血液疾患研究所

血液疾患研究所の概要

　神鋼病院の研究部門として2011年1月1日に開設されました。外来Eブロック内に、検査室（細胞治療室）とセルプロセッシングが可能な部屋、計2室を造設しました。検査室では、倒立顕微鏡1台、実体顕微鏡1台、Real time PCR装置2台（現在は総合医学研究センターで使用）、自動核酸抽出装置２台、吸光光度計１台、フローサイトメトリー（FACSCant II）1台、生物試料保存液体窒素容器2台、-30℃冷凍庫1台、4℃冷蔵庫２台、無菌接合機１台、CO2インキュベータの設備を有しています。

セルプロセッシング室は部屋全体がNASA Class 100,000の陽圧無菌ルームであり、その中にClass IIAの安全キャビネットを設置し、内の清浄度はClass100を保つような設計で、2011年8月より稼働しています。この細胞治療室と神鋼記念病院 血液内科が共に血液疾患研究所の活動をしています。

研究者

有馬 靖佳 研究所 血液病センター長 / 無菌治療室長 / 血液内科 部長・特任副院長
常峰 紘子 研究所 細胞治療室長 / 血液内科 科長・特任部長
田中 康博 研究所 研究員 / 血液内科 医長
青山 有美 研究所 研究員　兼 ⾎液内科 医長
中村 直和 非常勤
生成 涼 研究所 研究員 / 血液内科 専攻医
武 修作 研究所 研究員　兼 ⾎液内科 専攻医
柱本　まどか 研究所 研究員　兼 ⾎液内科 専攻医
松本 真弓 研究所 移植医療支援室副室長 / 移植コーディネーター
佐々木 美穂 研究所 研究員
厨子 佑里子 研究所 研究員
斎藤 敏晴 研究所 研究員
高橋 隆幸 非常勤

血液疾患研究所 所長

血液疾患研究所 所長
有馬 靖佳

神鋼記念病院血液病センター長。
神戸大学を昭和61年に卒業。日本内科学会認定内科医・指導医、日本内科学会総合内科専門医、京都大学医学部臨床教授、日本医師会認定産業医、日本血液学会専門医・指導医・代議員、日本造血幹細胞移植学会認定医・代議員、日本臨床腫瘍学会　暫定指導医、日本エイズ学会認定医などの資格を持つ。

実施中の臨床研究/ 臨床試験とその概要

　腫瘍細胞と細胞障害性T細胞の間を直接架橋して腫瘍の撲滅をはかる免疫治療には、CAR-T療法と二重特異性抗体があります。神鋼記念病院では、急性リンパ性白血病の患者様4名にブリナツマブという二重特異性抗体治療を施行して来ました。2023年度以降は、B細胞性非ホジキンリンパ腫に対しエプコリタマブ(エプキンリ○R)、骨髄腫に対してエルラナタマブ(エルレフィオ○R)という新規発売になった二重特異性抗体の治療を行っています。2024年度に血縁者末梢血幹細胞移植を行った患者様はおふたりとも、移植後シクロフォスファミドというGVHD予防を用いた方法で、順調な経過をたどっておられます。この移植方法では、患者とドナー間のHLAが半分だけ一致でも移植可能なので、たとえば親子間ならばドナーに健康状態などの問題がなければほぼ100％移植が可能になります。今後とも適応がある患者さんには、どんどん推奨させて頂けそうです。とはいえ移植後GVHDが起こって、コントロールが困難な場合があります。当院ではすでに急性GVHDに対する間葉系幹細胞療法を行っておりましたが、昨年度からは慢性GVHDに対するECP治療も開始しています。

研究業績

1．当院が主たる研究者であるもの

  • Nakamura N, Arima N, Takakuwa T, Yoshioka S, Imada K, Fukushima K, Hotta M, Fuchida SI, Kanda J, Uoshima N, Shimura Y, Tanaka H, Ohta K, Kosugi S, Yagi H, Yoshihara S, Yamamura R, Adachi Y, Hanamoto H, Shibayama H, Hosen N, Ito T, Shimazaki C, Takaori-Kondo A, Kuroda J, Matsumura I, Hino M; Kansai Myeloma Forum. Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study. Ann Hematol. 2024 Mar 16. doi: 10.1007/s00277-024-05705-z. Online ahead of print. PMID: 38492020
  • Nakamura N, Yamamoto N, Kondo T, Matsumoto M, Ikunari R, Sakai T, Tanaka Y, Tsunemine H, Takeda J, Kanda J, Nannya Y, Ogawa S, Takaori-Kondo A, Arima N. Sustained remission after cord blood transplantation for breast cancer with lung metastases and myelodysplastic syndrome. Int J Hematol. 2024 Jun;119(6):762-767.
  • Nakamura N, Ikunari R, Tanaka Y, Tsunemine H, Takeda J, Arima N. Pathogenic TNFRSF13B Variant in an Adult Japanese Patient with Common Variable Immunodeficiency. Intern Med. 2024 Jul 11. doi: 10.2169/internalmedicine.4057-24.
  • Nakamura N, Tsunemine H, Ikunari R, Sakai T, Arima N. COVID-19 antibody titers after tixagevimab-cilgavimab injection in patients with hematologic diseases; a single-center, prospective study. Leuk Lymphoma. 2024 Aug;65(8):1117-1126.
  • Numata J, Tsunemine H, Imai A, Nakamura N, Sakai T, Itoh T, Arima N. Recurrence of solitary plasmacytoma in the liver 10 years after the onset of multiple bone lesions. J Clin Exp Hematop. 2024;64(1):65-70.
  • Tanaka Y, Sakai T, Tsunemine H, Ito T, Arima N. Successful treatment of isolated central nervous system recurrence of primary testicular lymphoma by autologous stem cell transplantation using a conditioning regimen of thiotepa and busulfan. J Clin Exp Hematop. 2024 Feb 28. doi: 10.3960/jslrt.23039.
  • 松本真弓、岡耕平. 学会認定・臨床輸血看護師の専門的実践内容に関する実態調査. 日本輸血細胞治療学会誌. 70(6):641-647, 2024.
  • 武修作, 田中康博, 柱本まどか, 常峰紘子, 有馬靖佳. Picture in Clinical Hematology No.167臨床血液　2024 年 65 巻 11 号 p. 1351
  • Nakamura N, Tsunemine H, Sakai T, Arima N. Biomarkers for predicting response to corticosteroid therapy for immune thrombocytopenic purpura. Br J Haematol., 2023 May;201(4):774-782
  • Nakamura N, Jo T, Arai Y, Matsumoto M, Sakai T, Tsunemine H, Takaori-Kondo A, Arima N. Benefits of plerixafor for mobilization of peripheral blood stem cells prior to autologous transplantation: a dual-center retrospective cohort study. Cytotherapy, 2023 Jul;25(7):773-781
  • Tsunemine H, Sasaki M, Zushi Y, Saitoh T, Shimizu N, Tomaru Y, Aoyama Y, Yamamoto R, Sakai T, Arima N, Kodaka T, Takahashi T. Feasibility of the routine clinical use of a multiplex virus polymerase chain reaction assay based on blood virus detection in hematopoietic stem cell-transplanted patients. Int J Clin Med. 13: 67-81. 2022
  • Imashuku S, Tsunemine H, Shimazaki C. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography delineates involved sites in the cervical spine in Langerhans cell histiocytosis. EJHaem 24;3(3):1042-1043. 2022
  • Arima N. Dual effects of natural killer cells in transplantation for leukemia. Crit Rev Oncol Hematol. 158:103206, 2021.
  • Arima N, Kanda J, Yabe T, Morishima Y, Tanaka J, Kako S, Sakaguchi H, Kato M, Ohashi K, Ozawa Y, Fukuda T, Ota S, Tachibana T, Onizuka M, Ichinohe T, Atsuta Y, Kanda Y. Increased Relapse Risk of Acute Lymphoid Leukemia in Homozygous HLA-C1 Patients after HLA-Matched Allogeneic Transplantation: A Japanese National Registry Study. Biol Blood Marrow Transplant. 2020 Mar;26(3):431-437.
  • Nobuyoshi Arima, Junya Kanda, Toshio Yabe, Yasuo Morishima, Junji Tanaka, Shinichi Kako, Hirotoshi Sakaguchi, Motohiro Kato, Kazuteru Ohashi, Yukiyasu Ozawa, Takahiro Fukuda, Shuichi Ota, Takayoshi Tachibana, Makoto Onizuka, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshinobu Kanda: Increased Relapse Risk of Acute Lymphoid Leukemia in Homozygous HLA-C1 Patients after HLA-Matched Allogeneic Transplantation: A Japanese National Registry Study. Biol Blood Marrow Transplant. 2020, 26: 431-437
  • 松本真弓、有馬靖佳、松浦秀哲、西岡純子、谷口容、山崎喜子、村田真由美、山野靖子、細野晃、奥田誠、阿部真、河野武弘、紀野修一、面川進、竹下明裕、室井一男、牧野茂義：輸血開始後の患者観察に関する実態調査に学ぶ輸血看護の課題. 日本輸血細胞治療学会誌, 66(6);735-742,2020.
  • Yuriko Zushi, Miho Sasaki, Toshiharu Saitoh, Yumi Aoyama, Yuta Gotoh, Hiroko Tsunemine, Taiichi Kodaka, Atsuo Okamura, Takayuki Takahashi: Gamma-heavy chain monoclonal gammopathy with undetermined significance (MGUS). J Clin Exp Hematopathol 2019; 59: 119-123.
  • Satoko Hijii, Taiichi Kodaka, Takae Goka, Yumi Aoyama, Hiroko Tsunemine, Takayuki Takahashi: Acquired von Willebrand syndrome secondary to Waldenström’s Macroglobulinemia. Intern Med 2019, DOI: 10.5430/crim.v6n3p13.
  • Yuta Gotoh, Yumi Aoyama, Hiroko Tsunemine, Yuka Idei, Ayano Mori, Taiichi Kodaka, Sachiko Iba, Akihiro Tomita, Tomoo Itoh, Takayuki Takahashi: IgA-producing lymphoplasmacytic lymphoma carrying chromosomal abnormality of t(8;14). J Clin Exp Hematop　2019; 59: 124-129.
  • Naoya Kuwahara, Taiichi Kodaka, Yuriko Zushi, Miho Sasaki, Takae Goka, Hayato Maruoka, Yumi Aoyama, Hiroko Tsunemine, Taku Yamane, Jun Kobayashi, Toru Kawakami, Fumihiro Ishida, Takayuki Takahashi: T-cell large granular lymphocytic (LGL) leukemia consists of CD4+/CD8dim and CD4-/CD8+ LGL populations in association with immune thrombocytopenia, autoimmune neutropenia, and monoclonal B-cell lymphocytosis. J Clin Exp Hematop 2019, 59 (4), 202-206
  • Hiroko Tsunemine, Yuriko Zushi, Miho Sasaki, Yuko Nishikawa, Akiyo Tamura, Yumi Aoyama, Taiichi Kodaka, Tomoo Itoh, Takayuki Takahashi: Gamma heavy chain disease (γ-HCD) as iatrogenic immunodeficiency- associated lymphoproliferative disorder: possible emergent subtype of rheumatoid arthritis-associated -HCD. J Clin Exp Hematopathol 2019, 59 (4), 196-201
  • Yumi Aoyama, Sakai K, Kodaka T, Tsunemine H, Nishio K, Itoh T, Inoue D, Takahashi T: Myelodysplastic/myeloproliferative neosplasm with ring sideroblasts and thromboctyosis (MDS/MPN with RS-T) complicated by hyperleukocytosis and gene analysis in relation to leukocytosis. J Clin Exp Hematopathol 2018, 59: 29-33.
  • Yuta Gotoh, Hiroko Tsunemine, Yuriko Zushi, Yumi Aoyama, Taiichi Kodaka, Tomoo Itoh, Takayuki Takahashi. Successful allogeneic hematopoietic stem cell transplantation for aleukemic Philadelphia chromosome-positive acute lymphoblastc leukemia secondary to chemo-radiotherapy for breast cancer: Journal of Hematopoietic Cell Transplantation, 7:152-156, 2018.
  • Yumi Aoyama, Hiroko Tsunemine, Yuriko Zushi, Hayato Maruoka, Yuta Goto, Taiichi Kodaka, Tomoo Itoh, Takayuki Takahashi. Colonal monomorphic epitheliotropic intestinal T-cell lymphoma with novel phenotype of cytoplasmic CD3 expression: J Clin Exp Hematopathol, 58:102-106, 2018.
  • Shogo Nishino, Taiichi Kodaka, Yoshie Sawada, Takae Goka, Yuta Gotoh, Hiroko Tsunemine, Takayuki Takahashi. Marked rebound thrombocytosis in response to glucocorticoid in a patient with acquired amegakaryocytic thrombocytopenia: J Clin Exp Hematopathol, 58:166-170, 2018.

2．多施設共同研究など

  • Morita-Fujita M, Shindo T, Iemura T, Arai Y, Kanda J, Okada K, Ueda Y, Yoshiyuki O, Anzai N, Mori T, Ishikawa T, Otsuka Y, Yonezawa A, Yuhi N, Imada K, Oba A, Itoh M, Okamoto Y, Kitano T, Ikeda T, Kotani S, Akasaka T, Yago K, Watanabe M, Nohgawa M, Tsuji M, Takeoka T, Yamamoto R, Arima N, Yoshinaga N, Hishizawa M, Yamashita K, Kondo T, Takaori-Kondo A; Kyoto Stem Cell Transplantation Group (KSCTG). Epitope mismatch at HLA-DRB1 associates with reduced relapse risk in cord blood transplant for standard-risk hematological malignancy.Transplant Cell Ther. doi: 10.1016/j.jtct.2023.03.002, 2023
  • Miyazaki K, Sakai R, Iwaki N, Yamamoto G, Murayama K, Nishikori M, Sunami K, Yoshida I, Yano H, Takahashi N, Okamoto A, Munemoto S, Sawazaki A, Suehiro Y, Fukuhara N, Wake A, Arai A, Masaki Y, Toyama K, Yokoyama A, Tsunemine H, Hasegawa Y, Matsumoto K, Yamada T, Nishimura Y, Tamaru S, Asano N, Miyawaki K, Izutsu K, Kinoshita T, Suzuki R, Ohshima K, Kato K, Katayama N, Yamaguchi M. Five-year follow-up of a phase II study of DA-EPOCH-R with high-dose MTX in CD5-positive DLBCL. Cancer Sci. doi: 10.1111/cas.15784. 2023
  • Iemura T, Arai Y, Kitawaki T, Kanda J, Kondo T, Ueda Y, Mori T, Imada K, Yonezawa A, Yago K, Anzai N, Kotani S, Nohgawa M, Kitano T, Itoh M, Arima N, Moriguchi T, Watanabe M, Tsuji M, Yamashita K, Takaori-Kondo A; Kyoto Stem Cell Transplantation Group (KSCTG). Coexistence of HLA and KIR ligand mismatches as a risk factor for viral infection early after cord blood transplantation. Bone Marrow Transplant;57(5):781-789.2022
  • Muranushi H, Kanda J, Kobayashi M, Maeda T, Kitano T, Tsuji M, Ueda Y, Ishikawa T, Nohgawa M, Watanabe M, Imada K, Moriguchi T, Itoh M, Ohno H, Yonezawa A, Hirata H, Arima N, Asagoe K, Anzai N, Nagata K, Yasuno S, Kuwabara Y, Kitao H, Kim I, Kawagishi K, Ueshima K, Tominari S, Nakayama T, Yamashita K, Takaori-Kondo A. Bortezomib-cyclophosphamide-dexamethasone induction/consolidation and bortezomib maintenance for transplant-eligible newly diagnosed multiple myeloma: phase 2 multicenter trial. Hematology. 27(1):239-248.2022
  • Wada F, Kanda J, Yoshioka S, Ishikawa T, Akasaka T, Ueda Y, Hirata H, Arai Y, Yago K, Anzai N, Watanabe M, Ikeda T, Yonezawa A, Imada K, Itoh M, Kitano T, Takeoka T, Hishizawa M, Nohgawa M, Arima N, Asagoe K, Kondo T, Takaori-Kondo A; Kyoto Stem Cell Transplantation Group (KSCTG). Single Cord Blood Transplantation Versus HLA-Haploidentical-related Donor Transplantation Using Posttransplant Cyclophosphamide in Patients With Hematological Malignancies. Transplantation. 106(6):1279-1287.2022
  • Iwasaki M, Kanda J, Arai Y, Kondo T, Ishikawa T, Ueda Y, Imada K, Akasaka T, Yonezawa A, Yago K, Nohgawa M, Anzai N, Moriguchi T, Kitano T, Itoh M, Arima N, Takeoka T, Watanabe M, Hirata H, Asagoe K, Miyatsuka I, An LM, Miyanishi M, Takaori-Kondo A. Establishment of a predictive model for GVHD-free, relapse-free survival after allogeneic HSCT using ensemble learning. Blood Adv. 6(8):2618-2627.2022
  • Morishima S, Fukuda T, Doki N, Mori T, Onizuka M, Kawakita T, Kato C, Ozawa Y, Tanaka M, Kurokawa M, Kamimura T, Inoue M, Tanaka J, Arima N,…., Ichinohe T, Atsuta Y, Morishima Y; HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation. Individual HLAs influence immunological events in allogeneic stem cell transplantation from HLA-identical sibling donors. Bone Marrow Transplant. 56(3):646-654, 2021.
  • Kanaya M, Morishima Y, Arima N, Hirayama M, Shiratori S, Doki N, Ozawa Y, Fukuda T, Tanaka M, Sawa M, Takada S, and Morishima S. HLA-B Leader Dimorphism Impacts on Outcomes of HLA-Matched Related/Unrelated Transplantation: Analysis of the Japanese Society for Transplantation and Cellular Therapy. Blood, 138, 2919, 2021.
  • Nguyen MAT, Hosokawa K, Yoroidaka T, Maruyama H, Espinoza JL, Elbadry MI, Mohiuddin M, Tanabe M, Katagiri T, Nakagawa N, Chonabayashi K, Yoshida Y, Arima N, Kashiwase K, Saji H, Ogawa S, Nakao S. Resistance of KIR Ligand-Missing Leukocytes to NK Cells In Vivo in Patients with Acquired Aplastic Anemia. Immunohorizons. 2020 Jul 17;4(7):430-441.
  • Matsui H, Arai Y, Imoto H, Mitsuyoshi T, Tamura N, Kondo T, Kanda J, Ishikawa T, Imada K, Ueda Y, Toda Y, Anzai N, Yago K, Nohgawa M, Yonezawa A, Tsunemine H, Itoh M, Yamamoto K, Tsuji M, Moriguchi T, Takaori-Kondo A; Kyoto Stem Cell Transplantation Group (KSCTG). Risk factors and appropriate therapeutic strategies for thrombotic microangiopathy after allogeneic HSCT. Blood Adv. 2020 Jul 14;4(13):3169-3179.
  • Watanabe M, Kanda J, Arai Y, Hishizawa M, Nishikori M, Ishikawa T, Imada K, Ueda Y, Akasaka T, Yonezawa A, Nohgawa M, Kitano T, Itoh M, Takeoka T, Moriguchi T, Yago K, Arima N, Anzai N, Watanabe M, Kondo T, Takaori-Kondo A; Kyoto Stem Cell Transplantation Group (KSCTG). Impact of Donor Source on Allogeneic Hematopoietic Stem Cell Transplantation for Mature T Cell and Natural Killer Cell Neoplasms in the Kyoto Stem Cell Transplantation Group. Biol Blood Marrow Transplant. 2020 Dec;26(12):2346-2358.
  • Yasuo Morishima, Satoko Morishima, Makoto Murata, Nobuyoshi Arima, Naoyuki Uchida, Yasuhiro Sugio, Satoshi Takahashi, Yoshiko Matsuhashi, Makoto Onizuka, Tetsuya Eto, Koji Nagafuji, Yasushi Onishi, Masami Inoue, Yoshiko Atsuta, Takahiro Fukuda Tatsuo Ichinohe, Shunichi Kato. Junya Kanda: Impact of Homozygous Conserved Extended HLA Haplotype on Single Cord Blood Transplantation: Lessons for Induced Pluripotent Stem Cell Banking and Transplantation in Allogeneic Settings. Biol Blood Marrow Transplant. 2020, 26: 132-138
  • Junya Kanda, Yasuyuki Arai, Tadakazu Kondo, Takayuki Ishikawa, Yasunori Ueda, Kazunori Imada, Takashi Akasaka, Akihito Yonezawa, Kazuhiro Yago, Masaharu Nohgawa, Naoyuki Anzai, Toshinori Moriguchi, Toshiyuki Kitano, Mitsuru Itoh, Nobuyoshi Arima, Tomoharu Takeoka, Mitsumasa Watanabe, Hirokazu Hirata, Kosuke Asagoe, Masanori Miyanishi, Isao Miyatsuka, Le My An, Akifumi Takaori-Kondo, “Establishment of a Predictive Model of GvHD-Free, Relapse-Free Survival after Allogeneic Hematopoietic Stem Cell Transplantation Using a Machine Learning Algorithm.” Blood. 2019, 134 (Supplement_1): 3337.
  • Hiroshi Kawabata, Kensuke Usuki, Maki Shindo-Ueda, Junya Kanda, Kaoru Tohyama, Akira Matsuda, Kayano Araseki, Tomoko Hata, Takahiro Suzuki, Hidekazu Kayano, Kei Shimbo, Shigeru Chiba, Takayuki Ishikawa, Nobuyoshi Arima, Masaharu Nohgawa, Yasushi Miyazaki, Mineo Kurokawa, Shunya Arai, Kinuko Mitani, Akifumi Takaori-Kondo & the Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes: Serum ferritin levels at diagnosis predict prognosis in patients with low blast count myelodysplastic syndromes. Int J Hematol. 2019, 110(5):533-542.
  • Okada M, Imagawa J, Tanaka H, Nakamae H, Hino M, Murai K, Ishida Y, Kumagai T, Sato S, Ohashi K, Sakamaki H, Wakita H, Uoshima N, Nakagawa Y, Minami Y, Ogasawara M, Takeoka T, Akasaka H, Utsumi T, Uike N, Sato T, Ando S, Usuki K, Mizuta S, Hashino S, Nomura T, Shikami M, Fukutani H, Ohe Y, Kosugi H, Shibayama H, Maeda Y, Fukushima T, Yamazaki H, Tsubaki K, Kukita T, Adachi Y, Nataduka T, Sakoda H, Yokoyama H, Okamoto T, Shirasugi Y, Onishi Y, Nohgawa M, Yoshihara S, Morita S, Sakamoto J, Kimura S; DADI Trial Group, Japan. Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment. Clin Lymphoma Myeloma Leuk, 18:353-360, 2018.
  • Umeda K, kato I, Kawaguchi K, Tasaka K, Kamitori T, Ogata H, Mikami T, Hiramatsu H, Saito R, Ogawa O, Takahashi T, Adachi S: High incidence of BK virus-associated hemorrhagic cystitis in children after second or third allogeneic hematopoietic stem cell transplantation. Pediatric Transplantation, Apr 14: e13183. Doi:10.1111/petr.13183 2018.
  • Nakaya A, Yagi H, Kaneko H, Kosugi S, Kida T, Adachi Y, Shibayama H, Kohara T, Kamitsuji Y, Fuchida SI, Uoshima N, Kawata E, Uchiyama H, Shimura Y, Takahashi T, Urase F, Ohta K, Hamada T, Miyamoto K, Kobayashi M, Shindo M, Tanaka H, Shimazaki C, Hino M, Kuroda J, Kanakura Y, Takaoari-Kondo A, Nomura S, Matsumura I; Kansai Myeloma Forum Investigators. Retrospective analysis of primary plasma cell leukemia in Kansai Myeloma Forum registry. Leuk Res Rep. 2018 Jul 4;10:7-10. doi: 10.1016/j.lrr.2018.07.001.
  • Kono M, Saigo K, Matsuhiroya S, Takahashi T, Hashimoto M, Obuchi A, Imoto S, Nishiyama T, Kawano S. Detection of activated neutrophils by reactive oxygen species production using a hematology analyzer. J Immunol Methods, 463:122-126, 2018.

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