研究者詳細 - 藤井　敬子

論文 - 藤井　敬子

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Novel method of leukocytapheresis using a highly concentrated sodium citrate solution alternative to acid citrate dextrose solution A 査読国際誌

Masaya Abe, Keiko Fujii, Toshiharu Mitsuhashi, Wataru Kitamura, Kazuhiro Ikeuchi, Takuya Fukumi, Kana Washio, Fumio Otsuka, Yoshinobu Maeda, Nobuharu Fujii

Transfusion 2025年5月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Large-volume leukocytapheresis is time consuming. The upper limit of the inlet flow rate is determined by the inlet: anticoagulant (AC) ratio and can be changed by combining the AC with heparin. Here, we devised a protocol to increase the AC ratio using a highly concentrated sodium citrate solution without heparin. STUDY DESIGN AND METHODS: We collected data from 40 consecutive apheresis procedures performed using the Spectra Optia system on 40 donors for allogeneic peripheral blood stem cells between June 2022 and June 2023. We used AC containing 2.2% sodium citrate (normal concentrated sodium citrate [NSC]) and 5.32% sodium citrate (highly concentrated sodium citrate [HSC]). The AC ratios were set to 12:1 and 24:1 for the NSC and HSC, respectively. RESULTS: The processed volume was not different; the maximum inlet flow rate increased, the total processing time was reduced, the AC solution used was reduced, and the product volume was reduced in the HSC group, compared to the NSC group. Although the CD34+ cell CE2 was reduced in the HSC group, no difference was observed in the number of collected CD34+ cells. The incidences of citrate-related reactions were similar. DISCUSSION: We propose a novel leukocytapheresis method using HSC that shortens the procedure time and reduces the amount of AC solution used compared to the conventional method.

DOI： 10.1111/trf.18280

Markedly elevated serum level of presepsin in agranulocytosis with hematologic malignancy: A potential prognostic factor in a single-institution retrospective study after granulocyte transfusion. 査読国際誌

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年3月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

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

A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD. 査読国際誌

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年2月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

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

Oral calcium supplementation versus placebo in mitigating citrate reactions during apheresis: an open-label randomized control trial 査読国際誌

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年12月

Low platelet counts and low CD4/CD8 ratios at apheresis increase the risk of CAR-T cell manufacturing failure in myeloma 査読

Tomoyasu Jo, Kyoko Yoshihara, Masaki Ri, Nobuhiro Tsukada, Naoya Mimura, Keiko Fujii, Kentaro Fukushima, Shin-ichiro Fujiwara, Yuji Shimura, Kyoko Haraguchi, Koji Kato, Atsushi Satake, Akiyo Yoshida, Rikio Suzuki, Junko Ikemoto, Keita Iwaki, Wataru Takeda, Noboru Yonetani, Ryuji Tanosaki, Minami Yamada-Fujiwara, Kaoru Kahata, Tokiko Nagamura-Inoue, Satoshi Yoshihara, Yasuyuki Arai

Blood Neoplasia 100051 - 100051 2024年10月

Collection efficiency and safety of large-volume leukapheresis for the manufacturing of tisagenlecleucel. 査読国際誌

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年2月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

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

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. 査読国際誌

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年10月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

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

Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch 査読国際誌

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年6月

Risk factors for <scp>CAR‐T</scp> cell manufacturing failure among <scp>DLBCL</scp> patients: A nationwide survey in Japan 査読国際誌

Tomoyasu Jo, Satoshi Yoshihara, Yoshiki Okuyama, Keiko Fujii, Tomoko Henzan, Kaoru Kahata, Rie Yamazaki, Wataru Takeda, Yoshihiro Umezawa, Kentaro Fukushima, Takashi Ashida, Minami Yamada‐Fujiwara, Ryo Hanajiri, Noboru Yonetani, Yuma Tada, Yuji Shimura, Hidekazu Nishikii, Norio Shiba, Naoya Mimura, Jun Ando, Takayuki Sato, Yasuhiro Nakashima, Junko Ikemoto, Keita Iwaki, Shin‐ichiro Fujiwara, Masaki Ri, Tokiko Nagamura‐Inoue, Ryuji Tanosaki, Yasuyuki Arai

British Journal of Haematology 2023年4月

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 <scp>COBE</scp> spectra and the spectra Optia systems 査読国際誌

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 62 ( 9 ) 1829 - 1838 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

BACKGROUND: For pediatric recipients, red blood cells (RBCs) are added to bone marrow (BM) collections before low RBC volume BM processing using COBE Spectra (COBE) or Spectra Optia (Optia). However, the processing efficiency of this approach has not been evaluated. This study aimed to evaluate RBC depletion and nucleated cell subpopulation recovery rates in third-party RBC-manipulated BM products processed with the COBE or Optia. STUDY DESIGN AND METHODS: We retrospectively collected data on RBC depletion from low RBC volume BM with third-party RBCs (manipulated group) and on conventional large-volume, BM (unmanipulated group) processing performed between September 2010 and December 2021. All procedures were performed using COBE or Optia. RESULTS: The median residual RBC volume in the manipulated group was 9.5 ml in COBE and 2.5 ml in Optia (p = .01). The median total nucleated cell (TNC) and mononuclear cell (MNC) were comparable between the manipulated groups using each cell separator (TNC, 40.8 vs. 47.1%; MNC, 78.3 vs. 79.4%). The manipulation did not adversely affect TNC and MNC recoveries in either device. In addition, Optia achieved similar CD34+ cell recovery to that in large-BM-volume processing using the same device (147.5 vs. 184.5%, p = .112). During a follow-up period, neutrophil engraftment was achieved in all patients who received third-party RBC-manipulated grafts, and platelet engraftment was achieved in all cases, except one. CONCLUSION: The addition of third-party RBC to low RBC volume BM collections from or for pediatric patients does not have any negative impact on either RBC depletion or hematopoietic cell recovery during processing with the widely used cell separator.

DOI： 10.1111/trf.17039

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/trf.17039

Successful neutrophil engraftment supported by granulocyte transfusion in adult allogeneic transplant patients with peri-transplant active infection 査読国際誌

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年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

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

Low hematocrit reduces the efficiency of CD34+ cell collection when using the Spectra Optia continuous mononuclear cell collection procedure 査読国際誌

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

2022年3月

骨髄濃縮時にみられたチャネル内の脂肪層分離と細胞凝集査読

藤井敬子, 住居優一, 浦田知宏, 木村真衣子, 近藤匠, 藤井伸治

日本輸血細胞治療学会誌 68 ( 1 ) 1 - 2 2022年2月

Effectiveness of supplemental oral calcium drink in preventing citrate-related adverse effects in peripheral blood progenitor cell collection 査読国際誌

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

Transfusion and Apheresis Science 60 ( 4 ) 103147 - 103147 2021年8月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

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

新しい全自動型血液成分分離装置Spectra Optia®を用いた末梢血幹細胞採取―COBE Spectra®と比較して― 査読

藤井敬子, 藤井伸治, 淺田騰, 西森久和, 狩山由貴, 池田亮, 浅野尚美, 小郷博昭, 岩月啓氏

日本輸血・細胞治療学会 59 ( 6 ) 799 - 804 2013年

担当区分：筆頭著者記述言語：日本語出版者・発行元：The Japan Society of Transfusion Medicine and Cell Therapy

Spectra Optia^®は，COBE Spectra^®に代わる次世代機であり，自動インターフェイス管理（AIM）システムを採用し全自動的にアフェレーシスを行うことができる．主に臨床使用経験が積まれていた欧州に対し，わが国では2011年7月に認可され今後の使用実績が期待される．<br> 今回，末梢血幹細胞採取におけるSpectra Optia^®（Optia）とCOBE Spectra^®（COBE）の比較を目的として，当院におけるOptia導入前後での末梢血幹細胞採取73件について，機器別採取結果を後方視的に検討した．採取回数はOptia群24回（自家15回，同種9回），COBE群49回（自家36回，同種13回），処理血液量は自家で患者体重（kg）当たり150ml，同種はドナー体重（kg）当たり200mlとした．<br> 単核球回収率は両機種間で有意差はなかったが，採取産物容量，赤血球混入量はOptia群で有意に少なかった．また同種のみで比較した場合，Optia群では採取産物中の血小板混入数が有意に少なかった．副作用面でも重篤なものはなく，血漿成分が過剰に採取されない簡便な全自動型血液成分分離装置としてOptiaは期待できるものと考えられた．<br>

DOI： 10.3925/jjtc.59.799

その他リンク： http://search.jamas.or.jp/link/ui/2014217196

Elevation of serum hepatocyte growth factor during granulocyte colony-stimulating factor-induced peripheral blood stem cell mobilization. 査読国際誌

Fujii K, Ishimaru F, Kozuka T, Matsuo K, Nakase K, Kataoka I, Tabayashi T, Shinagawa K, Ikeda K, Harada M, Tanimoto M

Br J Haematol 124 ( 2 ) 190 - 194 2004年1月

Over-expression of short isoforms of Helios in patients with adult T-cell leukaemia/lymphoma 査読国際誌

FUJII K

BrJ Haematol 120 ( 6 ) 986 - 989 2003年3月

Myelodysplastic neoplasms with repeating TAFRO syndrome-like symptoms. 査読

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年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

A fatal case of enterovirus A71-induced meningoencephalitis following allogenic hematopoietic stem cell transplantation. 査読国際誌

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年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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

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年1月

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

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年

記述言語：日本語掲載種別：研究論文（学術雑誌）

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

Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease

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 Journal 2024年12月

掲載種別：研究論文（学術雑誌）出版者・発行元：American Society of Hematology

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

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

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年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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

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年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

Activated CD4<sup>+</sup> T Cell Proportion in the Peripheral Blood Correlates with the Duration of Cytokine Release Syndrome and Predicts Clinical Outcome after Chimeric Antigen Receptor T Cell Therapy 査読

Wataru Kitamura, Noboru Asada, Shuntaro Ikegawa, Hideaki Fujiwara, Chihiro Kamoi, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-ichi Matsuoka, Yoshinobu Maeda

Internal Medicine 63 ( 13 ) 1863 - 1872 2024年7月

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 査読

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年6月

掲載種別：研究論文（学術雑誌）出版者・発行元：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

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細胞リンパ腫査読

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年5月

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

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 119 ( 4 ) 459 - 464 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Although chimeric antigen receptor T-cell (CAR-T) therapies have dramatically improved the outcomes of relapsed/refractory B-cell malignancies, recipients suffer from severe humoral immunodeficiencies. Furthermore, patients with coronavirus disease 2019 (COVID-19) have a poor prognosis, as noted in several case reports of recipients who had COVID-19 before the infusion. We report the case of a 70-year-old woman who developed COVID-19 immediately before CAR-T therapy for high-grade B-cell lymphoma. She received Tixagevimab-Cilgavimab chemotherapy and radiation therapy but never achieved remission. She was transferred to our hospital for CAR-T therapy, but developed COVID-19. Her symptoms were mild and she was treated with long-term molnupiravir. On day 28 post-infection, lymphodepleting chemotherapy was restarted after a negative polymerase chain reaction (PCR) test was confirmed. The patient did not experience recurrence of COVID-19 symptoms or severe cytokine release syndrome. Based on the analysis and comparison of the previous reports with this case, we believe that CAR-T therapy should be postponed until a negative PCR test is confirmed. In addition, Tixagevimab-Cilgavimab and long term direct-acting antiviral agent treatment can be effective prophylaxis for severe COVID-19 and shortening the duration of infection.

DOI： 10.1007/s12185-024-03711-5

Clinical significance of gynecological examinations in long-term follow-ups 査読

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年

Recurrent Cerebral Hemorrhaging with Platelet Dysfunction Accompanied by Anti-glycoprotein VI Autoantibodies in a Patient with TAFRO Syndrome. 査読

Akira Yamamoto, Hisakazu Nishimori, Toshiaki Shirai, Katsuhiro Takano, Aya Komura, Yui Kambara, Takuya Fukumi, Tomohiro Urata, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Kenji Niiya, Katsue Suzuki-Inoue, Yoshinobu Maeda

Internal medicine (Tokyo, Japan) 63 ( 13 ) 1917 - 1922 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

Thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly (TAFRO) syndrome is an inflammatory disorder with an unclear pathogenesis. We herein report a case of TAFRO syndrome in remission in a patient who experienced recurrent intracranial bleeding despite a normal platelet count and coagulation system. A further investigation suggested the presence of anti-glycoprotein VI (GPVI) autoantibodies in the plasma, which induced platelet dysfunction and bleeding tendency. No new bleeding or relapse of TAFRO syndrome occurred after immunosuppressive therapy was initiated. These findings may help elucidate the autoimmune pathogenesis of TAFRO syndrome.

DOI： 10.2169/internalmedicine.2799-23

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

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年

記述言語：日本語掲載種別：研究論文（学術雑誌）

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

Distribution and clinical impact of molecular subtypes with Dark Zone signature of DLBCL in a Japanese real-world study. 査読国際誌

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年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

Negative Prognostic Impact of High-Dose or Long-Term Corticosteroid Use in Patients with Relapsed or Refractory B-Cell Lymphoma Who Received Tisagenlecleucel. 査読国際誌

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年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T-cell therapy. 査読国際誌

Wataru Kitamura, Noboru Asada, Yusuke Naoi, Masaya Abe, Hideaki Fujiwara, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Tadashi Yoshino, Yoshinobu Maeda

British journal of haematology 202 ( 2 ) 294 - 307 2023年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Mechanisms of prolonged cytopenia (PC) after chimeric antigen receptor (CAR) T-cell therapy, an emerging therapy for relapsed or refractory diffuse large B-cell lymphoma, remain elusive. Haematopoiesis is tightly regulated by the bone marrow (BM) microenvironment, called the 'niche'. To investigate whether alterations in the BM niche cells are associated with PC, we analysed CD271+ stromal cells in BM biopsy specimens and the cytokine profiles of the BM and serum obtained before and on day 28 after CAR T-cell infusion. Imaging analyses of the BM biopsy specimens revealed that CD271+ niche cells were severely impaired after CAR T-cell infusion in patients with PC. Cytokine analyses after CAR T-cell infusion showed that CXC chemokine ligand 12 and stem cell factor, niche factors essential for haematopoietic recovery, were significantly decreased in the BM of patients with PC, suggesting reduced niche cell function. The levels of inflammation-related cytokines on day 28 after CAR T-cell infusion were consistently high in the BM of patients with PC. Thus, we demonstrate for the first time that BM niche disruption and sustained elevation of inflammation-related cytokines in the BM following CAR T-cell infusion are associated with subsequent PC.

DOI： 10.1111/bjh.18747

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輸注後の早期再燃を予測する輸注前因子の検討査読

北村亘, 藤井伸治, 鴨井千尋, 浦田知宏, 小林宏紀, 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

日本造血・免疫細胞療法学会雑誌 12 ( 4 ) 259 - 267 2023年

急性リンパ性白血病に対するtisagenlecleucel製造効果-日本輸血・細胞治療学会CAR-Tタスクフォースによる研究－査読

64 ( 5 ) 331 - 337 2023年

Bilateral Lacrimal Gland Mantle Cell Lymphoma in 11-Year Follow-Up: Case Report and Review of 48 Cases With Ocular Adnexal Presentation in the Literature. 査読国際誌

Toshihiko Matsuo, Takehiro Tanaka, Kazuya Okada, Kenji Notohara, Keiko Fujii, Nobuharu Fujii

Journal of investigative medicine high impact case reports 11 23247096231185483 - 23247096231185483 2023年

記述言語：英語掲載種別：研究論文（学術雑誌）

A 63-year-old woman, with 11-year history of breast cancer, showed bilateral lacrimal gland enlargement on magnetic resonance imaging. Gallium-67 scintigraphy, as the standard at that time in 2004, demonstrated abnormally high uptake only in bilateral lacrimal glands. The lacrimal glands were extirpated and the pathological diagnosis was mantle cell lymphoma (MCL). She underwent bilateral orbital radiation, based on no uptake of gallium-67 in other sites of the body. In a month, bone marrow biopsy revealed the infiltration with MCL, positive for cyclin D1. She showed hepatic lymphadenopathy and splenomegaly, and so received 2 cycles of alternating Hyper-CVAD therapy and high-dose methotrexate with cytarabine, combined with rituximab, in 2 months, leading to complete remission. She underwent autologous peripheral blood stem cell transplantation and was well until the age of 68 years when she showed a recurrent intratracheal submucosal lesion of lymphoma and underwent one course of reduced-dose CHOP combined with rituximab. Next year, the left rib resection revealed the metastasis of breast adenocarcinoma, leading to daily oral letrozole. Further 2 years later, computed tomographic scan demonstrated multiple submucosal nodular lesions in the trachea and bronchi, together with cervical and supraclavicular lymphadenopathy, and intratracheal lesion biopsy and bone marrow biopsy proved the involvement with MCL. She underwent 2 courses of bendamustine and rituximab, resulting in complete remission but died of metastatic breast cancer at the age of 74 years. Clinical features in 48 previous cases with ocular adnexal MCL in the literature were summarized in this study.

DOI： 10.1177/23247096231185483

Early initiation of low-dose gilteritinib maintenance improves posttransplant outcomes in patients with R/R FLT3mut AML. 査読国際誌

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年12月

Association between early corticosteroid administration and long-term survival in non-infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation. 査読

Yui Kambara, Nobuharu Fujii, Yoshiaki Usui, Akira Yamamoto, Hisao Higo, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

International journal of hematology 117 ( 4 ) 578 - 589 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Non-infectious pulmonary complications (NIPCs) after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with poor outcomes. It is important to maximize the effectiveness of primary treatment because secondary treatment has not been established. We analyzed data from 393 patients who underwent allogeneic HSCT during a 10-year period. Thirty-seven were diagnosed with NIPCs, which consisted of idiopathic pneumonia syndrome, bronchiolitis obliterans, and interstitial lung disease including cryptogenic organizing pneumonia. Among these, 18 died (Dead group) while 19 remained alive (Alive group) during the study period. The median time between NIPC diagnosis and first administration of ≥ 1 mg/kg/day corticosteroids (prednisolone dose equivalent) was significantly longer in the Dead group than the Alive group, at 9 days versus 4 days (p = 0.01). We further divided these cases into those who received prednisolone within seven days and after 8 days. We found that the ≤ 7 days group were more likely to survive after their NIPC diagnosis compared to the ≥ 8 days group (p = 0.06). Our analysis showed that early initiation of corticosteroid therapy is associated with long-term survival in NIPCs.

DOI： 10.1007/s12185-022-03517-3

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. 査読国際誌

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 (Oxford, England) 2022年9月

CD19 immunostaining of a stored paraffin-embedded vitrectomy cell block of intraocular lymphoma contributing to chimera antigen receptor T-cell therapy. 査読

Matsuo T, Tanaka T, Fujii N, Fujii K, Kondo E

Journal of Clinical and Experimental Hematopathology 62 ( 3 ) 187 - 189 2022年8月

Tisagenlecleucel投与後のステロイド抵抗性CRSに対し、cyclophosphamide投与を行い改善が得られた1例査読

守山喬史, 藤原英晃, 村上裕之, 松村彰文, 大山矩史, 淺田騰, 西森久和, 藤井敬子, 藤井伸治, 遠西大輔, 末次慶收, 松岡賢市, 前田嘉信

臨床血液 63 ( 6 ) 685 - 685 2022年6月

Analysis of Immunity against Measles, Mumps, Rubella, and Varicella Zoster in Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience. 査読

Shohei Yoshida, Nobuharu Fujii, Chihiro Kamoi, Wataru Kitamura, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Keiko Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

Acta medica Okayama 76 ( 3 ) 247 - 253 2022年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Vaccine-preventable disease (VPD) infections are more severe in immunocompromised hosts. Vaccination against measles, mumps, rubella, and varicella zoster (VZV) (MMRV) is therefore recommended for hematopoietic stem cell transplantation (HCT) recipients. However, studies on adult HCT recipients with VPD infections are limited. At our institution, we have systematically conducted serological MMRV tests as a part of check-up examinations during long-term follow-up (LTFU) after HCT since 2015. This retrospective study aimed to evaluate changes in the serostatus between before and 2 years after allogeneic HCT. Among 161 patients, the pre-transplant seropositivity was 82.7% for measles, 86.8% for mumps, 84.2% for rubella, and 94.3% for VZV. Among 56 patients who underwent LTFU including serological MMRV tests at 2 years after HCT, the percentages maintaining seroprotective antibody levels for measles, mumps, rubella and VZV were 71.5% (40/56), 51.8% (29/56), 48.2% (27/56), and 60.7% (34/56), respectively. Vaccination was recommended for 22 patients, and 12 were vaccinated. Among the 12 vaccinated patients, rates of seroconversion were examined in 2-6 patients for each of the four viruses. They were 100% (3/3) for measles, 33.3% (1/3) for mumps, 50% (3/6) for rubella, and 0% (0/2) for VZV. Further studies are warranted to clarify the effect of vaccination in adult HCT recipients.

DOI： 10.18926/AMO/63718

Chronic active Epstein–Barr virus infection presenting as refractory chronic sinusitis 査読

Wataru Kitamura, Hideaki Fujiwara, Akifumi Matsumura, Takaya Higaki, Rei Shibata, Tomohiro Toji, Soichiro Fujii, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-ichi Matsuoka, Tadashi Yoshino, Yoshinobu Maeda

International Journal of Hematology 2022年2月

Possible prognostic impact of WT1 mRNA expression at day + 30 after haploidentical peripheral blood stem cell transplantation with posttransplant cyclophosphamide for patients with myeloid neoplasm: a multicenter study from the Okayama Hematological Study Group 査読

Wataru Kitamura, Nobuharu Fujii, Yuichiro Nawa, Keigo Fujishita, Hiroyuki Sugiura, Takanori Yoshioka, Yuki Fujiwara, Yoshiaki Usui, Keiko Fujii, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Ken-ichi Matsuoka, Yoshinobu Maeda

International Journal of Hematology 115 ( 4 ) 515 - 524 2022年2月

Sequential Combination of FLAM and Venetoclax plus Azacitidine to Bridge to Cord Blood Transplantation in a Patient with Primary Induction Failure Acute Myeloid Leukemia. 査読国際誌

Hiroyuki Murakami, Ken-Ichi Matsuoka, Takeru Asano, Takashi Moriyama, Akifumi Matsumura, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Tomohiro Toji, Tadashi Yoshino, Yoshinobu Maeda

Case reports in oncology 15 ( 3 ) 974 - 979 2022年

記述言語：英語

Venetoclax (VEN) is an oral B-cell lymphoma-2 (BCL-2) inhibitor that has been widely used to treat various hematological disorders. Recent studies have demonstrated that VEN in combination with fludarabine-enhanced high-dose cytarabine (FLA) is effective for treating relapsed or refractory acute myeloid leukemia (AML). In the combination therapy, salvage chemotherapy and VEN are basically concurrently administrated; however, further optimization may enable the treatment to apply to larger numbers of patients with various clinical backgrounds. Here, we describe a case of refractory AML treated with a sequential combination of the intensive chemotherapy (fludarabine, cytarabine, and mitoxantrone; FLAM) and VEN/AZA to bridge to an unrelated cord blood transplantation (uCBT). By continuously adding VEN/AZA after FLAM, the patient achieved morphologic leukemia free state with only minor toxicities. Blood cell counts did not recover until the time of transplantation because of the deep myelosuppression caused by the treatment sequence, but the infection risk was safely managed during this period. After engraftment, maintenance therapy with VEN/AZA was performed, and the patient has survived without disease recurrence for over 9 months after transplantation. Our case suggests that bridging therapy with VEN and AZA from the time of the last chemotherapy to allogeneic transplantation may provide an effective and tolerable treatment strategy for refractory AML. Further studies of larger numbers of cases are needed to validate the effectiveness of this treatment.

DOI： 10.1159/000526697

Nodal Peripheral T-cell Lymphoma with T Follicular Helper Phenotype Presenting as Chorea During Treatment: A Case Report and Literature Review. 査読

Wataru Kitamura, Daisuke Ennishi, Ryoya Yukawa, Ryo Sasaki, Chikamasa Yoshida, Hiroki Takasuka, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Koji Abe, Tadashi Yoshino, Yoshinobu Maeda

Internal medicine (Tokyo, Japan) 60 ( 19 ) 3155 - 3160 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 72-year-old man presented with chorea while undergoing treatment for recurrence of nodal peripheral T-cell lymphoma with T follicular helper (TFH) phenotype. An examination by brain N-isopropyl-p-iodoamphetamine (123I-IMP)-single photon emission computed tomography (SPECT) revealed no abnormalities other than a decreased cerebral blood flow (CBF) in the left striatum. After four courses of salvage chemotherapy, his clinical symptoms and asymmetric cerebral perfusion improved, suggesting that the decreased CBF had caused chorea. The significance of brain SPECT has not been fully clarified in patients with chorea-associated malignant lymphoma, warranting further investigations. Brain SPECT is an alternative approach to identify abnormalities in such patients.

DOI： 10.2169/internalmedicine.7180-21

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査読

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年6月

Effects of Gram-negative Rod Blood Stream Infection on Acute GVHD in Allogeneic Hematopoietic Stem Cell Transplantation: A Single-institute Analysis. 査読

Masaaki Nishinohara, Hisakazu Nishimori, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Ken-Ichi Matsuoka, Keiko Fujii, Nobuharu Fujii, Yoshinobu Maeda

Acta medica Okayama 75 ( 3 ) 279 - 287 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

A bloodstream infection (BSI) is the most common serious infectious complication of hematopoietic stem cell transplantation (HSCT). BSI promotes an inflammatory state, which exacerbates acute graft-versus-host disease (GVHD). We investigated whether a Gram-negative rod bloodstream infection (GNR-BSI), which develops early after allo-HSCT, affected the onset or exacerbated acute GVHD in 465 patients who underwent allo-HSCT from 1995 through 2015 at a single institution. Eighty-eight patients (19%) developed BSI during the study period. Among the cultures, 50 (57%) were Gram-positive cocci (GPC) and 31 (35%) were GNR. Of the 465 patients, 187 (40%) developed acute GVHD of grade II or higher within the first 100 days post-allogeneic HSCT: 124 (27%) had acute GVHD grade II, 47 (10%) had grade III, and 16 (3%) had grade IV. Multivariate analysis revealed that GNR-BSI was a significant risk factor for grade II-IV acute GVHD (grade II-IV: hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.03-2.97; grade III-IV: HR 2.37, 95% CI 1.03-5.43). These results suggest that GNR-BSI may predict the onset and exacerbation of acute GVHD.

DOI： 10.18926/AMO/62219

Successful Treatment of Acute Promyelocytic Leukemia Complicated with Endometrial Cancer by Arsenic Trioxide. 査読

Hiroyuki Sugiura, Hisakazu Nishimori, Hirofumi Matsuoka, Keiichiro Nakamura, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshinobu Maeda

Acta medica Okayama 75 ( 2 ) 219 - 224 2021年4月

記述言語：英語

Acute promyelocytic leukemia (APL) is a hematological emergency that requires urgent intervention because of the high incidence of early hemorrhagic death. When patients with APL experience a synchronous solid organ tumor, the tumor's treatment must also be done properly. Differentiation-inducing therapy using arsenic trioxide (ATO) has less hematological toxicity compared to cytotoxic chemotherapy and might be preferable for untreated APL patients with a synchronous solid organ tumor. Here we describe the first successful case of untreated APL and synchronous endometrial cancer (in an adult Japanese woman) treated with ATO consolidation therapy and the subsequent surgery and chemotherapy for endometrial cancer.

DOI： 10.18926/AMO/61904

Author Correction: 5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy. 査読国際誌

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 ) 6420 - 6420 2021年3月

Pretransplant nivolumab further enhanced Treg expansion after posttransplant cyclophosphamide; another aspect for immune tolerance by PTCy after nivolumab. 査読国際誌

Shuntaro Ikegawa, Yusuke Meguri, Kentaro Mizuhara, Takuya Fukumi, Hiroki Kobayashi, Yuichi Sumii, Takumi Kondo, Yasuhisa Sando, 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年3月

Total body irradiation-based haploidentical hematopoietic stem cell transplantation using posttransplant cyclophosphamide after administration of inotuzumab ozogamicin: A case report. 査読国際誌

Masaya Abe, Nobuharu Fujii, Kentaro Mizuhara, Tomohiro Urata, Yuichi Sumii, Yuki Fujiwara, Keisuke Seike, Yasuhisa Sando, 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年

記述言語：英語

Owing to the poor prognosis of relapsed or refractory acute lymphoblastic leukemia (ALL), hematopoietic stem cell transplantation (HSCT) followed by effective salvage therapy is required. Inotuzumab ozogamicin (INO) was developed for ALL refractory to standard chemotherapy. However, previous reports suggest that sinusoidal obstruction syndrome (SOS) risk increases in patients with HSCT receiving INO, especially with dual alkylating agents. We report a case of relapsed Philadelphia chromosome-negative B-ALL where the patient underwent haploidentical HSCT using fludarabine/total body irradiation conditioning and posttransplant cyclophosphamide. Successful engraftment was achieved without SOS development.

DOI： 10.1016/j.lrr.2021.100241

Allogeneic hematopoietic stem cell transplantation in a prior lung transplant recipient. 査読

Yuki Fujiwara, Ken-Ichi Matsuoka, Miki Iwamoto, Yuichi Sumii, Masaya Abe, Kentaro Mizuhara, Tomohiro Urata, Kyosuke Saeki, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Junichi Sugita, Hajime Kobayashi, Takahiro Oto, Yoshinobu Maeda

International journal of hematology 112 ( 6 ) 871 - 877 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Hematological diseases after solid organ transplant (SOT) are an emerging issue as the number of long-term SOT survivors increases. Expertise in managing patients requiring allogeneic hematopoietic stem cell transplantation (HSCT) after SOT from independent donors is needed; however, clinical reports of HSCT after SOT are limited, and the feasibility and risk are not well understood. In particular, HSCT in prior lung transplant recipients is thought to be complicated as the lung is immunologically distinct and is constantly exposed to the surrounding environment. Herein, we describe a case of successful HSCT in a patient with myelodysplastic syndromes who had previously received a lung transplant from a deceased donor for bronchiolitis obliterans syndrome. Reports about cases of HSCT after lung transplant are quite rare; thus, we discuss the mechanisms of immune tolerance through the clinical course of our case. This case suggests that HSCT after SOT can be considered a therapeutic option in cases where the transplanted organ is functionally retained and the hematological disease is in remission.

DOI： 10.1007/s12185-020-02967-x

Post-transplantation cyclophosphamide restores early B-cell lymphogenesis that suppresses subsequent chronic graft-versus-host disease 査読国際誌

Miki Iwamoto, Shuntaro Ikegawa, Takumi Kondo, Yusuke Meguri, Makoto Nakamura, Yasuhisa Sando, 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 2020年10月

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

Kentaro Mizuhara, Nobuharu Fujii, Yusuke Meguri, Takahide Takahashi, Michinori Aoe, Makoto Nakamura, Keisuke Seike, Yasuhisa Sando, 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年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Post-transplant lymphoproliferative disorder (PTLD) is one of the most serious complications of allogeneic hematopoietic stem cell transplantation (HSCT). Rituximab is effective for PTLD; however, rituximab can produce adverse effects, including hypogammaglobulinemia. Here, we present the case of an 18-year-old female with refractory cytopenia of childhood who developed persistent selective hypogammaglobulinemia with low immunoglobulin G (IgG) 2 and IgG4 levels and monoclonal protein after rituximab therapy against probable PTLD. Despite B-cell recovery, the serum IgG levels gradually declined, reaching < 300 mg/dL at 33 months after rituximab treatment. In addition, class-switched memory (CD27 + IgD -) B cells were limited in phenotypic analysis. These findings suggest that peri-HSCT rituximab may contribute to an abnormal B-cell repertoire induced by impaired immunoglobulin class switch.

DOI： 10.1007/s12185-020-02886-x

その他リンク： http://link.springer.com/article/10.1007/s12185-020-02886-x/fulltext.html

Secondary Pulmonary Alveolar Proteinosis Associated with Primary Myelofibrosis and Ruxolitinib Treatment: An Autopsy Case. 査読

Hiroyuki Sugiura, Hisakazu Nishimori, Kazuya Nishii, Tomohiro Toji, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Koh Nakata, Katsuyuki Kiura, Yoshinobu Maeda

Internal medicine (Tokyo, Japan) 59 ( 16 ) 2023 - 2028 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Pulmonary alveolar proteinosis (PAP) is an uncommon lung disorder characterized by the excessive accumulation of surfactant-derived lipoproteins in the pulmonary alveoli and terminal bronchiole. Secondary PAP associated with primary myelofibrosis (PMF) is extremely rare, and to our knowledge, no autopsy case has been reported. We herein report an autopsy case of secondary PAP occurring in a patient with PMF who was treated with the Janus kinase 1/2 inhibitor ruxolitinib. We confirmed a diagnosis of PAP with complications based on the pathological findings at the autopsy. Notably, this case might suggest an association between ruxolitinib treatment and PAP occurrence.

DOI： 10.2169/internalmedicine.4082-19

Efficacy of HLA virtual cross-matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation 査読

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年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

BACKGROUND Cross-matched platelet (cross-matched PLT) transfusion is effective for immune-mediated platelet transfusion refractoriness (PTR), but is more costly and time-consuming for physical cross-match than using standard PLT units. Recent studies have reported the utility of human leucocyte antigens (HLA) virtual cross-matched PLT (HLA-matched PLT) that is defined as HLA-A/B matched or no antibody against donor-specific antigen. Here, we evaluated the effect of HLA-matched PLTs for PTR in post hematopoietic stem cell transplant (HSCT) recipients. STUDY DESIGN AND METHODS Our study included a total of 241 PLTs in 16 patients who underwent HSCT at Okayama University Hospital between 2010 and 2017, receiving either HLA-matched or cross-matched PLTs. We calculated the 24-hour corrected count increments (CCI-24) to evaluate the effect of PLTs. A CCI-24 >= 4500 was considered to be a successful transfusion. RESULTS We analyzed 139 cross-matched PLTs and 102 HLA-matched PLTs. In the immune-mediated PTR, the rate of successful transfusion was 60.5% for cross-matched PLT and 63.4% for HLA-matched PLT (p = 0.825). On the other hand, the median CCI-24 for cross-matched PLT transfusions and HLA-matched PLT transfusions were 1856 and 5824 (p < 0.001), with a success rate of 28.1 and 54.1% in cases with non-immune-mediated PTR, respectively (p = 0.001). CONCLUSION The effectiveness of HLA-matched PLT is not inferior to cross-matched PLT. This result indicates that physical cross-match can be omitted in post HSCT PTR.

DOI： 10.1111/trf.15664

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

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 10 ( 1 ) 17237 2020年

Macrophage elimination in bone marrow by dexamethasone palmitate is associated with successful engraftment in patients with hemophagocytic syndrome. 査読

Hiroyuki Sugiura, Ken-Ichi Matsuoka, Masayuki Matsuda, Shuntaro Ikegawa, Tomoko Inomata, Taiga Kuroi, Takeru Asano, Shohei Yoshida, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Yoshinobu Maeda

International journal of hematology 110 ( 2 ) 260 - 262 2019年8月

Plasma exchange eliminates residual mogamulizumab but does not warrant prompt recovery of peripheral Treg levels 査読国際誌

Sugiura H, Matsuoka KI, Sando Y, Meguri Y, Ikegawa S, Nakamura M, Iwamoto M, Yoshioka T, Asano T, Kondo E, Fujii K, Fujii N, Maeda Y

Transfusion and Apheresis Science 58 ( 4 ) 472 - 474 2019年7月

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

Okamoto S, Matsuoka KI, Sakamoto M, Usui Y, Fujiwara Y, Kondo T, Tani K, Saeki K, Meguri Y, Asada N, Ennishi D, Nishimori H, Fujii K, Fujii N, Maeda Y

Acta medica Okayama 73 ( 2 ) 161 - 171 2019年4月

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

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

International journal of hematology 108 ( 6 ) 622 - 629 2018年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

The number of patients who are successfully discharged from the intensive care unit (ICU) after hematopoietic stem cell transplantation (HSCT) remains limited. Most previous studies have evaluated short-term outcomes using ICU mortality; there have been comparatively fewer reports of long-term outcomes. We retrospectively analyzed 39 HSCT patients admitted to the ICU for the first time between April 2008 and July 2014. Performance status was evaluated in four long-term survivors in July 2016. Median age at ICU admission was 54 years (range 30-68). In total, 33 patients (70.2%) required mechanical ventilation and 31 patients (66%) required dialysis. The median OS from first ICU admission was 41 days (95% confidence interval [CI]: 22-64) and the 1-year survival rate was 12.8% (95% CI 4.7-25.2). No statistically significant factors were associated with short-term outcomes. Among long-term outcomes, a second or subsequent HSCT and neutropenia at ICU admission were significant risk factors. Four of 10 ICU survivors have survived with good performance status for a median of 1994 (1203-2633) days. Our results suggest that the number of prior transplants and neutropenia at ICU admission may influence OS.

DOI： 10.1007/s12185-018-2536-x

Predictors of vasovagal reactions during preoperative autologous blood donation: a single-institution analysis. 査読

Hisakazu Nishimori, Nobuharu Fujii, Keiko Fujii, Tohru Ikeda, Naomi Asano, Hiroaki Ogo, Miwa Yamakawa, Naoe Takagi, Fumio Otsuka, Kazuma Ikeda

International journal of hematology 105 ( 6 ) 812 - 818 2017年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Studies examining risk factors associated with vasovagal reactions (VVRs) during autologous blood donations, especially in younger subjects, have been limited. The aim of the present study was to define risk factors for VVRs during preoperative autologous blood donation in patients, including those younger than 18 years old. We retrospectively analyzed 4192 autologous, preoperative blood donations between 2007 and 2015 at Okayama University Hospital. Eighty-seven (2.08%) of the patients experienced VVRs. VVRs occurred approximately three times as often in patients 0-17 years old (16/320, 5.0%) than in patients 18 years and older (71/3872, 1.8%). In particular, VVRs occurred more frequently in those 10-13 years old, and decreased with older age (P = 0.006). In a univariate analysis, younger age, lower body mass index, lower systolic blood pressure, lower body weight, lower total blood volume, female gender, first-time collection, and higher heart rate were associated with a higher incidence of VVRs. In a multivariate analysis, lower systolic blood pressure (P < 0.001), higher heart rate (P = 0.007), and first-time collection (P = 0.015), remained independent predictors of VVRs. These results emphasize the need for careful attention during blood collection.

DOI： 10.1007/s12185-017-2204-6

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

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

Cytotherapy 19 ( 4 ) 514 - 520 2017年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

DOI： 10.1016/j.jcyt.2016.12.007

Complete resolution of steroid-resistant organizing pneumonia associated with myelodysplastic syndrome following allogeneic hematopoietic cell transplantation. 査読国際誌

Takeru Asano, Nobuharu Fujii, Daigo Niiya, Hisakazu Nishimori, Keiko Fujii, Ken-Ichi Matsuoka, Koichi Ichimura, Toshihisa Hamada, Eisei Kondo, Yoshinobu Maeda, Yasushi Tanimoto, Katsuji Shinagawa, Mitsune Tanimoto

SpringerPlus 3 3 - 3 2014年

記述言語：英語掲載種別：研究論文（学術雑誌）

Pulmonary complications in patients with hematological malignancies are often caused by infection but are sometimes associated with an underlying disease such as organizing pneumonia (OP). Here, we report a case of life-threatening steroid-resistant OP associated with myelodysplastic syndrome (MDS) and successfully performed allogeneic hematopoietic cell transplantation (HSCT). A 33-year-old female with refractory anemia with excess blasts-1 that had progressed from refractory anemia with ringed sideroblasts and concomitant Sweet's syndrome was admitted. Multiple pulmonary infiltrates were revealed on a chest computed tomography scan, which progressively worsened even after chemotherapy and corticosteroid therapy. No evidence of infection was observed in bronchoalveolar lavage fluid. A histological examination of a transbronchial lung biopsy specimen showed lymphocyte invasion with fibrosis, indicating that the pulmonary infiltrates were OP associated with MDS. Before transplantation, she suffered from respiratory failure and required oxygen supplementation. She developed idiopathic pneumonitis syndrome on day 61 that responded well to corticosteroid therapy, and the OP pulmonary infiltrates improved gradually after HSCT, She was discharged on day 104 and is well without recurrence of OP or MDS 2 years after HSCT.

DOI： 10.1186/2193-1801-3-3

肺移植における血液製剤準備量と使用量査読

浅野尚美, 池田亮, 小郷博昭, 藤井敬子, 杉山暖子, 池田和真, 小出典男

日本輸血細胞治療学会誌 = Japanese journal of transfusion and cell therapy 56 ( 5 ) 606 - 611 2010年10月

記述言語：日本語出版者・発行元：The Japan Society of Transfusion Medicine and Cell Therapy

岡山大学病院では，1998年に本邦初の生体肺移植が行われて以降2009年3月までに52例の生体肺移植と15例の脳死肺移植の計67例の肺移植が行われた．特に脳死肺移植では，限られた時間内に血液製剤を準備する必要があり，これまでの肺移植における血液製剤使用量から術前準備量について検討を行った．<br> 赤血球製剤の平均準備量は57.4U，平均使用量は33.5U，C/T比（交差試験単位数/輸血血液単位数）1.73であった．FFPの平均準備量は43.3U，平均使用量は19.4Uで，PCの平均準備量は27.7U，平均使用量は19.8Uであった．両肺移植の平均血液使用量が，赤血球製剤37.9U，FFP 21.8U，PC 22.8Uであったのに対し，片肺移植の平均血液使用量は，赤血球製剤11.5U，FFP 7.0U，PC 4.5Uで有意差が認められた．また，赤血球製剤を100U以上準備した症例が5例あり，全て両肺移植で，うち3例が脳死移植であった．<br> 肺移植では，症例毎の癒着の程度の相違等で一律の血液準備量の決定は難しいと考えられるが，今回の肺移植における血液製剤使用量の検討から血液の必要量については，両肺移植か片肺移植であるか，恐らく，人工心肺の使用の有無が大きな因子であることが示唆された．また，緊急の脳死肺移植や大量の血液製剤準備に対応できるよう，日常的に異型適合血の選択を含めた緊急時の対応と診療科等との連携を深めることが必要であると考えられた．<br>

DOI： 10.3925/jjtc.56.606

その他リンク： http://search.jamas.or.jp/link/ui/2011048595

Plasma stromal cell-derived factor-1 during granulocyte colony-stimulating factor-induced peripheral blood stem cell mobilization 査読

T. Kozuka, F. Ishimaru, K. Fujii, K. Masuda, K. Kaneda, T. Imai, N. Fujii, H. Ishikura, S. Hongo, T. Watanabe, K. Shinagawa, K. Ikeda, K. Niiya, M. Harada, M. Tanimoto

Bone Marrow Transplantation 31 ( 8 ) 651 - 654 2003年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

In this report, we examined plasma stromal cell-derived factor-1 levels in normal healthy donors for allogeneic peripheral blood stem cell transplantation (PBSCT) and in patients for autologous PBSCT using an enzyme-linked immunosorbent assay. The average level of plasma stromal cell-derived factor-1 was 2197pg/ml before granulocyte colony-stimulating factor administration and 1899 pg/ml on day 4, demonstrating a significant decrease in the peripheral blood of healthy donors (P = 0.0003). In patients for autologous PBSCT, a significant decrease of plasma stromal cell-derived factor-1 in the peripheral blood was also observed (P = 0.0464). However, the physiologic gradient of stromal cell-derived factor-1 between peripheral blood and bone marrow was never inverted in normal healthy donors or in autologous PBSCT patients. Our results suggest that stromal cell-derived factor-1 may not be involved in the granulocyte colony-stimulating factor-induced release of CD34+ cells to the peripheral blood. Further studies of a possible additive effect of granulocyte colony-stimulating factor and stromal cell-derived factor-1 are warranted.

DOI： 10.1038/sj.bmt.1703901

Risk of Neutropenic Fever and Early Infectious Complications after Autologous Peripheral Blood Stem Cell Transplantation for Malignant Diseases 査読国際誌

FUJII Keiko, AOYAMA Masako, SHINAGAWA Katsuji, MATSUO Keitaro, TAKENAKA Katsuto, IKEDA Kazuma, KOJIMA Kensuke, ISHIMARU Fumihiko, KIURA Katsuyuki, UEOKA Hiroshi, NIIYA Kenji, TANIMOTO Mitsune, HARADA Mine

International journal of hematology 76 ( 2 ) 186 - 191 2002年8月

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