   331 - 331   2023.4

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  • Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation Reviewed International journal

    Keisuke Seike, Anders Kiledal, Hideaki Fujiwara, Israel Henig, Marina Burgos da Silva, Marcel R.M. van den Brink, Robert Hein, Matthew Hoostal, Chen Liu, Katherine Oravecz-Wilson, Emma Lauder, Lu Li, Yaping Sun, Thomas M. Schmidt, Yatrik M. Shah, Robert R. Jenq, Gregory Dick, Pavan Reddy

    Immunity   56 ( 2 )   353 - 368   2023.2

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    The severity of T cell-mediated gastrointestinal (GI) diseases such as graft-versus-host disease (GVHD) and inflammatory bowel diseases correlates with a decrease in the diversity of the host gut microbiome composition characterized by loss of obligate anaerobic commensals. The mechanisms underpinning these changes in the microbial structure remain unknown. Here, we show in multiple specific pathogen-free (SPF), gnotobiotic, and germ-free murine models of GI GVHD that the initiation of the intestinal damage by the pathogenic T cells altered ambient oxygen levels in the GI tract and caused dysbiosis. The change in oxygen levels contributed to the severity of intestinal pathology in a host intestinal HIF-1α- and a microbiome-dependent manner. Regulation of intestinal ambient oxygen levels with oral iron chelation mitigated dysbiosis and reduced the severity of the GI GVHD. Thus, targeting ambient intestinal oxygen levels may represent a novel, non-immunosuppressive strategy to mitigate T cell-driven intestinal diseases.

    DOI: 10.1016/j.immuni.2023.01.007

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  • Pre-infusion factors predicting early failure after tisagenlecleucel for patients with relapsed/refractory diffuse large B-cell lymphoma: A single institute retrospective analysis Reviewed

    Wataru Kitamura, Nobuharu Fujii, Chihiro Kamoi, Tomohiro Urata, Hiroki Kobayashi, Akira Yamamoto, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Ken-ichi Matsuoka, Yoshinobu Maeda

    Japanese Journal of Transplantation and Cellular Therapy   12 ( 4 )   259 - 267   2023

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    DOI: 10.7889/tct-23-014

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  • Successful haematopoietic progenitor cell collection by plerixafor in combination with reduced dose granulocyte colony‐stimulating factor for severe hypoxemia provoked by high‐dose granulocyte colony‐stimulating factor administration Reviewed

    Yui Kambara, Noboru Asada, Kaori Kondo, Yuichi Sumii, Yuki Fujiwara, Keisuke Seike, Yasuhisa Sando, Kyosuke Saeki, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken‐ichi Matsuoka, Yoshinobu Maeda

    Transfusion Medicine   2022.12

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    DOI: 10.1111/tme.12916

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  • Prevention of non-infectious pulmonary complications after intro-bone marrow stem cell transplantation in mice Reviewed International journal

    Yoshiko Yamasuji-Maeda, Hisakazu Nishimori, Keisuke Seike, Akira Yamamoto, Hideaki Fujiwara, Taiga Kuroi, Kyosuke Saeki, Haruko Fujinaga, Sachiyo Okamoto, Ken-Ichi Matsuoka, Nobuharu Fujii, Takehiro Tanaka, Masahiro Fujii, Katsumi Mominoki, Takuro Kanekura, Yoshinobu Maeda

    PloS one   17 ( 9 )   e0273749   2022.11

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    Non-infectious pulmonary complications including idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans syndrome (BOS), which are clinical and diagnostic manifestations of lung chronic graft-versus-host disease (GVHD), cause significant mortality after allogeneic stem cell transplantation (SCT). Increasing evidence suggests that alloantigen reactions in lung tissue play a central role in the pathogenesis of IPS and BOS; however, the mechanism is not fully understood. Several clinical and experimental studies have reported that intra-bone marrow (IBM)-SCT provides high rates of engraftment and is associated with a low incidence of acute GVHD. In the present study, allogeneic SCT was conducted in mouse models of IPS and BOS, to compare intravenous (IV)-SCT with IBM-SCT. Allogeneic IBM-SCT improved the clinical and pathological outcomes of pulmonary complications compared to those of IV-SCT. The mechanisms underlying the reductions in pulmonary complications in IBM-SCT mice were explored. The infiltrating lung cells were mainly CD11b+ myeloid and CD3+ T cells, in the same proportions as in transplanted donor cells. In an in vivo bioluminescence imaging, a higher proportion of injected donor cells was detected in the lung during the early phase (1 h after IV-SCT) than after IBM-SCT (16.7 ± 1.1 vs. 3.1 ± 0.7 × 105 photons/s/animal, IV-SCT vs. IBM-SCT, P = 1.90 × 10-10). In the late phase (5 days) after SCT, there were also significantly more donor cells in the lung after IV-SCT than after IBM-SCT or allogeneic-SCT (508.5 ± 66.1 vs. 160.1 ± 61.9 × 106 photons/s/animal, IV-SCT vs. IBM-SCT, P = 0.001), suggesting that the allogeneic reaction induces sustained donor cell infiltration in the lung during the late phase. These results demonstrated that IBM-SCT is capable of reducing injected donor cells in the lung; IBM-SCT decreases donor cell infiltration. IBM-SCT therefore represents a promising transplantation strategy for reducing pulmonary complications, by suppressing the first step in the pathophysiology of chronic GVHD.

    DOI: 10.1371/journal.pone.0273749

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  • Rearrangement of T Cell genome architecture regulates GVHD Reviewed

    Yaping Sun, Gabrielle Dotson, Lindsey A. Muir, Scott Ronquist, Katherine Oravecz-Wilson, Daniel Peltier, Keisuke Seike, Lu Li, Walter Meixner, Indika Rajapakse, Pavan Reddy

    iScience   25 ( 9 )   104846 - 104846   2022.9

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    DOI: 10.1016/j.isci.2022.104846

    DOI: 10.1101/2021.01.23.427857

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  • A redox cycle with complex II prioritizes sulfide quinone oxidoreductase-dependent H2S oxidation Reviewed

    Roshan Kumar, Aaron P. Landry, Arkajit Guha, Victor Vitvitsky, Ho Joon Lee, Keisuke Seike, Pavan Reddy, Costas A. Lyssiotis, Ruma Banerjee

    Journal of Biological Chemistry   298 ( 1 )   101435 - 101435   2022.1

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    DOI: 10.1016/j.jbc.2021.101435

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  • Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology Reviewed

    Hideaki Fujiwara, Keisuke Seike, Michael D. Brooks, Anna V. Mathew, Ilya Kovalenko, Anupama Pal, Ho-Joon Lee, Daniel Peltier, Stephanie Kim, Chen Liu, Katherine Oravecz-Wilson, Lu Li, Yaping Sun, Jaeman Byun, Yoshinobu Maeda, Max S. Wicha, Thomas L. Saunders, Alnawaz Rehemtulla, Costas A. Lyssiotis, Subramaniam Pennathur, Pavan Reddy

    Nature Immunology   2021.10

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    DOI: 10.1038/s41590-021-01048-3

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  • Characterization of localized macrophages in bronchiolitis obliterans after allogeneic hematopoietic cell transplantation Reviewed

    Taiga Kuroi, Nobuharu Fujii, Koichi Ichimura, Keisuke Seike, Akira Yamamoto, Yui Kambara, Seiichiro Sugimoto, Shinji Otani, Kyosuke Saeki, Hideaki Fujiwara, Hisakazu Nishiomori, Takahiro Oto, Yoshinobu Maeda

    International Journal of Hematology   114 ( 6 )   701 - 708   2021.9

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    DOI: 10.1007/s12185-021-03214-7

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    Other Link: https://link.springer.com/article/10.1007/s12185-021-03214-7/fulltext.html

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

    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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    DOI: 10.1016/j.transci.2021.103147

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  • Total body irradiation-based haploidentical hematopoietic stem cell transplantation using posttransplant cyclophosphamide after administration of inotuzumab ozogamicin: A case report Reviewed

    Masaya Abe, Nobuharu Fujii, Kentaro Mizuhara, Tomohiro Urata, Yuichi Sumii, Yuki Fujiwara, Keisuke Seike, Yasuhisa S, o, Makoto Nakamura, Keiko Fujii, Kyosuke Saeki, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-ichi Matsuoka, Yoshinobu Maeda

    Leukemia Research Reports   15   100241 - 100241   2021

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    DOI: 10.1016/j.lrr.2021.100241

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  • Persistent hypogammaglobulinemia due to immunoglobulin class switch impairment by peri-transplant rituximab therapy Reviewed

    Kentaro Mizuhara, Nobuharu Fujii, Yusuke Meguri, Takahide Takahashi, Michinori Aoe, Makoto Nakamura, Keisuke Seike, Yasuhisa S, o, Keiko Fujii, Masaya Abe, Yuichi Sumii, Tomohiro Urata, Yuki Fujiwara, Kyosuke Saeki, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-ichi Matsuoka, Yoshinobu Maeda

    International Journal of Hematology   112 ( 3 )   422 - 426   2020.9

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    DOI: 10.1007/s12185-020-02886-x

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  • Efficacy of HLA virtual cross‐matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation Reviewed

    Keisuke Seike, Nobuharu Fujii, Naomi Asano, Shigenori Ohkuma, Yasushi Hirata, Keiko Fujii, Yasuhisa Sando, Makoto Nakamura, Kazunori Naito, Kyosuke Saeki, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken‐ichi Matsuoka, Kazuo Tsubaki, Fumio Otsuka, Yoshinobu Maeda

    Transfusion   60 ( 3 )   473 - 478   2020.3

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    DOI: 10.1111/trf.15664

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  • A Long-term Response to Nivolumab in a Case of PD-L1-negative Lung Adenocarcinoma with an EGFR Mutation and Surrounding PD-L1-positive Tumor-associated Macrophages Reviewed

    Hiromi Watanabe, Kadoaki Ohashi, Kazuya Nishii, Keisuke Seike, Go Makimoto, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

    Internal Medicine   58 ( 20 )   3033 - 3037   2019.10

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    DOI: 10.2169/internalmedicine.2875-19

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  • Long-term outcomes in patients treated in the intensive care unit after hematopoietic stem cell transplantation Reviewed

    Makoto Nakamura, Nobuharu Fujii, Kazuyoshi Shimizu, Shuntaro Ikegawa, Keisuke Seike, Tomoko Inomata, Yasuhisa S, o, Keiko Fujii, Hisakazu Nishimori, Ken-ichi Matsuoka, Hiroshi Morimatsu, Yoshinobu Maeda

    International Journal of Hematology   108 ( 6 )   622 - 629   2018.12

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    DOI: 10.1007/s12185-018-2536-x

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  • oligoclonal bands in patients with multiple myeloma: its emergence per se could not be translated to improved survival. Reviewed

    Keisuke Seike

    Cancer science   2014.10

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    The emergence of oligoclonal bands (OB) has been reported in patients with multiple myeloma (MM) after stem cell transplantation (SCT) or successful chemotherapy. However, their clinical relevance remains unclear. We reviewed the clinical records of MM patients from January 2006 to May 2014. Treatment response was evaluated by International Working Group (IMWG) criteria. Serum immunofixation tests were performed at least every 3 months if the patient achieved more than very good partial response (VGPR). Free light chain (FLC) and minimal residual disease measurement by multicolor flow cytometry (MFC) were performed to evaluate the response to treatment. Among the 163 patients included in the study, 40 developed OB. Detection rates of OB in patients with complete response (CR), VGPR and partial response (PR) or less were 51.8, 36.3 and 0%, respectively. Patients with OB showed better progression-free survival (PFS) and overall survival (OS) rates than those without OB (P = 0.028 and P < 0.001, respectively). However, if the patients were limited to ≥VGPR or CR, development of OB did not affect PFS (P = 0.621 and P = 0.646, respectively) or OS (P = 0.189 and P = 0.766, respectively). OB was observed in 60% of patients after SCT, and in 36.6% of patients with more than VGPR without SCT (P < 0.001). Patients with OB tended to have less minimal residual disease than those without OB (P = 0.054) and its presence may affect the stringent CR criteria. In conclusion, the emergence of OB was seen exclusively in patients with favorable responses, but its emergence per se could not be translated to improved survival.

    DOI: 10.1111/cas.12527

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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>
    </jats:sec>

    DOI: 10.1182/blood-2024-202251

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  • Single-Cell DNA Sequencing Reveals Cell-Level Genetic Evolutionary Processes and Clonal Structure in B-Cell Lymphomas

    Hiroyuki Murakami, Ryota Chijimatsu, Hideki Ujiie, Yusuke Naoi, Kazutaka Sunami, Kazuhiko Yamamoto, Soichiro Fujii, Tomofumi Yano, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Nobuharu Fujii, Ken-ichi Matsuoka, Tomohiro Urata, Kazuhiro Ikeuchi, Hiroki Kobayashi, Yasuharu Sato, Shuta Tomida, Yoshinobu Maeda, Daisuke Ennishi

    BLOOD   144   1368 - 1369   2024.11

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    DOI: 10.1182/blood-2024-198983

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  • Single Cell Multi Omics and Spatial Analysis Reveals Plasmablast Signature Malignant Cells As a Key of Intratumor Heterogeneity in Primary Central Nervous System Lymphoma

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    BLOOD   142   2023.11

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    DOI: 10.1182/blood-2023-174410

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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

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  • Tisagenlecleucelのためのリンパ球採取-末梢血CD3+数と採取効率による処理量決定とロングアフェレーシスでの工夫-

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    日本血液学会学術集会抄録(Web)   85th   2023

  • Efficacy of HLA virtual cross-matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation (vol 60, pg 473, 2020)

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    TRANSFUSION   60 ( 11 )   2765 - 2765   2020.11

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    DOI: 10.1111/trf.15872

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  • 造血幹細胞運搬条件設定に関する取り組み

    浅野 尚美, 小郷 博昭, 池田 亮, 閘 結稀, 高木 尚江, 清家 圭介, 三道 康永, 中村 真, 藤井 敬子, 藤井 伸治, 大塚 文男

    日本輸血細胞治療学会誌   66 ( 1 )   78 - 78   2020.2

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  • 自家と同種におけるCD34陽性細胞回収率の違いからみた処理量決定 末梢血幹細胞採取を効率よく終わらせるために

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    日本輸血細胞治療学会誌   65 ( 2 )   349 - 349   2019.4

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  • 抗Fybに加え新たに抗KANNOを産生した1症例

    池田 亮, 小郷 博昭, 浅野 尚美, 閘 結稀, 清家 圭介, 三道 康永, 中村 真, 高木 尚江, 藤井 敬子, 藤井 伸治, 大塚 文男

    日本輸血細胞治療学会誌   64 ( 6 )   829 - 830   2018.12

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  • アルブミン製剤の輸血部管理による使用目的の把握について

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  • Efficacy of HLA-Matched PLT Transfusions for Platelet Transfusion Refractoriness in HSCT Patients

    Keisuke Seike, Nobuharu Fujii, Keiko Fujii, Yasuhisa Sando, Makoto Nakamura, Kyosuke Saeki, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-Ichi Matsuoka, Yoshinobu Maeda

    BLOOD   132   2018.11

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    DOI: 10.1182/blood-2018-99-112365

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  • 造血幹細胞移植における患者指定適合血小板輸血の有効性についての検討(Efficacy of HLA-matched PLT transfusion for platelet transfusion refractoriness in HSCT patients)

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    臨床血液   59 ( 9 )   1541 - 1541   2018.9

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  • 自己血輸血の変遷 貯血式・希釈式・回収式症例数と時代背景を顧みて

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  • 健常人ドナーにおけるクエン酸中毒 CMNCモードとMNCモードで違いがあるのか

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

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    BLOOD   128 ( 22 )   2016.12

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    日本リンパ網内系学会会誌   55   97 - 97   2015.6

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  • 限局期CD5陽性びまん性大細胞型B細胞リンパ腫の治療成績についての検討

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    日本リンパ網内系学会会誌   55   101 - 101   2015.6

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  • 当院において集中治療を要した造血幹細胞移植症例についての検討

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    臨床血液   56 ( 5 )   539 - 539   2015.5

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Research Projects

  • Mitochondria regulates peripheral CD4 CD8 double negative T cells function

    Grant number:23K19469  2023.08 - 2025.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity Start-up

    清家 圭介

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    Grant amount:\2860000 ( Direct expense: \2200000 、 Indirect expense:\660000 )

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  • 同種造血細胞移植後閉塞性細気管支炎におけるマクロファージ標的治療の開発

    Grant number:23K07627  2023.04 - 2026.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    藤井 伸治, 遠西 大輔, 豊岡 伸一, 杉本 誠一郎, 藤原 英晃, 清家 圭介

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

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  • Lecture: Myocardial Infarction (2024academic year) special  - その他

  • Hematology (2024academic year) special  - その他