Updated on 2021/10/20

写真a

 
MURATA, Makoto
 
Organization
Graduate School of Medicine Program in Integrated Medicine Internal Medicine Associate professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Associate professor
Contact information
メールアドレス

Degree 1

  1. 医学博士 ( 2003.6   名古屋大学 ) 

Research Interests 3

  1. 造血細胞移植

  2. 移植免疫学

  3. 血液内科学

Research Areas 2

  1. Others / Others  / Hematology

  2. Life Science / Hematology and medical oncology

Current Research Project and SDGs 1

  1. 血液内科学

Research History 11

  1. 名古屋大学大学院医学系研究科   血液・腫瘍内科学   准教授

    2016.4

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    Country:Japan

  2. 名古屋大学医学部附属病院   血液内科   講師

    2009.5 - 2016.3

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    Country:Japan

  3. 名古屋大学医学部附属病院   血液内科   助教

    2007.4 - 2009.4

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    Country:Japan

  4. 名古屋大学医学部附属病院   血液内科   助手

    2005.4 - 2007.3

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    Country:Japan

  5. 名古屋大学医学部附属病院   血液内科   医員

    2004.4 - 2005.3

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    Country:Japan

  6. 名古屋大学医学部附属病院   難治感染症部   医員

    2003.4 - 2004.3

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    Country:Japan

  7. Fred Hutchinson Cancer Research Center   Immunology Program   Postdoctoral Fellow

    2000.3 - 2003.3

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    Country:United States

  8. 名古屋大学大学院医学系研究科   分子細胞内科学   大学院生

    1999.4 - 2003.6

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    Country:Japan

  9. 名古屋大学医学部   第一内科   研究生

    1998.8 - 1999.3

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    Country:Japan

  10. 名古屋第一赤十字病院   血液内科   医員

    1994.4 - 1998.7

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    Country:Japan

  11. 名古屋第一赤十字病院・臨床研修

    1992.4 - 1994.3

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    Country:Japan

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Education 2

  1. Nagoya University   Graduate School, Division of Medical Sciences

    1999 - 2003

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    Country: Japan

  2. Nagoya University   Faculty of Medicine

    1986 - 1992

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    Country: Japan

Professional Memberships 10

  1. 日本血液学会   専門医、指導医、代議員

  2. 日本造血細胞移植学会   造血細胞移植認定医、評議員、監事

  3. 日本輸血・細胞治療学会   認定医、細胞治療認定管理師、評議員

  4. 日本内科学会   認定内科医、指導医

  5. 日本血液疾患免疫療法学会   理事

  6. 日本組織適合性学会   評議員

  7. 日本癌学会

  8. 日本臨床腫瘍学会

  9. 日本再生医療学会

  10. American Society of Hematology   International Member

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Awards 4

  1. 日本再生医療学会総会優秀演題賞

    2017.3   日本再生医療学会  

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  2. EBMT Best Science Poster Award

    2012.4   European Group for Blood and Marrow Transplantation  

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    Country:Switzerland

  3. 日本臨床血液学会奨励賞

    2003.8   日本臨床血液学会  

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    Country:Japan

  4. 日本臨床血液学会奨励賞

    2004.9   日本臨床血液学会  

    村田 誠

 

Papers 216

  1. Prophylactic and therapeutic treatment of graft-versus-host disease in Japan Invited Reviewed

    Murata M

    Int J Hematol   Vol. 101 ( 5 ) page: 467-86   2015

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  2. Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection Reviewed

    Hanajiri R, Murata M, Sugimoto K, Murase M, Sakemura R, Goto T, Watanabe K, Imahashi N, Terakura S, Ohashi H, Akatsuka Y, Kurahashi S, Miyamura K, Kiyoi H, Nishida T, Naoe T

    Bone Marrow Transplant   Vol. 50 ( 9 ) page: 1187-94   2015

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

  3. Target antigen density governs the efficacy of anti-CD20-CD28-CD3ζ chimeric antigen receptor-modified effector CD8+ T cells Reviewed

    Watanabe K, Terakura S, Martens AC, van Meerten T, Uchiyama S, Imai M, Sakemura R, Goto T, Hanajiri R, Imahashi N, Shimada K, Tomita A, Kiyoi H, Nishida T, Naoe T, Murata M

    J Immunol   Vol. 194 ( 3 ) page: 911-20   2015

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

  4. Chimerism status after unrelated donor bone marrow transplantation with fludarabine-melphalan conditioning is affected by the melphalan dose and is predictive of relapse Reviewed

    Imahashi N, Ohashi H, Terakura S, Miyao K, Sakemura R, Kato T, Sawa M, Yokohata E, Kurahashi S, Ozawa Y, Nishida T, Kiyoi H, Watamoto K, Kohno A, Kasai M, Kato C, Iida H, Naoe T, Miyamura K, Murata M

    Ann Hematol   Vol. 94 ( 7 ) page: 1139-48   2015

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

  5. Age influences post-graft-versus-host disease non-relapse mortality in adults with acute graft-versus-host disease of varying severity following allogeneic hematopoietic cell transplant Reviewed

    Nakane T, Fukuda T, Kanda J, Taniguchi S, Eto T, Ohashi K, Nakamae H, Kurokawa M, Mori T, Morishima Y, Nagamura-Inoue T, Sakamaki H, Atsuta Y, Murata M

    Leuk Lymphoma     page: 1-6   2015

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

  6. Biological significance of HLA locus matching in unrelated donor bone marrow transplantation Reviewed

    Morishima Y, Kashiwase K, Matsuo K, Azuma F, Morishima S, Onizuka M, Yabe T, Murata M, Doki N, Eto T, Mori T, Miyamura K, Sao H, Ichinohe T, Saji H, Kato S, Atsuta Y, Kawa K, Kodera Y, Sasazuki T

    Blood   Vol. 125 ( 7 ) page: 1189-97   2015

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

  7. Impact of conditioning intensity and TBI on acute GVHD after hematopoietic cell transplantation Reviewed

    Nakasone H, Fukuda T, Kanda J, Mori T, Yano S, Kobayashi T, Miyamura K, Eto T, Kanamori H, Iwato K, Uchida N, Mori S, Nagamura T, Ichinohe T, Atsuta Y, Teshima T, Murata M

    Bone Marrow Transplant   Vol. 50 ( 4 ) page: 559-65   2015

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

  8. Simple and efficient generation of virus-specific T cells for adoptive therapy using anti-4-1BB antibody Reviewed

    Imahashi N, Nishida T, Goto T, Terakura S, Watanabe K, Hanajiri R, Sakemura R, Imai M, Kiyoi H, Naoe T, Murata M

    J Immunother   Vol. 38 ( 2 ) page: 62-70   2015

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

  9. Treatment of patients with adult T cell leukemia/lymphoma with cord blood transplantation: a Japanese nationwide retrospective survey Reviewed

    Biol Blood Marrow Transplant   Vol. 20   page: 1968-74   2014

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

  10. Comparison of continuous and twice-daily infusions of cyclosporine A for graft-versus-host-disease prophylaxis in pediatric hematopoietic stem cell transplantation. Reviewed International journal

    Katsutsugu Umeda, Souichi Adachi, Shiro Tanaka, Atsushi Ogawa, Naoki Hatakeyama, Kazuko Kudo, Naoki Sakata, Shunji Igarashi, Kumi Ohshima, Nobuyuki Hyakuna, Motoaki Chin, Hiroaki Goto, Yoshiyuki Takahashi, Eiichi Azuma, Katsuyoshi Koh, Akihisa Sawada, Koji Kato, Masami Inoue, Yoshiko Atsuta, Akiyoshi Takami, Makoto Murata

    Pediatric blood & cancer   Vol. 62 ( 2 ) page: 291 - 298   2015.2

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

    BACKGROUND: Cyclosporine A (CsA) is used widely for graft-versus-host disease (GVHD) prophylaxis in hematopoietic stem cell transplantation (HSCT); however, the optimal schedule of its administration has not been established. Although comparative studies of adult patients undergoing HSCT have demonstrated enhanced efficacy and safety of twice-daily infusion (TD) compared with continuous infusion (CIF) of CsA, to our knowledge, similar studies have not yet been performed in pediatric groups. PROCEDURE: A self-administered questionnaire was used to retrospectively compare the clinical outcome and incidence of CsA-associated adverse events of 70 pediatric acute myelogenous leukemia patients who were receiving CsA by TD (n = 36) or CIF (n = 34) as GVHD prophylaxis for their first allogeneic HSCT. RESULTS: The cumulative incidences of grade II-IV acute GVHD and chronic GVHD, as well as the overall survival and event-free survival rates, did not differ significantly between the TD and CIF groups; however, the incidence of severe hypertension was significantly higher in the CIF group than the TD group. CONCLUSIONS: The analysis presented here indicates that TD and CIF administration of CsA have similar prophylactic effect on pediatric GVHD and suggest that TD is associated with a lower rate of toxicity than CIF in pediatric patients undergoing HSCT. Pediatr Blood Cancer 2015;62:291-298. © 2014 Wiley Periodicals, Inc.

    DOI: 10.1002/pbc.25243

    PubMed

  11. Mycophenolate mofetil use after unrelated hematopoietic stem cell transplantation for prophylaxis and treatment of graft-versus-host disease in adult patients in Japan Reviewed

    Iida M, Fukuda T, Uchida N, Murata M, Aotsuka N, Minagawa K, Ohashi K, Fukushima K, Kondo T, Eto T, Miyamoto T, Morishima Y, Nagamura T, Atsuta Y, Suzuki R

    Clinical Transplantation   Vol. 28 ( 9 ) page: 980-989   2014

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

  12. Correlations of programmed death 1 expression and serum IL-6 level with exhaustion of cytomegalovirus-specific T cells after allogeneic hematopoietic stem cell transplantation Reviewed

    Kato T, Nishida T, Ito Y, Murase M, Murata M, Naoe T

    Cell Immunol   Vol. 288 ( 1-2 ) page: 53-59   2014

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

  13. Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions Reviewed

    Nishiwaki S, Nakayama T, Murata M, Nishida T, Terakura S, Saito S, Kato T, Mizuno H, Imahashi N, Seto A, Ozawa Y, Miyamura K, Ito M, Takeshita K, Kato H, Toyokuni S, Nagao K, Ueda R, Naoe T

    PLOS one   Vol. 9 ( 5 ) page: e96252   2014

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  14. Successful unrelated cord blood transplantation for adult acquired aplastic anemia using reduced intensity conditioning without ATG Reviewed

    Terakura S, Nishida T, Inamoto Y, Ohashi H, Naoe T, Murata M

    Immunology Letters   Vol. 160 ( 1 ) page: 99-101   2014

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  15. Leukemic evolution of donor-derived cells harboring IDH2 and DNMT3A mutations after allogeneic stem cell transplantation Reviewed

    Yasuda T, Ueno T, Fukumura K, Yamato A, Ando M, Yamaguchi H, Soda M, Kawazu M, Sai E, Yamashita Y, Murata M, Kiyoi H, Naoe T, Mano H

    Leukemia   Vol. 28 ( 2 ) page: 426-428   2014

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  16. Allogeneic transplantation for primary myelofibrosis with bone marrow, peripheral blood, or umbilical cord blood: An analysis of the JSHCT Reviewed

    Murata M, Nishida T, Taniguchi S, Ohashi K, Ogawa H, Fukuda T, Mori T, Kobayashi H, Nakaseko C, Yamagata N, Morishima Y, Nagamura-Inoue T, Sakamaki H, Atsuta Y, Suzuki R, Naoe T

    Bone Marrow Transplant   Vol. 49 ( 3 ) page: 355-360   2014

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  17. Risk factors and organ involvement of chronic graft-versus-host disease in Japan Reviewed

    Kanda J, Nakasone H, Atsuta Y, Toubai T, Yokoyama H, Fukuda T, Taniguchi S, Ohashi K, Ogawa H, Eto T, Miyamura K, Morishima Y, Nagamura-Inoue T, Sakamaki H, Murata M

    Bone Marrow Transplant   Vol. 49 ( 2 ) page: 228-235   2014

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  18. Third-party derived-bone marrow mesenchymal stem cells for steroid-refractory acute graft-versus-host disease: a phase I/II study Reviewed

    Muroi K, Miyamura K, Ohashi K, Murata M, Eto T, Kobayashi N, Taniguchi S, Imamura M, Ando K, Kato S, Mori T, Teshima T, Mori M, Ozawa K

    Int J Hematol   Vol. 98 ( 2 ) page: 206-213   2013

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  19. Identification of a novel HLA-A*24:02-restricted adenovirus serotype 11-specific CD8+ T-cell epitope for adoptive immunotherapy Reviewed

    Imahashi N, Nishida T, Ito Y, Kawada J, Nakazawa Y, Toji S, Suzuki S, Terakura S, Kato T, Murata M, Naoe T

    Molecular Immunology   Vol. 56 ( 4 ) page: 399-405   2013

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  20. Clinical factors predicting the response of acute graft-versus-host disease to corticosteroid therapy: an analysis from the GVHD working group of the Japan Society for Hematopoietic Cell Transplantation Reviewed

    Murata M, Nakasone H, Kanda J, Nakane T, Furukawa T, Fukuda T, Mori T, Taniguchi S, Eto T, Ohashi K, Hino M, Inoue M, Ogawa H, Atsuta Y, Nagamura-Inoue T, Yabe H, Morishima Y, Sakamaki H, Suzuki R

    Biol Blood Marrow Transplant   Vol. 19 ( 8 ) page: 1183-1189   2013

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  21. Efficacy and Long-Term Outcome of Treatment for Pure Red Cell Aplasia following Allogeneic Stem Cell Transplantation from Major ABO-Incompatible Donors Reviewed

    Hirokawa M, Fukuda T, Ohhashi K, Hidaka M, Ichinohe T, Iwato K, Kanamori H, Murata M, Sakura T, Imamura M, Adachi S, Suzuki R, Morishima Y, Sakamaki H

    Biol Blood Marrow Transplant   Vol. 19 ( 7 ) page: 1026-1032   2013

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  22. A case-control study of bronchiolitis obliterans syndrome following allogeneic hematopoietic stem cell transplantation Reviewed

    Nakasone H, Kanda J, Yano S, Atsuta Y, Ago H, Fukuda T, Kakihana K, Adachi T, Yujiri T, Taniguchi S, Taguchi J, Morishima Y, Nagamura T, Sakamaki H, Mori T, Murata M

    Transpl Int   Vol. 26 ( 6 ) page: 631-639   2013

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  23. Impact of hepatitis C virus infection on clinical outcome in recipients after allogeneic hematopoietic cell transplantation Reviewed

    Nakasone H, Kurosawa S, Yakushijin K, Taniguchi S, Murata M, Ikegame K, Kobayashi T, Eto T, Miyamura K, Sakamaki H, Morishima Y, Nagamura T, Suzuki R, Fukuda T

    Am J Hematol   Vol. 88 ( 6 ) page: 477-484   2013

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  24. Escape of Leukemia Blasts from HLA-Specific CTL Pressure in a Recipient of HLA One Locus-Mismatched Bone Marrow Transplantation Reviewed

    Kato T, Terakura S, Murata M, Sugimoto K, Murase M, Iriyama C, Tomita A, Abe A, Suzuki M, Nishida T, Naoe T

    Cellular Immunology   Vol. 276   page: 75-82   2012

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  25. Efficacy and safety of human adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis Reviewed

    Nishiwaki S, Nakayama T, Saito S, Mizuno H, Ozaki T, Takahashi Y, Maruyama S, Nishida T, Murata M, Kojima S, Naoe T

    Int J Hematol   Vol. 96 ( 3 ) page: 295-300   2012

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  26. Phase II study of dose-modified busulfan by real-time targeting in allogeneic hematopoietic stem cell transplantation for myeloid malignancy Reviewed

    Kuwatsuka Y, Kohno A, Terakura S, Saito S, Shimada K, Yasuda T, Inamoto Y, Miyamura K, Sawa M, Murata M, Karasuno T, Taniguchi S, Nagafuji K, Atsuta Y, Suzuki R, Fukumoto M, Naoe T, Morishita Y

    Cancer Science   Vol. 103 ( 9 ) page: 1688-1694   2012

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  27. Dexamethasone palmitate successfully attenuates hemophagocytic syndrome after allogeneic stem cell transplantation: macrophage-targeted steroid therapy Reviewed

    Nishiwaki S, Nakayama T, Murata M, Nishida T, Sugimoto K, Saito S, Kato T, Mizuno H, Imahashi N, Seto A, Ozawa Y, Goto T, Koyama D, Yokohata E, Kubota N, Kamoshita S, Miyamura K, Matsumoto K, Ito M, Naoe T

    Int J Hematol   Vol. 95 ( 4 ) page: 428-433   2012

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  28. A prospective dose-finding trial using a modified continual reassessment method for optimization of fludarabine plus melphalan conditioning for marrow transplantation from unrelated donors in patients with hematopoietic malignancies Reviewed

    Terakura S, Atsuta Y, Sawa M, Ohashi H, Kato T, Nishiwaki S, Imahashi N, Yasuda T, Murata M, Miyamura K, Suzuki R, Naoe T, Ito T, Morishita Y

    Ann Oncol   Vol. 22 ( 8 ) page: 1865-1875   2011

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  29. Virus-associated hemophagocytic syndrome caused by pandemic swine-origin influenza A (H1N1) in a patient after unrelated bone marrow transplantation Reviewed

    Katsumi A, Nishida T, Murata M, Terakura S, Shimada K, Saito S, Kobayashi M, Kodaira A, Shibata S, Oda I, Yagi T, Kiyoi H, Matsushita T, Kojima T, Naoe T.

    J Clin Exp Hematop   Vol. 51 ( 1 ) page: 63-65   2011

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  30. Feasibility of reduced-intensity cord blood transplantation as salvage therapy for graft failure: results of a nationwide survey of adult patients Reviewed

    Waki F, Masuoka K, Fukuda T, Kanda Y, Nakamae M, Yakushijin K, Togami K, Nishiwaki K, Ueda Y, Kawano F, Kasai M, Nagafuji K, Hagihara M, Hatanaka K, Taniwaki M, Maeda Y, Shirafuji N, Mori T, Utsunomiya A, Eto T, Nakagawa H, Murata M, Uchida T, Iida H, Yakushiji K, Yamashita T, Wake A, Takahashi S, Takaue Y, Taniguchi S.

    Biol Blood Marrow Transplant   Vol. 17 ( 6 ) page: 841-851   2011

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  31. Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic stem cell transplantation Reviewed

    Murase M, Nishida T, Onizuka M, Inamoto Y, Sugimoto K, Imahashi N, Murata M, Miyamura K, Kodera Y, Inoko H, Naoe T

    Bone Marrow Transplant   Vol. 46 ( 11 ) page: 1444-1449   2011

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  32. Donor single nucleotide polymorphism in the CCR9 gene affects the incidence of skin GVHD Reviewed

    InamotoY, Murata M, Katsumi A, Kuwatsuka Y, Tsujimura A, Ishikawa Y, Sugimoto K, Onizuka M, Terakura S, Nishida T, Kanie T, Taji H, Iida H, Suzuki R, Abe1 A, Kiyoi H, Matsushita T, Miyamura K, Kodera Y, Naoe T

    Bone Marrow Transplant   Vol. 45 ( 2 ) page: 363-369   2010

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  33. *CTL clones isolated from an HLA-Cw-mismatched bone marrow transplant recipient with acute graft-versus-host disease Reviewed

    Sugimoto K, Murata M, Terakura S, Naoe T

    J Immunol   Vol. 183 ( 9 ) page: 5991-5998   2009

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  34. Irrespective of CD34 expression, lineage-committed cell fraction reconstitutes and reestablishes transformed Philadelphia chromosome-positive leukemia in NOG mice Reviewed

    Tanizaki R, Nomura Y, Miyata Y, Minami Y, Abe A, Hanamura A, Sawa M, Murata M, Kiyoi H, Matsushita T, Naoe T

    Cancer Sci   Vol. 101 ( 3 ) page: 631-638   2009

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  35. Clinicopathological manifestations and treatment of intestinal transplant-associated microangiopathy (i-TAM) Reviewed

    Inamoto Y, Ito M, Suzuki R, Nishida T, Iida H, Kohno A, Sawa M, Murata M, Nishiwaki S, Oba T, Yanada M, Naoe T, Ichihashi R, Fujino M, Yamaguchi T, Morishita Y, Hirabayashi N, Kodera Y, Miyamura K for the Nagoya Blood and Marrow Transplantation Group

    Bone Marrow Transplant   Vol. 44 ( 1 ) page: 43-49   2009

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  36. *Potential role of a mismatched HLA-specific CTL clone developed pretransplant in graft rejection following cord blood transplantation Reviewed

    Narimatsu H, Murata M, Terakura S, Sugimoto K, Naoe T

    Biol Blood Marrow Transplant   Vol. 14 ( 4 ) page: 397-402   2008

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  37. High incidence of graft failure in unrelated cord blood transplantation using a reduced intensity preparative regimen consisting of fludarabine and melphalan Reviewed

    Narimatsu H, Watanabe M, Kohno A, Sugimoto K, Kuwatsuka Y, Uchida T, Murata M, Miyamura K, Morishita Y

    Bone Marrow Transplant   Vol. 41 ( 8 ) page: 753-756   2008

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  38. Long-term outcome after bone marrow transplantation for aplastic anemia using cyclophosphamide and total lymphoid irradiation as conditioning regimen Reviewed

    Inamoto Y, Miyamura K, Suzuki R, Yasuda T, Takahashi T, Kuwatsuka Y, Tsujimura A, Sugimoto K, Oba T, Terakura S, Atsuta Y, Murata M, Ito M, Kodera Y

    Biol Blood Marrow Transplant   Vol. 14 ( 1 ) page: 43-49   2008

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  39. Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy Reviewed

    Abe A, Minami Y, Hayakawa F, Kitamura K, Nomura Y, Murata M, Katsumi A, Kiyoi H, Jamieson CH, Wang JY, Naoe T

    Int J Hematol   Vol. 88 ( 5 ) page: 471-475   2008

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  40. Donor Cell Leukemia after Allogeneic Peripheral Blood Stem Cell Transplantation: A Case Report and Literature Review Reviewed

    Murata M, Ishikawa Y, Ohashi H, Terakura S, Ozeki K, Kiyoi H, Naoe T

    Int J Hematol   Vol. 88 ( 1 ) page: 111-115   2008

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  41. Clinical characteristics of chronic graft-versus-host disease following umbilical cord blood transplantation for adults Reviewed

    Sugimoto K, Narimatsu H, Kawase T, Iida H, Watanabe M, Kohno A, Kuwatsuka Y, Uchida T, Hamaguchi M, Terakura S, Naoe T, Matsuo K, Murata M, Sawa M, Miyamura K, Morishita Y

    Bone Marrow Transplant   Vol. 41 ( 8 ) page: 729-736   2008

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  42. Decreased Risk of Acute Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients with the 5,10-Methylenetetrahydrofolate Reductase 677TT Genotype Reviewed

    Sugimoto K, Murata M, Onizuka M, Inamoto Y, Terakura S, Kuwatsuka Y, Oba T, Miyamura K, Kodera Y, Naoe T

    Int J Hematol   Vol. 87 ( 5 ) page: 451-458   2008

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  43. Successful second cord blood transplantation using fludarabine and cyclophosphamide as a preparative regimen for graft rejection following reduced-intensity cord blood transplantation Reviewed

    Mizutani E, Narimatsu H, Murata M, Tomita A, Kiyoi H, Naoe T

    Bone Marrow Transplant   Vol. 40 ( 1 ) page: 85-87   2007

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  44. Hematopoietic engraftment in recipients of unrelated donor umbilical cord blood is affected by the CD34+ and CD8+ cell doses Reviewed

    Terakura S, Azuma E, Murata M, Kumamoto T, Hirayama M, Atsuta Y, Kodera Y, Yazaki M, Naoe T, Kato K

    Biol Blood Marrow Transplant   Vol. 13 ( 7 ) page: 822-830   2007

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  45. *A single minor histocompatibility antigen encoded by UGT2B17 and presented by HLA-A*2902 and B*4403 Reviewed

    Terakura S, Murata M, Warren EH, Sette A, Sidney J, Naoe T, Riddell SR

    Transplantation   Vol. 83 ( 9 ) page: 1242-1248   2007

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  46. Successful umbilical cord blood transplantation using a reduced-intensity preparative regimen without total body irradiation and tacrolimus plus methotrexate for prophylaxis of graft-versus-host disease in a patient with adult T-cell leukemia/lymphoma Reviewed

    Narimatsu H, Murata M, Sugimoto K, Terakura S, Kinoshita T, Naoe T

    Leukemia Lymphoma   Vol. 48 ( 4 ) page: 841-843   2007

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  47. Short-term methotrexate could reduce early immune reactions and improve outcomes in umbilical cord blood transplantation for adults Reviewed

    Narimatsu H, Terakura S, Matsuo K, Oba T, Uchida T, Iida H, Hamaguchi M, Watanabe M, Kohno A, Murata M, Sawa M, Miyamura K, Morishita Y

    Bone Marrow Transplant   Vol. 39 ( 1 ) page: 31-39   2007

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  48. Increased risk for treatment-related mortality after bone marrow transplantation in GSTM1-positive recipients Reviewed

    Terakura S, Murata M, Nishida T, Emi N, Akatsuka Y, Morishima Y, Kodera Y, Naoe T

    Bone Marrow Transplant   Vol. 37 ( 4 ) page: 381-386   2006

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  49. Micafungin, a novel antifungal agent, as empirical therapy in acute leukemia patients with febrile neutropenia Reviewed

    Yanada M, Kiyoi H, Murata M, Suzuki M, Iwai M, Yokozawa T, Baba H, Emi N, Naoe T

    Internal Med   Vol. 45 ( 5 ) page: 259-264   2006

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  50. Stable engraftment after a conditioning regimen with fludarabine and melphalan for bone marrow transplantation from an unrelated donor Reviewed

    Inamoto Y, Oba T, Miyamura K, Terakura S, Tsujimura A, Kuwatsuka Y, Tokunaga M, Kasai M, Murata M, Naoe T, Kodera Y

    Int J Hematol   Vol. 83 ( 4 ) page: 356-362   2006

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  51. Mutations of N-RAS, FLT3 and p53 genes are not involved in the development of acute leukemia transformed from myeloproliferative diseases with JAK2 mutation Reviewed

    Suzuki M, Abe A, Kiyoi H, Murata M, Ito Y, Shimada K, Morishita Y, Kinoshita T, Naoe T

    Leukemia   Vol. 20 ( 6 ) page: 1168-1169   2006

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  52. Titer of ADAMTS13 inhibitor associated with thrombotic microangiopathy of the gut and skeletal muscle after allogeneic hematopoietic stem cell transplantation Reviewed

    Adachi T, Matsushita T, Ichihashi R, Hirashima K, Ito M, Inukai A, Yokozawa T, Nishida T, Murata M, Hayashi M, Katsumi A, Kojima T, Saito H, Naoe T

    Int J Hematol   Vol. 83 ( 5 ) page: 415-419   2006

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  53. Identification and frequency of a new HLA-A allele, A*030104 Reviewed

    Murata M, Emi N, Izumisawa Y, Inaki A, Saitoh M, Naoe T

    Tissue Antigens   Vol. 65 ( 4 ) page: 391-392   2005

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  54. *A UGT2B17-positive donor is a risk factor for higher transplant-related mortality and lower survival after bone marrow transplantation Reviewed

    Terakura S, Murata M, Nishida T, Emi N, Akatsuka Y, Riddell SR, Morishima Y, Kodera Y, Naoe T

    Brit J Haematol   Vol. 129 ( 2 ) page: 221-228   2005

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  55. GSTT1 and GSTM1 deletions, NQO1 C609T polymorphism and risk of chronic myelogenous leukemia in Japanese Reviewed

    Hishida A, Terakura S, Emi N, Yamamoto K, Murata M, Nishio K, Sekido Y, Niwa T, Hamajima N, Naoe T

    Asian Pac J Cancer Prev   Vol. 6 ( 3 ) page: 251-255   2005

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  56. Intestinal thrombotic microangiopathy after allogeneic bone marrow transplantation: a clinical imitator of acute enteric graft-versus-host disease Reviewed

    Nishida T, Hamaguchi M, Hirabayashi N, Haneda M, Terakura S, Atsuta Y, Imagama S, Kanie T, Murata M, Taji H, Suzuki R, Morishita Y, Kodera Y

    Bone Marrow Transplant   Vol. 33 ( 11 ) page: 1143-1150   2004

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  57. A human minor histocompatibility antigen resulting from differential expression due to a gene deletion Reviewed

    *Murata M, Warren EH, Riddell SR

    J Exp Med   Vol. 197 ( 10 ) page: 1279-1289   2003

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  58. The graft versus leukemia response after allogeneic hematopoietic stem cell transplantation Reviewed

    Riddell SR, Berger C, Murata M, Randolph S, Warren EH

    Blood Rev   Vol. 17 ( 3 ) page: 153-162   2003

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  59. Prognostic significance of CD7+CD56+ phenotype and chromosome 5 abnormalities for acute myeloid leukemia M0 Reviewed

    Suzuki R, Murata M, Kami M, Ohtake S, Asou N, Kodera Y, Tomonaga M, Masaki Y, Kusumoto S, Takeuchi J, Matsuda S, Hirai H, Yorimitsu S, Hamajima N, Seto M, Shimoyama M, Ohno R, Morishima Y, Nakamura S

    Int J Hematol   Vol. 77 ( 5 ) page: 482-488   2003

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  60. T-cell therapy targeting minor histocompatibility Ags for the treatment of leukemia and renal-cell carcinoma Reviewed

    Warren EH, Tykodi SS, Murata M, Sandmaier BM, Storb R, Jaffee E, Childs R, Greenberg PD, Riddell SR

    Cytotherapy   Vol. 4 ( 5 ) page: 441-441   2002

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  61. T-cell therapy of leukemia Invited Reviewed

    Riddell SR, Murata M, Bryant S, Warren EH

    Cancer Control (Journal of the Moffitt Cancer Center)   Vol. 9 ( 2 ) page: 114-122   2002

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  62. Minor histocompatibility antigens--targets of graft versus leukemia responses Reviewed

    Riddell SR, Murata M, Bryant S, Warren EH

    Int J Hematol   Vol. 76   page: 155-161   2002

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  63. Non-myeloablative transplants for malignant disease Invited

    Storb RF, Champlin R, Riddell SR, Murata M, Bryant S, Warren EH

    Hematology Am Soc Hematol Educ Program     page: 375-391   2001

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  64. Apoptotic cytotoxic effects of a histone deacetylase inhibitor, FK228, on malignant lymphoid cells Reviewed

    Murata M, Towatari M, Kosugi H, Tanimoto M, Ueda R, Saito H, Naoe T

    Jpn J Cancer Res (Cancer Sci)   Vol. 91 ( 11 ) page: 1154-1160   2000

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  65. No significant association between HA-1 incompatibility and incidence of acute graft-versus-host disease after HLA-identical sibling bone marrow transplantation in Japanese patients Reviewed

    Murata M, Emi N, Hirabayashi N, Hamaguchi M, Goto S, Wakita A, Tanimoto M, Saito H, Kodera Y, Morishita Y

    Int J Hematol   Vol. 72 ( 3 ) page: 371-375   2000

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  66. A new preconditioning regimen with melphalan, busulphan and total body irradiation followed by low-dose immunosuppressant in allogeneic haemopoietic stem cell transplantation Reviewed

    Murata M, Nishida T, Haneda M, Kanie T, Taji H, Iida H, Suzuki R, Hamaguchi M, Minami S, Kodera Y

    Brit J Haematol   Vol. 105 ( 3-4 ) page: 799-802   1999

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  67. Peripheral blood stem cells mobilization and apheresis: analysis of adverse events in 94 normal donors Reviewed

    Murata M, Harada M, Kato S, Takahashi S, Ogawa H, Okamoto S, Tsuchiya S, Sakamaki H, Akiyama Y, Kodera Y

    Bone Marrow Transplant   Vol. 24 ( 10 ) page: 1065-1071   1999

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  68. Bone marrow transplantation in Japanese patients is facilitated by the National Marrow Donor Program of the U.S. Reviewed

    Murata M, Haneda M, Nishida T, Kanie T, Hamaguchi M, Minami S, Kodera Y

    Transplant P   Vol. 30 ( 1 ) page: 150-152   1998

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  69. Hepatic injury localized to the field of total lymphoid irradiation Reviewed

    Murata M, Muramoto H, Kojima Y, Nishida T, Haneda M, Kanie T, Taji H, Hamaguchi M, Minami S, Imaeda T, Kodera Y

    Bone Marrow Transplant   Vol. 20 ( 10 ) page: 897-899   1997

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  70. Unrelated bone marrow transplantation from the National Marrow Donor Program Reviewed

    Murata M, Kanie T, Hamaguchi M, Nishida T, Haneda M, Minami S, Kodera Y

    Int J Hematol   Vol. 66 ( 12 ) page: 239-243   1997

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  71. Serum thrombopoietin level after allogeneic bone marrow transplantation: possible correlations with platelet recovery, acute graft-versus-host disease and hepatic veno-occlusive disease Reviewed

    Hamaguchi M, Yamada H, Morishima Y, Morishita Y, Kato Y, Sao H, Kanie T, Murata M, Taji H, Nakayama Y, Minami S, Saito H, Kodera Y

    Int J Hematol   Vol. 64 ( 3-4 ) page: 241-248   1996

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  72. Off-the-shelf bone marrow-derived mesenchymal stem cell treatment for acute graft-versus-host disease: real-world evidence Reviewed

    Murata Makoto, Terakura Seitaro, Wake Atsushi, Miyao Kotaro, Ikegame Kazuhiro, Uchida Naoyuki, Kataoka Keisuke, Miyamoto Toshihiro, Onizuka Makoto, Eto Tetsuya, Doki Noriko, Ota Shuichi, Sato Maho, Hashii Yoshiko, Ichinohe Tatsuo, Fukuda Takahiro, Atsuta Yoshiko, Okamoto Shinichiro, Teshima Takanori

    BONE MARROW TRANSPLANTATION   Vol. 56 ( 10 ) page: 2355 - 2366   2021.10

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  73. Total body irradiation-containing conditioning regimens without antithymocyte globulin in adults with aplastic anemia undergoing umbilical cord blood transplantation. Reviewed

    Hiramoto N, Yamazaki H, Nakamura Y, Uchida N, Murata M, Kondo T, Yoshioka S, Eto T, Nishikawa A, Kimura T, Ichinohe T, Atsuta Y, Onishi Y, Suzuki R, Mori T, Adult Aplastic Anemia Working Group of the Japanese Society for Hematopoietic Cell Transplantation.

    Annals of hematology     2021.9

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    DOI: 10.1007/s00277-021-04664-z

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  74. Impact of HLA disparity on the risk of overall mortality in patients with grade II-IV acute GVHD on behalf of the HLA Working Group of Japan Society for Hematopoietic Cell Transplantation Reviewed

    Fuji Shigeo, Hakoda Akitoshi, Kanda Junya, Murata Makoto, Terakura Seitaro, Inamoto Yoshihiro, Uchida Naoyuki, Toya Takashi, Eto Tetsuya, Nakamae Hirohisa, Ikegame Kazuhiro, Tanaka Masatsugu, Kawakita Toshiro, Kondo Tadakazu, Miyamoto Toshihiro, Fukuda Takahiro, Ichinohe Tatsuo, Kimura Takafumi, Atsuta Yoshiko, Shintani Ayumi, Morishima Satoko

    BONE MARROW TRANSPLANTATION     2021.9

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  75. Composite CD79A/CD40 co-stimulatory endodomain enhances CD19CAR-T cell proliferation and survival Reviewed

    Julamanee Jakrawadee, Terakura Seitaro, Umemura Koji, Adachi Yoshitaka, Miyao Kotaro, Okuno Shingo, Takagi Erina, Sakai Toshiyasu, Koyama Daisuke, Goto Tatsunori, Hanajiri Ryo, Hudecek Michael, Steinberger Peter, Leitner Judith, Nishida Tetsuya, Murata Makoto, Kiyoi Hitoshi

    MOLECULAR THERAPY   Vol. 29 ( 9 ) page: 2677 - 2690   2021.9

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  76. Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease Using Commercial Mesenchymal Stem Cell Products Reviewed

    Murata Makoto, Teshima Takanori

    FRONTIERS IN IMMUNOLOGY   Vol. 12   page: 724380   2021.8

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  77. Spacer Length Modification Facilitates Discrimination between Normal and Neoplastic Cells and Provides Clinically Relevant CD37 CAR T Cells Reviewed

    Okuno Shingo, Adachi Yoshitaka, Terakura Seitaro, Julamanee Jakrawadee, Sakai Toshiyasu, Umemura Koji, Miyao Kotaro, Goto Tatsunori, Murase Atsushi, Shimada Kazuyuki, Nishida Tetsuya, Murata Makoto, Kiyoi Hitoshi

    JOURNAL OF IMMUNOLOGY   Vol. 206 ( 12 ) page: 2862 - 2874   2021.6

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  78. Combined impact of HLA-allele matching and the CD34-positive cell dose on optimal unit selection for single-unit cord blood transplantation in adults. Reviewed

    Yabe T, Satake M, Odajima T, Watanabe-Okochi N, Azuma F, Kashiwase K, Matsumoto K, Orihara T, Yabe H, Kato S, Kato K, Kai S, Mori T, Morishima S, Takanashi M, Nakajima K, Murata M, Morishima Y

    Leukemia & lymphoma     page: 1 - 10   2021.6

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    DOI: 10.1080/10428194.2021.1929958

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  79. Comparison of Transplantation Outcomes after Foscarnet and Ganciclovir Administration as First-Line Anti-Cytomegalovirus Preemptive Therapy Reviewed

    Miyao Kotaro, Terakura Seitaro, Ozawa Yukiyasu, Sawa Masashi, Kohno Akio, Kasahara Senji, Iida Hiroatsu, Ino Kazuko, Kusumoto Shigeru, Kasai Masanobu, Takami Akiyoshi, Kurahashi Shingo, Kajiguchi Tomohiro, Morishita Takanobu, Nishida Tetsuya, Murata Makoto

    TRANSPLANTATION AND CELLULAR THERAPY   Vol. 27 ( 4 ) page: 342.e1 - 342.e10   2021.4

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  80. Effect of methotrexate dose in graft-versus-host disease prophylaxis after single-unit cord blood transplantation in adult acute myeloid leukemia

    Terakura Seitaro, Kuwatsuka Yachiyo, Sugita Junichi, Takahashi Satoshi, Ozawa Yukiyasu, Ozeki Kazutaka, Yoshioka Satoshi, Nakamae Hirohisa, Kawakita Toshiro, Sawa Masashi, Morishige Satoshi, Najima Yuho, Katsuoka Yuna, Sakaida Emiko, Kouzai Yasuji, Kimura Takafumi, Ichinohe Tatsuo, Fukuda Takahiro, Atsuta Yoshiko, Murata Makoto, Teshima Takanori

    INTERNATIONAL JOURNAL OF HEMATOLOGY     2021.2

  81. A multicenter phase II study of intrabone single-unit cord blood transplantation without antithymocyte globulin

    Nishida Tetsuya, Kobayashi Takeshi, Sawa Masashi, Masuda Shinichi, Shibasaki Yasuhiko, Goto Tatsunori, Fukuhara Noriko, Fujii Nobuharu, Ikegame Kazuhiro, Sugita Junichi, Ikeda Takashi, Kuwatsuka Yachiyo, Suzuki Ritsuro, Najima Yuho, Doki Noriko, Kato Tomonori, Inagaki Yuichiro, Utsu Yoshikazu, Aotsuka Nobuyuki, Masuko Masayoshi, Terakura Seitaro, Onishi Yasushi, Maeda Yoshinobu, Okada Masaya, Teshima Takanori, Murata Makoto

    ANNALS OF HEMATOLOGY     2021.1

  82. Phase I clinical trial of intra-bone marrow cotransplantation of mesenchymal stem cells in cord blood transplantation Reviewed International journal

    Goto Tatsunori, Murata Makoto, Nishida Tetsuya, Terakura Seitaro, Kamoshita Sonoko, Ishikawa Yuichi, Ushijima Yoko, Adachi Yoshiya, Suzuki Satoshi, Kato Katsuyoshi, Hirakawa Akihiro, Nishiwaki Satoshi, Nishio Nobuhiro, Takahashi Yoshiyuki, Kodera Yoshihisa, Matsushita Tadashi, Kiyoi Hitoshi

    STEM CELLS TRANSLATIONAL MEDICINE     2020.12

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    DOI: 10.1002/sctm.20-0381

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  83. Artificial T Cell Adaptor Molecule-Transduced TCR-T Cells Demonstrated Improved Proliferation Only When Transduced in a Higher Intensity Reviewed International journal

    Sakai Toshiyasu, Terakura Seitaro, Miyao Kotaro, Okuno Shingo, Adachi Yoshitaka, Umemura Koji, Julamanee Jakrawadee, Watanabe Keisuke, Hamana Hiroshi, Kishi Hiroyuki, Leitner Judith, Steinberger Peter, Nishida Tetsuya, Murata Makoto, Kiyoi Hitoshi

    MOLECULAR THERAPY-ONCOLYTICS   Vol. 18   page: 613 - 622   2020.9

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    DOI: 10.1016/j.omto.2020.08.014

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  84. Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelodysplastic/Myeloproliferative Neoplasms-Unclassifiable: A Retrospective Nationwide Study of the Japan Society for Hematopoietic Cell Transplantation

    Kurosawa Shuhei, Shimomura Yoshimitsu, Tachibana Takayoshi, Ishiyama Ken, Ota Shuichi, Kobayashi Takeshi, Uchida Naoyuki, Fukushima Kentaro, Ashida Takashi, Matsuoka Ken-ichi, Kanda Junya, Ichinohe Tatsuo, Atsuta Yoshiko, Murata Makoto, Aoki Jun

    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION   Vol. 26 ( 9 ) page: 1607 - 1611   2020.9

  85. Effect of graft-versus-host disease on outcomes after pediatric single cord blood transplantation

    Kanda Junya, Umeda Katsutsugu, Kato Koji, Murata Makoto, Sugita Junichi, Adachi Souichi, Koh Katsuyoshi, Noguchi Maiko, Goto Hiroaki, Yoshida Nao, Sato Maho, Koga Yuhki, Hori Tsukasa, Cho Yuko, Ogawa Atsushi, Inoue Masami, Hashii Yoshiko, Atsuta Yoshiko, Teshima Takanori

    BONE MARROW TRANSPLANTATION   Vol. 55 ( 7 ) page: 1430 - 1437   2020.7

  86. Capturing Differential Allele-Level Expression and Genotypes of All Classical HLA Loci and Haplotypes by a New Capture RNA-Seq Method

    Yamamoto Fumiko, Suzuki Shingo, Mizutani Akiko, Shigenari Atsuko, Ito Sayaka, Kametani Yoshie, Kato Shunichi, Fernandez-Vina Marcelo, Murata Makoto, Morishima Satoko, Morishima Yasuo, Tanaka Masafumi, Kulski Jerzy K., Bahram Seiamak, Shiina Takashi

    FRONTIERS IN IMMUNOLOGY   Vol. 11   2020.5

  87. Prospective evaluation of alternative donor from unrelated donor and cord blood in adult acute leukemia and myelodysplastic syndrome. Reviewed International journal

    Seitaro Terakura, Tetsuya Nishida, Masashi Sawa, Tomonori Kato, Kotaro Miyao, Yukiyasu Ozawa, Tatsunori Goto, Akio Kohno, Kazutaka Ozeki, Yasushi Onishi, Noriko Fukuhara, Nobuharu Fujii, Hisayuki Yokoyama, Masanobu Kasai, Hiroatsu Iida, Nobuhiro Kanemura, Tomoyuki Endo, Hiroatsu Ago, Makoto Onizuka, Satoshi Iyama, Yuichiro Nawa, Mika Nakamae, Yasuyuki Nagata, Shingo Kurahashi, Yasuo Tomiya, Atsumi Yanagisawa, Ritsuro Suzuki, Yachiyo Kuwatsuka, Yoshiko Atsuta, Koichi Miyamura, Makoto Murata

    Bone marrow transplantation   Vol. 55 ( 7 ) page: 1399 - 1409   2020.3

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    A prospectively registered observational study was conducted to assess the significance of allogeneic hematopoietic stem cell transplantation from highly HLA-matched unrelated donors (UD) and cord blood (CB) on outcomes in adult acute leukemia (AL) and myelodysplastic syndrome (MDS). Between 2007 and 2015, 231 transplant-eligible patients were registered for a phase 2 study of alternative donor transplantation. After registration, a sufficient time period was given to find appropriate UD. Patients received CB transplantation (CBT) if an appropriate UD was unavailable. In total, 119 patients received CBT (106 AL and 13 MDS) and 91 patients received UD transplantation (UDT) (86 AL and 5 MDS). The median age was 39 years in both groups. The primary objective was overall survival (OS); secondary objectives included cumulative incidences of non-relapse mortality (NRM) and relapse, and disease-free survival. Diagnosis, disease status at transplantation, refined disease risk index, and hematopoietic cell transplant-specific comorbidity index did not differ between UDT and CBT. In multivariate analyses, graft source was not a significant risk factor for all objectives. In adjusted analyses, UDT and CBT showed similar OS, NRM, and relapse in this prospective study. CB can be a comparable alternative stem cell source to UD by achieving a timely transplant.

    DOI: 10.1038/s41409-020-0859-8

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  88. Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning. Reviewed

    Seitaro Terakura, Makoto Onizuka, Mariko Fukumoto, Yachiyo Kuwatsuka, Akio Kohno, Yukiyasu Ozawa, Koichi Miyamura, Yuichiro Inagaki, Masashi Sawa, Yoshiko Atsuta, Ritsuro Suzuki, Tomoki Naoe, Yoshihisa Morishita, Makoto Murata

    International journal of hematology   Vol. 111 ( 1 ) page: 84 - 92   2020.1

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    Sporadic incidence of veno-occlusive disease (VOD) continues to occur, despite achievement of recommended busulfan (BU) concentrations after real-time BU dose adjustment. To explore the potential influence of glutathione S-transferase (GST) and cytochrome P450 (CYP) genotypes on plasma BU concentration, subsequent VOD, and transplant outcome, we assessed the polymorphisms of multiple GST and CYP genes. Fifty-five patients were included (median age 38 years; range 21-67). Of these, 49 received dose-adjusted BU/CY therapy. Twenty-six patients received transplants from human leukocyte antigen-identical siblings, 26 from unrelated donors. The GSTA1*A/*A genotype was significantly associated with lower BU first-dose area under curve (AUC1st). We found that patients with higher AUC1st showed a significantly higher serum total bilirubin during the first month after transplantation, but this was not necessarily associated with subsequent development of VOD. We further analyzed a possible association of GST and CYP polymorphisms and VOD development, and found none of the polymorphisms investigated was associated with VOD incidence. Regarding transplant outcomes, GSTM1-positive patients showed lower relapse rates and better overall survival in multivariate analyses. These results suggest that a GSTM1-positive genotype in patients receiving BU/CY conditioning protects against relapse of hematological malignancies after allogeneic hematopoietic stem cell transplantation.

    DOI: 10.1007/s12185-019-02741-8

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  89. Correction to: Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning. Reviewed

    Seitaro Terakura, Makoto Onizuka, Mariko Fukumoto, Yachiyo Kuwatsuka, Akio Kohno, Yukiyasu Ozawa, Koichi Miyamura, Yuichiro Inagaki, Masashi Sawa, Yoshiko Atsuta, Ritsuro Suzuki, Tomoki Naoe, Yoshihisa Morishita, Makoto Murata

    International journal of hematology   Vol. 111 ( 1 ) page: 159 - 160   2020.1

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    In the original article of Terakura et al., the COI disclosure were missing.

    DOI: 10.1007/s12185-019-02783-y

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  90. Donor single nucleotide polymorphism in ACAT1 affects the incidence of graft-versus-host disease after bone marrow transplantation. Reviewed

    Sonoko Kamoshita, Makoto Murata, Daisuke Koyama, Jakrawadee Julamanee, Shingo Okuno, Erina Takagi, Kotaro Miyao, Tatsunori Goto, Yukiyasu Ozawa, Koichi Miyamura, Seitaro Terakura, Tetsuya Nishida, Hitoshi Kiyoi

    International journal of hematology   Vol. 111 ( 1 ) page: 112 - 119   2020.1

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    Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1) is an enzyme that converts cholesterol to cholesteryl esters. A recent in vivo study reported that inhibiting ACAT1 enzyme activity upregulates the membrane cholesterol levels of T cells, enhancing their cytotoxic function. In the present study, we investigated whether the presence of the ACAT1 single nucleotide polymorphism rs11545566 in transplant donors affected the risk of graft-versus-host disease (GVHD) in 116 adult patients who underwent bone marrow transplantation from human leukocyte antigen-identical sibling donors, and who received GVHD prophylaxis with short-term methotrexate and cyclosporine. The frequencies of the AA, AG, and GG genotypes in the donors were 31%, 45%, and 24%, respectively. The cumulative incidences of grade II-IV acute GVHD on day 100 in patients whose donors had AA vs. non-AA genotypes were 6% and 18%, respectively, and those of extensive chronic GVHD at 2 years were 7% and 32%, respectively. Multivariate analyses demonstrated that donor rs11545566 non-AA genotypes showed a trend toward a higher incidence of grade II-IV acute GVHD (P = 0.079), and were significantly associated with a higher incidence of extensive chronic GVHD (P = 0.021). These results suggest that donor ACAT1 rs11545566 genotype may be predictive of GVHD.

    DOI: 10.1007/s12185-019-02739-2

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  91. Prospective Phase 2 Study of Umbilical Cord Blood Transplantation in Adult Acute Leukemia and Myelodysplastic Syndrome. Reviewed International journal

    Seitaro Terakura, Tetsuya Nishida, Masashi Sawa, Tomonori Kato, Kotaro Miyao, Yukiyasu Ozawa, Akio Kohno, Yasushi Onishi, Noriko Fukuhara, Masanobu Kasai, Nobuharu Fujii, Hisayuki Yokoyama, Hiroatsu Iida, Nobuhiro Kanemura, Atsushi Fujieda, Hiroatsu Ago, Yutaka Tsutsumi, Fumihiko Nakamura, Kazuhiro Yago, Yukiyoshi Moriuchi, Shuichi Ota, Haruhiko Ohashi, Atsumi Yanagisawa, Ritsuro Suzuki, Yachiyo Kuwatsuka, Yoshiko Atsuta, Koichi Miyamura, Makoto Murata

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   Vol. 26 ( 1 ) page: 139 - 144   2020.1

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    Almost comparable transplantation outcomes have been reported with HLA-matched unrelated donor transplantation (UDT) and cord blood transplantation (CBT). We conducted a prospective phase 2 study to assess the efficacy and safety of single-unit myeloablative CBT in adult leukemia and myelodysplastic syndrome. Because the day 180 survival of UDT was approximately 80%, we determined the alternative hypothesis of expected day 180 survival with a successful engraftment rate of 80% and set the null hypothesis of threshold rate at 65%. Sixty-two patients (median age, 37 years) were registered, including 28 with acute myelogenous leukemia, 25 with acute lymphoblastic leukemia, and 9 with myelodysplastic syndrome. Of 61 eligible patients, 52 were successfully engrafted and survived at day 180 (85%; 95% confidence interval, 74% to 93%). Single-unit CBT was judged to be effective because the null hypothesis was rejected (P < .001). Furthermore, neutrophil engraftment was observed in 57 patients (92%); the incidences of grade II-IV acute and chronic graft-versus-host disease were 30% and 32%, respectively; and the cumulative incidences of nonrelapse mortality and relapse at 2 years were 18% and 13%, respectively. The present study showed favorable survival outcomes with single-unit CBT. Therefore, this method may be considered if a well-HLA-matched UDT cannot be obtained.

    DOI: 10.1016/j.bbmt.2019.09.021

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  92. Impact of Homozygous Conserved Extended HLA Haplotype on Single Cord Blood Transplantation: Lessons for Induced Pluripotent Stem Cell Banking and Transplantation in Allogeneic Settings. Reviewed International journal

    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

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   Vol. 26 ( 1 ) page: 132 - 138   2020.1

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    Induced pluripotent stem cells (iPSCs) have been applied to clinical regenerative cell therapy. Recently, an iPSC banking system to collect HLA haplotype (HP) homozygous (homo) cells for iPSC transplantation in allogeneic settings was proposed, and tissue transplantation generated from iPSC through banking has just began. We analyzed 5017 single cord blood transplantation (CBT) pairs with HLA-A, -B, -C, -DRB1 allele typing data and found 39 donor HLA homo donor to patient HLA heterozygous (hetero) pairs. Of note, all 39 HLA homo to hetero pairs engrafted neutrophils, except 1 early death pair, and all 30 assessable pairs engrafted platelets. Acute graft-versus-host disease (GVHD) grades II to IV and grades III to IV occurred in 17 and 3 of 38 assessable pairs, respectively. Competing risk regression analysis revealed a favorable risk of neutrophil engraftment and higher risk of acute GVHD compared with HLA-matched CBTs. Thirty-seven of 39 homo to hetero pairs had conserved extended HLA HPs (HP-1, n = 18; HP-2, n = 8; HP-3, n = 7; HP-4, n = 4; HP-5, n = 1) that were ethnicity-specific, and at least 1 of 2 patient HLA-A, -B, -C, and -DRB1 alleles in each locus were invariably shared with the same donor HP in 35 pairs. These findings confirmed our preliminary results with 6 HLA homo CBTs, and a trend of high incidence of acute GVHD was newly observed. Importantly, they imply the possibility that HLA-homo iPSC transplantation provides favorable engraftment and accordingly imply the merit of banking iPSC with homozygous major conserved extended HLA HPs.

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  93. Capturing Differential Allele-Level Expression and Genotypes of All Classical HLA Loci and Haplotypes by a New Capture RNA-Seq Method Reviewed

    Yamamoto F, Suzuki S, Mizutani A, Shigenari A, Ito S, Kametani Y, Kato S, Fernandez-Viña M, Murata M, Morishima S, Morishima Y, Tanaka M, Kulski JK, Bahram S, Shiina T

    Front Immunol   Vol. 11   page: 941   2020

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  94. Allogeneic Hematopoietic Stem Cell Transplantation for Post-essential Thrombocythemia and Post-polycythemia Vera Myelofibrosis Reviewed

    Murata M, Suzuki R, Nishida T, Shirane S, Shimazu Y, Minami Y, Mori T, Doki N, Kanda Y, Uchida N, Tanaka M, Ishikawa J, Togitani K, Fukuda T, Ichinohe T, Atsuta Y, Nagamura-Inoue T, Kiyoi H

    Internal Med   Vol. 59   page: 1947 - 1956   2020

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  95. Successful introduction of peritoneal dialysis in an end-stage renal failure patient with idiopathic aplastic anemia Reviewed

    Suzuki Y, Mizuno M, Sakata F, Kojima H, Sato Y, Kishimoto M, Suzuki N, kinashi H, Saito S, Katsuno T, Kosugi T, Maruyama S, Murata M, Kiyoi H, Ito Y

    Internal Medicine   Vol. 59 ( 5 ) page: 683 - 687   2020

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  96. 分子標的薬・免疫療法薬の血液合併症 Invited Reviewed

    村田誠

    日本医師会雑誌   Vol. 148 ( 10 ) page: 1964 - 1964   2020

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  97. 間葉系幹細胞を用いた細胞療法 Invited Reviewed

    村田誠

    日本アフェレシス学会雑誌   Vol. 39 ( 1 ) page: 34 - 39   2020

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  98. 臍帯血移植生着前に発症し高用量liposomal amphotericin Bで救命しえた播種性Fusarium感染症 Reviewed

    原田 靖彦, 村田 誠, 松本 あかね, 加藤 大三, 八木 哲也, 矢口 貴志, 吉川 剛典, 武市 拓也, 秋山 真志, 山口 洋平, 小山 大輔, 寺倉 精太郎, 西田 徹也, 清井 仁

    臨床血液   Vol. 60 ( 12 ) page: 1641 - 1646   2019.12

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    骨髄移植後に再発した骨髄異形成関連変化を伴う急性骨髄性白血病患者(47歳,男性)に臍帯血移植を実施した。生着前に広域抗菌薬不応の発熱性好中球減少症および全身性の有痛性結節が出現した。皮膚生検と血液培養で糸状菌を認め真菌血症と診断,さらに培養コロニーの検鏡,質量分析,塩基配列決定からFusarium solaniによる播種性感染症と確定診断した。Liposomal amphotericin B(L-AMB)5mg/kg/日の投与により熱型と皮疹は改善し始めた。Day19に生着し,皮膚急性移植片対宿主病stage3は外用ステロイド剤で寛解した。Day38にvoriconazoleへ変更したところFusarium感染症は増悪した。その後はL-AMB計19週間の投与で治癒した。生着前の播種性Fusarium感染症は極めて予後不良である。本症例では,好中球の生着に加え,速やかな確定診断,適切な抗真菌薬の選択,その十分量かつ長期間の投与,ステロイド剤全身投与回避などが功を奏したと考えられた。(著者抄録)

  99. Comparison of Outcomes of Allogeneic Transplantation for Primary Myelofibrosis among Hematopoietic Stem Cell Source Groups. Reviewed International journal

    Makoto Murata, Katsuto Takenaka, Naoyuki Uchida, Yukiyasu Ozawa, Kazuteru Ohashi, Sung-Won Kim, Kazuhiro Ikegame, Yoshinobu Kanda, Hikaru Kobayashi, Jun Ishikawa, Hiroatsu Ago, Makoto Hirokawa, Takahiro Fukuda, Yoshiko Atsuta, Takeshi Kondo

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   Vol. 25 ( 8 ) page: 1536 - 1543   2019.8

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    The choice of alternative donor is a major issue in allogeneic hematopoietic stem cell transplantation (HSCT) for patients with primary myelofibrosis (PMF) without an HLA-matched related donor. We conducted this retrospective study using the Japanese national registry data for 224 PMF patients to compare the outcomes of first allogeneic HSCT from HLA-matched related donor bone marrow (Rtd-BM), HLA-matched related donor peripheral blood stem cells (Rtd-PB), HLA-matched unrelated donor bone marrow (UR-BM), unrelated umbilical cord blood (UR-UCB), and other hematopoietic stem cell grafts. Nonrelapse mortality (NRM) rates at 1 year after Rtd-BM, Rtd-PB, UR-BM, UR-UCB, and other transplantations were 16%, 36%, 30%, 41%, and 48%, respectively. Multivariate analysis identified UR-UCB transplantation, other transplantation, frequent RBC transfusion before transplantation, and frequent platelet (PLT) transfusion before transplantation as predictive of higher NRM. Relapse rates at 1 year after Rtd-BM, Rtd-PB, UR-BM, UR-UCB, and other transplantation were 14%, 17%, 11%, 14%, and 15%, respectively. No specific factor was associated with the incidence of relapse. Overall survival (OS) at 1 and 4 years after Rtd-BM, Rtd-PB, UR-BM, UR-UCB, and other transplantation were 81% and 71%, 58% and 52%, 61% and 46%, 48% and 27%, and 48% and 41%, respectively. Multivariate analysis identified older patient age, frequent RBC transfusion before transplantation, and frequent PLT transfusion before transplantation as predictive of lower OS. In conclusion, UR-UCB transplantation, as well as UR-BM transplantation, can be selected for PMF patients without an HLA-identical related donor. However, careful management is required for patients after UR-UCB transplantation because of the high NRM. Further studies including more patients after HLA-haploidentical related donor and HLA-mismatched unrelated donor transplantation would provide more valuable information for patients with PMF when making decisions regarding the choice of alternative donor.

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  100. Effects of HLA mismatch on cytomegalovirus reactivation in cord blood transplantation

    Yokoyama Hisayuki, Kanda Junya, Kato Shunichi, Kondo Eisei, Maeda Yoshinobu, Saji Hiroo, Takahashi Satoshi, Onizuka Makoto, Onishi Yasushi, Ozawa Yukiyasu, Kanamori Heiwa, Ishikawa Jun, Ohno Yuju, Ichinohe Tatsuo, Takanashi Minoko, Kato Koji, Atsuta Yoshiko, Kanda Yoshinobu, Ikegame Kazuhiro, Utsunomiya Atae, Kawase Takakazu, Kim Sung-Won, Kuwatsuka Yachiyo, Kobayashi Takeshi, Takatsuka Yoshifusa, Takahashi Yoshiyuki, Tanaka Junji, Tamaki Hiroya, Tsuji Masanori, Nishida Tetsuya, Masuko Masayoshi, Matsuno Ryosuke, Murata Makoto, Morishima Satoko, Morishima Yasuo, Yokoyama Hisayuki, Wake Atsushi, Watanabe Nobuhiro, Ashida T., Hoshino Takumi, Yabe Toshio, Sakamoto Kana, Fuji Shigeo, Miyamura Koichi, Arima Nobuyoshi, Kondo Eisei, Yoshimitsu Makoto, Kawamura Koji, Kawata Takahito, Kishimoto Kenji, Tatara Raine, Hagino Takeshi, Fujiwara Shin-Ichiro, Shimomura Yoshimitsu, Sakaguchi Hirotoshi, Hirabayashi Shigeki, Ishii Hiroto, Onda Yoshiyuki, Kato Itaru, Kawajiri Akihisa, Shindo Takero, Tokunaga Masahito, Nonami Atsushi, Muranushi Hiroyuki, Yoshinaga Noriyoshi, Kawashima Naomi, Shiratori Souichi, Tada Yuma, Tanoue Sus-Umu, Hirayama Masahiro, Fukunaga Keiko, Ohbiki Marie

    BONE MARROW TRANSPLANTATION   Vol. 54 ( 7 ) page: 1004 - 1012   2019.7

  101. 【細胞治療の新時代】骨髄由来間葉系幹細胞 Reviewed

    村田 誠

    日本内科学会雑誌   Vol. 108 ( 7 ) page: 1369 - 1374   2019.7

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  102. HLA discrepancy between graft and host rather than that graft and first donor impact the second transplant outcome. Reviewed International journal

    Yoshinobu Maeda, Tomotaka Ugai, Eisei Kondo, Kazuhiro Ikegame, Makoto Murata, Naoyuki Uchida, Toshihiro Miyamoto, Satoshi Takahashi, Kazuteru Ohashi, Hirohisa Nakamae, Takahiro Fukuda, Makoto Onizuka, Tetsuya Eto, Shuichi Ota, Makoto Hirokawa, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshinobu Kanda, Junya Kanda

    Haematologica   Vol. 104 ( 5 ) page: 1055 - 1061   2019.5

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    Second allogeneic hematopoietic stem cell transplantation is a curative treatment option for patients with hematologic malignancies. However, it is unclear whether HLA discrepancy between graft and first donor has an impact on the outcome of second transplantation. We retrospectively analyzed 646 patients receiving second transplantation after an initial HLA mismatched transplantation. With regard to graft-versus-host, the one-allele mismatch (1 mismatch) group (SHR, 1.88; 95%CI: 0.79-4.45; P=0.163) and more than one-allele mismatch group (≥ 2 mismatch) (SHR, 1.84; 95%CI, 0.75-4.51; P=0.182) had higher risks of grade III-IV acute graft-versus-host disease (GvHD) compared to the HLA-matched (0 mismatch) group. In contrast, no difference in risk of acute GvHD was found among the 0, 1, and ≥ 2 mismatch group with respect to graft-versus-first donor. With regard to graft-versus-host, the ≥ 2 mismatch group showed a significantly higher risk of treatment-related mortality (SHR, 1.90; 95%CI, 1.04-3.50; P=0.038) compared to the 0 mismatch group, while the risk of relapse was slightly lower in the ≥ 2 mismatch group (SHR, 068; 95%CI, 0.44-1.06; P=0.086). In contrast, with regard to graft-versus-first donor, there were no significant differences in treatment-related mortality or relapse among the three groups. These findings suggested that HLA discrepancy between graft and host induces transplant-related immunological responses in second transplantation leading to an increase in treatment-related mortality, in contrast, the biological effects of HLA discrepancy between graft and first donor on outcome may be negligible.

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  103. Quantitative Assessment of T Cell Clonotypes in Human Acute Graft-versus-Host Disease Tissues. Reviewed International journal

    Daisuke Koyama, Makoto Murata, Ryo Hanajiri, Tomohiro Akashi, Shingo Okuno, Sonoko Kamoshita, Jakrawadee Julamanee, Erina Takagi, Kotaro Miyao, Reona Sakemura, Tatsunori Goto, Seitaro Terakura, Tetsuya Nishida, Hitoshi Kiyoi

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   Vol. 25 ( 3 ) page: 417 - 423   2019.3

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    Owing to the difficulty in isolating T cells from human biopsy samples, the characteristics of T cells that are infiltratinghuman acute graft-versus-host disease (GVHD) tissues remain largely uninvestigated. In the present study, TCR-β deep sequencing of various GVHD tissue samples and concurrent peripheral blood obtained from transplant recipients was performed in combination with functional assays of tissue-infiltrating T cell clones. The T cell repertoire was more skewed in GVHD tissues than in the peripheral blood. The frequent clonotypes differed from tissue to tissue in the same patient, and the frequent clonotypes in the same tissue differed from patient to patient. Two T cell clones were successfully isolated from GVHD skin of a patient. In a cytotoxicity assay, both Tcell clones lysed patient peripheral blood mononuclear cells, but not donor-derived Epstein-Barr virus-transformed lymphoblastoid cells. Their clonotypes were identical to the most and second most frequent T cell clonotypes in the original GVHD skin and accounted for almost all of the skin-infiltrating T cells. These results suggest that human acute GVHD may result from only a few different alloreactive cytotoxic T cell clones, which differ from tissue to tissue and from patient to patient. The characterization of T cells infiltrating human GVHD tissues should be further investigated.

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  104. Clinical Implications of t(11;14) in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation. Reviewed International journal

    Hiroyuki Takamatsu, Takeshi Yamashita, Shingo Kurahashi, Takayuki Saitoh, Tadakazu Kondo, Takeshi Maeda, Hideyuki Nakazawa, Makoto Murata, Tomoko Narita, Junya Kuroda, Hisako Hashimoto, Koji Kawamura, Toshihiro Miyamoto, Sumihisa Honda, Tatsuo Ichinohe, Yoshiko Atsuta, Kazutaka Sunami

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   Vol. 25 ( 3 ) page: 474 - 479   2019.3

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    Conventional cytogenetic analyses and fluorescent in situ hybridization (FISH) are helpful for stratifying patients with multiple myeloma (MM) into high-risk [t(4;14), t(14;16), and/or del 17p] and standard-risk [t(11;14)] categories. However, the prognosis of patients with MM treated with autologous stem cell transplantation (ASCT) stratified according to these categories remains unclear. This retrospective observational study analyzed 97 patients with MM who received a single, planned ASCT after treatment with 200 mg/m2 melphalan between 2001 and 2011. The patients were grouped according to chromosomal abnormality, including t(11;14) (n = 45), t(4;14) (n = 31), del 17p (n = 10), t(11;14) with del 17p (n = 7), and t(4;14) with del 17p (n = 4). Median overall survival (OS) of the t(11;14) group (64.1 months) was not significantly different from that of the t(4;14) group (not reached), but it was significantly longer than that of the del 17p group (23.0 months; P = .002). G-banding revealed that the median OS of the t(11;14) group with additional chromosomal abnormalities (ACAs) (46.2 months) was significantly shorter than that of the t(11;14) group without ACAs (not reached; P = .005) and the t(4;14) group (not reached; P = .010). These findings highlight the importance of G-banding in patients with t(11;14) MM.

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  105. 用語解説 HLAハプロタイプ Reviewed

    村田 誠

    再生医療   Vol. 18 ( 1 ) page: 51 - 52   2019.2

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  106. Impacts of thymoglobulin in patients with acute leukemia in remission undergoing allogeneic HSCT from different donors. Reviewed International journal

    Manabu Wakamatsu, Seitaro Terakura, Kazuteru Ohashi, Takahiro Fukuda, Yukiyasu Ozawa, Heiwa Kanamori, Masashi Sawa, Naoyuki Uchida, Shuichi Ota, Akiko Matsushita, Yoshinobu Kanda, Hirohisa Nakamae, Tatsuo Ichinohe, Koji Kato, Makoto Murata, Yoshiko Atsuta, Takanori Teshima

    Blood advances   Vol. 3 ( 2 ) page: 105 - 115   2019.1

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    Antithymocyte globulin (ATG) is widely used to reduce acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD). To clarify the different impacts of ATG for conditioning across different donor types, we retrospectively analyzed patients with acute leukemia (n = 6617) who underwent hematopoietic stem cell transplantation between 2008 and 2015 with ATG (n = 279) or without ATG (n = 6338). Because thymoglobulin is the only ATG drug approved for GVHD prophylaxis in Japan since September 2008, we included thymoglobulin alone in the present analysis. The survivors' median follow-up time was 1081 days. Patients were categorized into 5 groups: cord blood (CB; n = 1915), matched related donor (n = 1772), 1-antigen mismatched related donor (1-MMRD; n = 225), matched unrelated donor (MUD; n = 1742), and 1-allele mismatched unrelated donor (1-MMUD; n = 963). In multivariate analysis, ATG decreased overall survival (hazard ratio [HR], 1.403; P = .054) and GVHD-free/relapse-free survival (GRFS) (HR, 1.458; P = .053) in association with increased nonrelapse mortality (NRM) (HR, 1.608; P =03) with CB, whereas it improved GRFS (HR, 0.515; P < .01) and decreased grades II to IV aGVHD (HR, 0.576; P < .01), extensive cGVHD (HR, 0.460; P = .02), and NRM (HR, 0.545; P = .03) with 1-MMUD. ATG did not impact survival with 1-MMRD and MUD. The use of ATG in conditioning is beneficial due to the reduction in acute/chronic GVHD without increasing NRM or disease relapse only in 1-MMUD transplantation. On the other hand, ATG is not recommended for CB transplantation.

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  107. Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia. Reviewed International journal

    Motohiro Kato, Mio Kurata, Junya Kanda, Koji Kato, Daisuke Tomizawa, Kazuko Kudo, Nao Yoshida, Kenichiro Watanabe, Hiroyuki Shimada, Jiro Inagaki, Katsuyoshi Koh, Hiroaki Goto, Keisuke Kato, Yuko Cho, Yuki Yuza, Atsushi Ogawa, Keiko Okada, Masami Inoue, Yoshiko Hashii, Takanori Teshima, Makoto Murata, Yoshiko Atsuta

    Bone marrow transplantation   Vol. 54 ( 1 ) page: 68 - 75   2019.1

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    Graft-versus-host disease (GVHD) occasionally leads to morbidity and mortality but is thought to reduce the risk of relapses in patients with a hematological malignancy. However, information on the effect of GVHD in pediatric leukemia is limited. Using a nationwide registry, we retrospectively analyzed 1526 children who underwent allogeneic stem cell transplantation for leukemia. Grades 0-I acute GVHD were associated with a higher relapse rate at three years after transplantation, at 25.4 and 24.3%, respectively, than grades II, III, or IV acute GVHD at 18.9%, 21.2%, and 2.6%, respectively. In contrast, the overall survival curve of the grades 0 and I GVHD groups (79.0% and 79.5%, respectively) approximated that of the grade II GVHD group (76.3%), and the probability of survival was worst in the severe GVHD groups (66.9% for grade III and 42.5% for grade IV). Chronic GVHD also reduced the relapse risk but conferred no survival advantage. Acute lymphoblastic leukemia was more sensitive to acute GVHD than acute myeloid leukemia (AML) while AML was more sensitive to chronic GVHD. Our study reproduced the preventive effects of GVHD against pediatric leukemia relapses but failed to demonstrate a significant survival advantage.

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  108. 【白血病UPDATE】白血病各論 急性リンパ性白血病に対する抗体医薬の臨床効果 ブリナツモマブ、イノツズマブ・オゾガマイシン、リツキシマブ Reviewed

    村田 誠

    医学のあゆみ   Vol. 268 ( 1 ) page: 49 - 53   2019.1

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    近年、急性リンパ性白血病(ALL)に対する抗体医薬の開発が進んでおり、なかでもブリナツモマブ、イノツズマブ・オゾガマイシン(InO)、リツキシマブの臨床効果が明らかにされつつある。ブリナツモマブは抗CD19抗体と抗CD3抗体のキメラ蛋白である。再発または難治性フィラデルフィア染色体(Ph)陰性B細胞ALL(B-ALL)に対する臨床第III相試験で、化学療法と比べて高い寛解導入成功率と50%生存期間の延長を認めた。ただし、副作用として中枢神経系イベントが発生しうる。InOは抗CD22抗体に細胞傷害活性化合物カリケアマイシンを抱合させたものである。InOも再発または難治性のPh陰性B-ALLに対する第III相試験で、化学療法と比べて高い寛解導入成功率と生存期間の延長が示されている。ただし、副作用として肝中心静脈閉塞症(VOD)が懸念される。リツキシマブは、新規発症のCD20陽性Ph陰性B-ALLに対する多剤併用化学療法にリツキシマブ併用または非併用に割り付ける第III相試験において、非再発生存率が併用群で勝ることが確認された。今後は各抗体医薬の使い分け、あるいはそれらの組合せ、また化学療法や造血幹細胞移植との組合せ方などについて最適化していく必要がある。(著者抄録)

  109. Introduction of Genetically Modified CD3ζ Improves Proliferation and Persistence of Antigen-Specific CTLs. Reviewed International journal

    Kotaro Miyao, Seitaro Terakura, Shingo Okuno, Jakrawadee Julamanee, Keisuke Watanabe, Hiroshi Hamana, Hiroyuki Kishi, Reona Sakemura, Daisuke Koyama, Tatsunori Goto, Tetsuya Nishida, Makoto Murata, Hitoshi Kiyoi

    Cancer immunology research   Vol. 6 ( 6 ) page: 733 - 744   2018.6

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    The clinical efficacy of T-cell therapies based on T cells transduced with genes encoding tumor-specific T-cell receptors (TCR-T) is related to the in vivo persistence of the T cells. To improve persistence without modifying TCR affinity, we instead modified intracellular signaling, using artificial T cell-activating adapter molecules (ATAM), generated by inserting the intracellular domain (ICD) of activating T-cell signaling moieties into CD3ζ. ATAMs with the ICD of either CD28 or 4-1BB were generated, assembled into the TCR complex as a part of CD3ζ, and enhanced downstream signaling from the supramolecular activation cluster. ATAMs were retrovirally introduced into human CMV-specific or NY-ESO-1-specific TCR-transduced CD8+ T lymphocytes, and downstream functionality was then examined. ATAM-transduced NY-ESO-1 TCR-T cells were also investigated using the U266-xenograft mouse model. ATAMs were successfully transduced and localized to the cell membrane. ATAM-transduced CMV-specific T cells retained their cytotoxic activity and cytokine production against peptide-pulsed target cells without altering antigen-specificity and showed resistance to activation-induced cell death. Upon both single and repeated stimulation, CD3ζ/4-1BB-transduced T cells had superior proliferation to the CD3ζ-transduced T cells in both the CMV-specific and the NY-ESO-1 TCR-T models and significantly improved antitumor activity compared with untransduced T cells both in vitro and in a mouse xenograft model. ATAM-transduced TCR-T cells demonstrated improved proliferation and persistence in vitro and in vivo This strategy to control the intracellular signaling of TCR-T cells by ATAM transduction in combination with various tumor-specific TCRs may improve the efficacy of TCR-T therapy. Cancer Immunol Res; 6(6); 733-44. ©2018 AACR.

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  110. 【臨床血液学-最新情報と今後の展望2018(造血幹細胞移植(がん免疫含む))-】急性GVHDの診断と治療 Reviewed

    村田 誠

    臨床血液   Vol. 59 ( 5 ) page: 540 - 548   2018.5

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    急性移植片対宿主病(GVHD)は、皮膚、肝、消化管の少なくとも一臓器に障害が存在し、かつGVHD類似の他の疾患が否定される場合に診断される。上部消化管GVHDを除き、急性GVHDは臨床診断で行われる。生検による病理診断は必ずしも臨床診断と一致しない。各臓器stageをもとに全身gradeを判定するが、その重症度分類は治療反応性や予後を正確に反映している訳ではない。その不完全ともいえる重症度分類を補うべく、GVHDバイオマーカーの同定が精力的に進められている。治療反応性や予後を正確に反映する重症度分類を確立することができれば、急性GVHDの治療を層別化治療へと進化させる可能性がある。(著者抄録)

  111. Phase I study of cord blood transplantation with intrabone marrow injection of mesenchymal stem cells: A clinical study protocol. Reviewed International journal

    Tatsunori Goto, Makoto Murata, Seitaro Terakura, Tetsuya Nishida, Yoshiya Adachi, Yoko Ushijima, Kazuyuki Shimada, Yuichi Ishikawa, Fumihiko Hayakawa, Nobuhiro Nishio, Satoshi Nishiwaki, Akihiro Hirakawa, Katsuyoshi Kato, Yoshiyuki Takahashi, Hitoshi Kiyoi

    Medicine   Vol. 97 ( 17 ) page: e0449   2018.4

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    INTRODUCTION: Delayed hematological recovery, graft failure, and acute graft-versus-host disease (GVHD) still remain major problems in cord blood transplantation (CBT). Mesenchymal stem cells (MSCs) are known to support bone marrow stroma and promote hematopoiesis. Additionally, MSCs possess immunomodulatory properties and are used clinically for the treatment of acute GVHD. Therefore, the use of MSCs to enhance engraftment and prevent GVHD after allogeneic hematopoietic cell transplantation has been explored. Recent clinical trials have shown the feasibility and safety of intravenous cotransplantation of MSCs with cord blood cells in pediatric patients, but not in adult patients, who are at greater risk of graft failure. As for the route of administration of MSCs, direct intrabone marrow injection of MSCs is thought to enhance the engraftment of cord blood cells more than intravenous injection. Based on these background findings, this clinical trial was designed to develop a new strategy to enhance engraftment and prevent GVHD after CBT. METHODS AND ANALYSIS: This is a single-center, phase I, clinical study to evaluate the safety of CBT combined with intrabone marrow injection of ex vivo expanded MSCs from bone marrow of a third-party donor. Adult patients with hematological disorders are eligible for this study. The target sample size is 5, and the registration period is 3 years. The target dose of MSCs infused is 0.5 × 10 cells/kg of patient body weight. On the day of CBT, MSCs are injected into the intrabone marrow of the patient 4 hours before the infusion of a single cord blood unit. The conditioning regimen varies according to patient age and disease. GVHD prophylaxis consists of a combination of tacrolimus and methotrexate. The primary endpoint of this study is infusional toxicity of MSCs within 14 days after transplantation.

    DOI: 10.1097/MD.0000000000010449

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  112. [MonoMAC syndrome patient developing myelodysplastic syndrome following persistent EBV infection]. Reviewed International journal

    Yamamoto H, Hattori H, Takagi E, Morishita T, Ishikawa Y, Terakura S, Nishida T, Ito Y, Murata M, Kiyoi H

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 59 ( 3 ) page: 315 - 322   2018.3

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    DOI: 10.11406/rinketsu.59.315

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  113. [Mesenchymal stem cell therapy in hematopoietic stem cell transplantation]. Reviewed International journal

    Goto T, Murata M

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 59 ( 2 ) page: 195 - 204   2018.2

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    DOI: 10.11406/rinketsu.59.195

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  114. 【癌治療のパラダイムシフトがもたらした免疫反応の新知見】CAR(キメラ抗原受容体)-T細胞療法 Reviewed

    村田 誠

    臨床免疫・アレルギー科   Vol. 69 ( 2 ) page: 148 - 153   2018.2

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  115. Intrabone single unit cord blood transplantation for hematological malignancies

    Murata Makoto, Maeda Yoshinobu, Masuko Masayoshi, Fukuhara Noriko, Nishida Tetsuya, Terakura Seitaro, Ishikawa Yuichi, Tanimoto Mitsune, Shibasaki Yasuhiko, Suzuki Ritsuro, Kodera Yoshihisa, Kiyoi Hitoshi, Naoe Tomoki

    CANCER SCIENCE   Vol. 109   page: 757 - 757   2018.1

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  116. [Acute graft-versus-host disease: diagnosis and treatment].

    Murata M

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 59 ( 5 ) page: 540-548   2018

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    DOI: 10.11406/rinketsu.59.540

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  117. 再発・難治性ALLに対する抗CD19-BiTE®抗体開発の現状 Invited Reviewed

    村田誠

    血液内科   Vol. 77 ( 2 ) page: 197 - 202   2018

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  118. Efficacy and safety of autologous peripheral blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: A study protocol for a multicenter exploratory prospective study (Auto-Ph17 study). Reviewed International journal

    Satoshi Nishiwaki, Isamu Sugiura, Yasuhiko Miyata, Shigeki Saito, Masashi Sawa, Tetsuya Nishida, Koichi Miyamura, Yachiyo Kuwatsuka, Akio Kohno, Masaaki Yuge, Masanobu Kasai, Hiroatsu Iida, Shingo Kurahashi, Masahide Osaki, Tatsunori Goto, Seitaro Terakura, Makoto Murata, Hiroyoshi Nishikawa, Hitoshi Kiyoi

    Medicine   Vol. 96 ( 52 ) page: e9568   2017.12

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    INTRODUCTION: The prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) has been dramatically improved since the introduction of tyrosine kinase inhibitors (TKIs). Although allogeneic hematopoietic cell transplantation (allo-HCT) is a major treatment option, the role of autologous peripheral blood stem cell transplantation (auto-PBSCT) has been reconsidered, especially in patients who achieved early molecular remission. METHODS AND ANALYSIS: This is a multicenter exploratory study for Ph + ALL patients aged between 55 and 70 years who achieved complete molecular remission within 3 cycles of chemotherapy. The target sample size is 5, and the registration period is 2 years. The primary endpoint is Day100- mortality after transplantation, and the secondary endpoints are survival, relapse rate, nonrelapse mortality, and adverse events.This study is divided into 3 phases: peripheral blood stem cell harvest, transplantation, and maintenance. Chemomobilization is performed using a combination of cyclophosphamide (CPM), doxorubicin, vincristine (VCR), and prednisolone (PSL). As a preparative regimen, the LEED regimen is used, which consists of melphalan, CPM, etoposide, and dexamethasone. Twelve cycles of maintenance therapy using a combination of VCR, PSL, and dasatinib are performed.In association with relapse, the minimal residual disease (MRD) of BCR-ABL chimeric gene and T-cell subsets are analyzed both before and after auto-PBSCT. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board of Nagoya University Hospital and all the participating hospitals. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. TRIAL REGISTRATION: Trial registration number UMIN000026445.

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  119. Safety and persistence of WT1-specific T-cell receptor gene-transduced lymphocytes in patients with AML and MDS Reviewed International journal

    Isao Tawara, Shinichi Kageyama, Yoshihiro Miyahara, Hiroshi Fujiwara, Tetsuya Nishida, Yoshiki Akatsuka, Hiroaki Ikeda, Kazushi Tanimoto, Seitaro Terakura, Makoto Murata, Yoko Inaguma, Masahiro Masuya, Naoki Inoue, Tomohide Kidokoro, Sachiko Okamoto, Daisuke Tomura, Hideto Chono, Ikuei Nukaya, Junichi Mineno, Tomoki Naoe, Nobuhiko Emi, Masaki Yasukawa, Naoyuki Katayama, Hiroshi Shiku

    BLOOD   Vol. 130 ( 18 ) page: 1985 - 1994   2017.11

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    Wilms' tumor 1 (WT1) is constantly expressed in leukemic cells of acute leukemia and myelodysplastic syndrome (MDS). A T-cell receptor (TCR) that specifically reacts with WT1 peptide in the context of HLA-A*24:02 has been identified. We conducted a first-inhuman trial of TCR-gene transduced T-cell (TCR-T-cell) transfer in patients with refractory acute myeloblastic leukemia (AML) and high-risk MDS to investigate the safety and cell kinetics of the T cells. The WT1-specific TCR-gene was transduced to T cells using a retroviral vector encoding small interfering RNAs for endogenous TCR genes. The T cells were transferred twice with a 4-week interval in a dose-escalating design. After the second transfer, sequential WT1 peptide vaccines were given. Eight patients, divided into 2 dose cohorts, received cell transfer. No adverse events of normal tissue were seen. The TCR-T cells were detected in peripheral blood for 8 weeks at levels proportional to the dose administered, and in 5 patients, they persisted throughout the study period. The persisting cells maintained ex vivo peptide-specific immune reactivity. Two patients showed transient decreases in blast counts in bone marrow, which was associated with recovery of hematopoiesis. Four of 5 patients who had persistent T cells at the end of the study survived more than 12 months. These results suggest WT1-specific TCR-T cells manipulated by ex vivo culture of polyclonal peripheral lymphocytes survived in vivo and retained the capacity to mount an immune reaction to WT1.

    DOI: 10.1182/blood-2017-06-791202

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  120. Impact of the presence of HLA 1-locus mismatch and the use of low-dose antithymocyte globulin in unrelated bone marrow transplantation Reviewed International journal

    K. Kawamura, J. Kanda, S. Fuji, M. Murata, K. Ikegame, K. Yoshioka, T. Fukuda, Y. Ozawa, N. Uchida, K. Iwato, T. Sakura, M. Hidaka, H. Hashimoto, T. Ichinohe, Y. Atsuta, Y. Kanda

    BONE MARROW TRANSPLANTATION   Vol. 52 ( 10 ) page: 1390 - 1398   2017.10

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    HLA 1-locus-mismatched unrelated donors (1MMUD) have been used in allogeneic hematopoietic stem cell transplantation (allo-HCT) for patients who lack an HLA-matched donor. We retrospectively analyzed 3313 patients with acute leukemia or myelodysplastic syndrome who underwent bone marrow transplantation from an HLA allele-matched unrelated donor (MUD) or 1MMUD between 2009 and 2014. We compared the outcomes of MUD (n = 2089) and 1MMUD with antithymocyte globulin (ATG) (1MM-ATG(+); n= 109) with those of 1MMUD without ATG (1MM-ATG(-); n = 1115). The median total dose of ATG (thymoglobulin) was 2.5 mg/kg (range 1.0-11.0 mg/kg) in the 1MM-ATG(+) group. The rates of grade III-IV acute GvHD, non-relapse mortality (NRM) and overall mortality were significantly lower in the MUD group than in the 1MM-ATG(-) group (hazard ratio (HR) 0.77, P = 0.016; HR 0.74; P &lt; 0.001; and HR 0.87, P = 0.020, respectively). Likewise, the rates of grade III-IV acute GVHD, NRM and overall mortality were significantly lower in the 1MM-ATG(+) group than in the 1MM-ATG(-) group (HR 0.42, P = 0.035; HR 0.35, P &lt; 0.001; and HR 0.71, P = 0.042, respectively). The outcome of allo-HCT from 1MM-ATG(-) was inferior to that of allo-HCT from MUD even in the recent cohort. However, the negative impact of 1MMUD disappeared with the use of low-dose ATG without increasing the risk of relapse.

    DOI: 10.1038/bmt.2017.153

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  121. High incidence of extensive chronic graft-versus-host disease in patients with the REG3A rs7588571 non-GG genotype. Reviewed International journal

    Daisuke Koyama, Makoto Murata, Ryo Hanajiri, Shingo Okuno, Sonoko Kamoshita, Jakrawadee Julamanee, Erina Takagi, Daiki Hirano, Kotaro Miyao, Reona Sakemura, Tatsunori Goto, Fumihiko Hayakawa, Aika Seto, Yukiyasu Ozawa, Koichi Miyamura, Seitaro Terakura, Tetsuya Nishida, Hitoshi Kiyoi

    PloS one   Vol. 12 ( 9 ) page: e0185213   2017.9

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    Regenerating islet-derived protein 3 alpha (REG3A) is a biomarker of lower gastrointestinal graft-versus-host disease (GVHD); however, the biological role of REG3A in the pathophysiology of GVHD is not understood. Here, we examined the association between a single nucleotide polymorphism in the REG3A gene, rs7588571, which is located upstream and within 2 kb of the REG3A gene, and transplant outcomes including the incidence of GVHD. The study population consisted of 126 adult Japanese patients who had undergone bone marrow transplantation from a HLA-matched sibling. There was no association between rs7588571 polymorphism and the incidence of acute GVHD. However, a significantly higher incidence of extensive chronic GVHD was observed in patients with the rs7588571 non-GG genotype than in those with the GG genotype (Odds ratio 2.6; 95% confidence interval, 1.1-6.0; P = 0.029). Semi-quantitative reverse transcription PCR demonstrated that the rs7588571 non-GG genotype exhibited a significantly lower REG3A mRNA expression level than the GG genotype (P = 0.032), and Western blot analysis demonstrated that the rs7588571 non-GG genotype exhibited a trend toward lower REG3A protein expression level than the GG genotype (P = 0.053). Since REG proteins have several activities that function to control intestinal microbiota, and since intestinal dysbiosis is in part responsible for the development of GVHD, our findings lead to the novel concept that REG3A could have some protective effect in the pathogenesis of GVHD through the regulation of gut microbiota.

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  122. Erratum: High-dose chemotherapy with autologous peripheral blood stem cell transplantation for choriocarcinoma: A case report and literature review. Reviewed International journal

    Eiko Yamamoto, Kaoru Niimi, Kayo Fujikake, Tetsuya Nishida, Makoto Murata, Ayako Mitsuma, Yuichi Ando, Fumitaka Kikkawa

    Molecular and clinical oncology   Vol. 7 ( 3 ) page: 510 - 510   2017.9

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    [This corrects the article DOI: 10.3892/mco.2016.1011.].

    DOI: 10.3892/mco.2017.1315

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  123. GvHD prophylaxis after single-unit reduced intensity conditioning cord blood transplantation in adults with acute leukemia Reviewed International journal

    S. Terakura, Y. Kuwatsuka, S. Yamasaki, A. Wake, J. Kanda, Y. Inamoto, S. Mizuta, T. Yamaguchi, N. Uchida, Y. Kouzai, N. Aotsuka, H. Ogawa, H. Kanamori, K. Nishiwaki, S. Miyakoshi, M. Onizuka, I. Amano, T. Fukuda, T. Ichinohe, Y. Atsuta, M. Murata, T. Teshima

    BONE MARROW TRANSPLANTATION   Vol. 52 ( 9 ) page: 1261 - 1267   2017.9

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    To investigate better GVHD prophylaxis in reduced intensity conditioning umbilical cord blood transplantation (RIC-UCBT), we compared transplant outcomes after UCBT among GvHD prophylaxes using the registry data. We selected patients transplanted for AML or ALL with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 748 first RIC-UCBT between 2000 and 2012 (MTX+ group, 446, MMF+ group, 302) were included. The cumulative incidence of neutrophil and platelet counts higher than 50 000/mu L was significantly better in the MMF+ group (relative risk (RR), 1.55; P &lt; 0.001: RR, 1.34; P = 0.003, respectively). In multivariate analyses, the risk of grade II-IV and III-IV acute GvHD was significantly higher in the MMF+ group than in the MTX+ group (RR, 1.75; P &lt; 0.001: RR, 1.97; P = 0.004, respectively). In disease-specific analyses of AML, the risk of relapse of high-risk disease was significantly lower in the MMF+ group (RR, 0.69; P = 0.009), whereas no significant difference was observed in the risk of relapse-free and overall survival in high-risk disease. In patients with standard-risk disease, no significant differences were noted in the risk of relapse or survival between the MTX+ and MMF+ groups. Collectively, these results suggest that MMF-containing prophylaxis may be preferable in RIC-UCBT, particularly for high-risk disease.

    DOI: 10.1038/bmt.2017.116

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  124. ステロイド:抗炎症作用と免疫抑制作用の発現機序 Invited

    村田 誠

    臨床麻酔   Vol. 41 ( 9 ) page: 1206 - 1212   2017.9

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  125. Phase II study of intrabone single unit cord blood transplantation for hematological malignancies. Reviewed International journal

    Makoto Murata, Yoshinobu Maeda, Masayoshi Masuko, Yasushi Onishi, Tomoyuki Endo, Seitaro Terakura, Yuichi Ishikawa, Chisako Iriyama, Yoko Ushijima, Tatsunori Goto, Nobuharu Fujii, Mitsune Tanimoto, Hironori Kobayashi, Yasuhiko Shibasaki, Noriko Fukuhara, Yoshihiro Inamoto, Ritsuro Suzuki, Yoshihisa Kodera, Tadashi Matsushita, Hitoshi Kiyoi, Tomoki Naoe, Tetsuya Nishida

    Cancer science   Vol. 108 ( 8 ) page: 1634 - 1639   2017.8

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    The outcomes of cord blood transplantation with non-irradiated reduced-intensity conditioning for hematological malignancies need to be improved because of graft failure and delayed engraftment. Intrabone infusion of cord blood cells has the potential to resolve the problems. In this phase II study, 21 adult patients with hematological malignancy received intrabone transplantation of serological HLA-A, B, and DR ≥4/6 matched single cord blood with a median number of cryopreserved total nucleated cells of 2.7 × 107 /kg (range, 2.0-4.9 × 107 /kg) following non-irradiated fludarabine-based reduced-intensity conditioning. Short-term methotrexate and tacrolimus were given as graft-versus-host disease prophylaxis, and granulocyte colony-stimulating factor was given after transplantation. No severe adverse events related to intrabone injection were observed. The cumulative incidences of neutrophils ≥0.5 × 109 /L, reticulocytes ≥1%, and platelets ≥20 × 109 /L recoveries were 76.2%, 71.4%, and 76.2%, respectively, with median time to recoveries of 17, 28, and 32 days after transplantation, respectively. The probability of survival with neutrophil engraftment on day 60 was 71.4%, and overall survival at 1 year after transplantation was 52.4%. The incidences of grade II-IV and III-IV acute graft-versus-host disease were 44% and 19%, respectively, with no cases of chronic graft-versus-host disease. The present study showed the safety of direct intrabone infusion of cord blood. Further analysis is required to confirm the efficacy of intrabone single cord blood transplantation with non-irradiated reduced-intensity conditioning for adult patients with hematological malignancy. This study was registered with UMIN-CTR, number 000000865.

    DOI: 10.1111/cas.13291

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  126. 後天性慢性赤芽球癆に対するABO血液型一致同胞間骨髄移植後も赤血球造血のみ遅延した1例 Reviewed

    西田 徹也, 今橋 真弓, 今橋 伸彦, 大橋 春彦, 勝見 章, 寺倉 精太郎, 村田 誠, 清井 仁, 直江 知樹

    日本輸血細胞治療学会誌   Vol. 63 ( 4 ) page: 614 - 618   2017.8

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    後天性慢性赤芽球癆の多くは自己免疫的機序が関与しており、免疫抑制療法が有効であるが、難治例や再発例に対する治療は難渋することがある。今回、後天性慢性赤芽球癆に対してHLA一致同胞間骨髄移植を行った。症例は36歳、女性。びまん性全身性強皮症を合併した赤芽球癆と診断され、シクロスポリンによる治療が無効であったため、HLA一致およびABO血液型一致の実妹より骨髄移植を施行した。移植後の好中球と血小板の回復は速やかであったが、赤血球造血のみ遅延し、移植後2ヵ月以上も網状赤血球は回復せず、赤血球輸血依存の状態が続いた。末梢血T細胞は、移植後50日以上ドナー由来60〜70%と混合キメラが持続したため、day64とday85にドナーCD3陽性T細胞をそれぞれ1.10×10^7/kg、3.30×10^7/kg輸注した。その後、ドナーキメリズム回復とともに赤血球造血回復も得られた。難治性赤芽球癆に対して同種骨髄移植は有効ではあるが、ドナー完全キメラ達成が赤芽球癆の治癒に重要である。(著者抄録)

    DOI: 10.3925/jjtc.63.614

  127. Impact of graft-versus-host disease on outcomes after pediatric single cord blood transplantation: a retrospective analysis from the JSHCT GVHD Working Group

    Kanda J., Umeda K., Kato K., Murata M., Sugita J., Adachi S., Koh K., Inagaki J., Goto H., Yoshida N., Yasui M., Koga Y., Hori T., Inoue M., Hashii Y., Atsuta Y., Teshima T.

    BONE MARROW TRANSPLANTATION   Vol. 52   page: S54 - S54   2017.7

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  128. Autologous hematopoietic cell transplantation for acute promyelocytic leukemia in second complete remission: outcomes before and after the introduction of arsenic trioxide. Reviewed International journal

    Masamitsu Yanada, Shingo Yano, Heiwa Kanamori, Moritaka Gotoh, Nobuhiko Emi, Kyoko Watakabe, Mineo Kurokawa, Akinori Nishikawa, Takehiko Mori, Naoto Tomita, Makoto Murata, Hisako Hashimoto, Hideho Henzan, Yoshinobu Kanda, Masashi Sawa, Akio Kohno, Yoshiko Atsuta, Tatsuo Ichinohe, Akiyoshi Takami

    Leukemia & lymphoma   Vol. 58 ( 5 ) page: 1061 - 1067   2017.5

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    We conducted a retrospective registry-based study involving 198 patients with acute promyelocytic leukemia (APL) who underwent autologous hematopoietic cell transplantation (HCT) during second complete remission (CR2) from 1995 to 2012. Arsenic trioxide (ATO) became commercially available in Japan in December 2004, and a substantial increase in the annual numbers of transplantations has occurred since 2005. Patients transplanted after 2006 had significantly better relapse-free and overall survival than those transplanted before 2004 (p = .028 and p = .027, respectively). There was a significant difference in cumulative incidence of relapse in favor of those transplanted after 2006 (p = .008), whereas non-relapse mortality did not differ between the two groups (p = .683). Our findings suggest that the introduction of ATO may have reduced post-transplantation relapse without increasing non-relapse mortality, resulting in significant improvements in overall outcomes for relapsed APL patients undergoing autologous HCT during CR2.

    DOI: 10.1080/10428194.2016.1231406

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  129. Inotuzumab ozogamicinによる新たな急性リンパ性白血病治療 Invited

    村田 誠

    血液内科   Vol. 74 ( 5 ) page: 687 - 690   2017.5

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  130. Impact of T-cell chimerism on relapse after cord blood transplantation for hematological malignancies: Nagoya Blood and Marrow Transplantation Group study Reviewed International journal

    E. Yokohata, Y. Kuwatsuka, H. Ohashi, S. Terakura, N. Kawashima, A. Seto, S. Kurahashi, Y. Ozawa, T. Goto, N. Imahashi, T. Nishida, K. Miyao, R. Sakemura, T. Kato, M. Sawa, A. Kohno, H. Sao, H. Iida, H. Kiyoi, T. Naoe, K. Miyamura, M. Murata

    BONE MARROW TRANSPLANTATION   Vol. 52 ( 4 ) page: 612 - 614   2017.4

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    DOI: 10.1038/bmt.2016.323

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  131. Exploratory research for optimal GvHD prophylaxis after single unit CBT in adults: short-term methotrexate reduced the incidence of severe GvHD more than mycophenolate mofetil Reviewed International journal

    S. Terakura, A. Wake, Y. Inamoto, M. Murata, R. Sakai, T. Yamaguchi, S. Takahashi, N. Uchida, Y. Onishi, K. Ohashi, Y. Ozawa, H. Kanamori, H. Yamaguchi, T. Fukuda, T. Ichinohe, M. Takanashi, Y. Atsuta, T. Teshima

    BONE MARROW TRANSPLANTATION   Vol. 52 ( 3 ) page: 423 - 430   2017.3

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    In order to examine GvHD prophylaxis in umbilical cord blood transplantation (UCBT) in more detail, we compared transplant outcomes after UCBT for acute leukemia among GvHD prophylaxes using registry data. We selected patients transplanted with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 1516 first myeloablative UCBT between 2000 and 2012 (Cyclosporine A (CyA) plus MTX, 824, Tacrolimus (Tac) plus MTX, 554, Tac plus MMF, 138) were included. With adjusted analyses, Tac plus MMF showed a significantly higher risk for grade II-IV and III-IV acute GvHD than CyA or Tac plus MTX. Although NRM was similar, Tac plus MMF showed a significantly lower risk of relapse than CyA or Tac plus MTX. A significant difference was observed in the risk of overall mortality (OM) between the MTX-containing group and MMF-containing group. In patients with standard-risk disease, there was no significant difference in the risk of OM in any GvHD prophylaxis. However, in patients with advanced-risk disease, Tac plus MMF showed a significantly lower risk of OM. Therefore, MTX-containing prophylaxis is preferred in UCBT for standard-risk disease, whereas MMF-containing prophylaxis is preferred for advanced-risk disease. A prospective study to identify optimal GvHD prophylaxis for UCBT is warranted.

    DOI: 10.1038/bmt.2016.255

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  132. Impact of graft-versus-host disease on outcomes after unrelated cord blood transplantation Reviewed International journal

    J. Kanda, Y. Morishima, S. Terakura, A. Wake, N. Uchida, S. Takahashi, Y. Ono, Y. Onishi, H. Kanamori, N. Aotsuka, Y. Ozawa, H. Ogawa, T. Sakura, K. Ohashi, T. Ichinohe, K. Kato, Y. Atsuta, T. Teshima, M. Murata

    LEUKEMIA   Vol. 31 ( 3 ) page: 663 - 668   2017.3

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    The effect of graft-versus-host disease (GVHD) on transplant outcomes after unrelated cord blood transplantation (UCBT) has not been fully elucidated. We analyzed the impact of acute and chronic GVHD on outcomes in adult patients with acute leukemia or myelodysplastic syndrome who underwent their first UCBT (n= 2558). The effect of GVHD on outcomes was analyzed after adjusting for other significant variables. The occurrence of GVHD was treated as a time-dependent covariate. The occurrence of grade 1-2 or 3-4 acute GVHD was significantly associated with a lower relapse rate. Grade 3-4 acute GVHD was associated with a higher risk of non-relapse and overall mortality than no acute GVHD, whereas grade 1-2 acute GVHD was associated with a lower risk of non-relapse and overall mortality than no acute GVHD. Limited or extensive chronic GVHD was significantly associated with a lower relapse rate. Limited chronic GVHD was associated with a lower overall and non-relapse mortality than no chronic GVHD. In conclusion, mild acute or chronic GVHD was associated not only with a low risk of relapse but also with a low risk of non-relapse mortality, and provides a survival benefit in UCBT.

    DOI: 10.1038/leu.2016.288

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  133. Low-dose thymoglobulin as second-line treatment for steroid-resistant acute GvHD: An analysis of the JSHCT International journal

    M. Murata, K. Ikegame, Y. Morishita, H. Ogawa, K. Kaida, H. Nakamae, T. Ikeda, T. Nishida, M. Inoue, T. Eto, K. Kubo, T. Sakura, T. Mori, N. Uchida, T. Ashida, Y. Matsuhashi, Y. Miyazaki, T. Ichinohe, Y. Atsuta, T. Teshima

    Bone Marrow Transplantation   Vol. 52 ( 2 ) page: 252 - 257   2017.2

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    A nationwide retrospective study for the clinical outcomes of 99 patients who had received thymoglobulin at a median total dose of 2.5 mg/kg (range, 0.5-18.5 mg/kg) as a second-line treatment for steroid-resistant acute GvHD was conducted. Of the 92 evaluable patients, improvement (complete or partial response) was observed in 55 patients (60%). Multivariate analysis demonstrated that male sex and grade III and IV acute GvHD were associated with a lower improvement rate, whereas thymoglobulin dose (&lt
    2.0, 2.0-3.9 and ≥4.0 mg/kg) was NS. Factors associated with significantly higher nonrelapse mortality included higher patient age (≥50 years), grade IV acute GvHD, no improvement of GvHD and higher dose of thymoglobulin (hazard ratio, 2.55
    95% confidence interval, 1.34-4.85
    P=0.004 for 2.0-3.9 mg/kg group and 1.79
    0.91-3.55
    P=0.093 for ≥4.0 mg/kg group). Higher dose of thymoglobulin was associated with a higher incidence of bacterial infections, CMV antigenemia and any additional infection. Taken together, low-dose thymoglobulin at a median total dose of 2.5 mg/kg provides a comparable response rate to standard-dose thymoglobulin reported previously, and &lt
    2.0 mg/kg thymoglobulin is recommended in terms of the balance between efficacy and adverse effects.

    DOI: 10.1038/bmt.2016.247

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    Scopus

    PubMed

  134. ヒト組織からの初代細胞分離法シリーズ 造血幹細胞移植における幹細胞採取と移植成績 Reviewed

    村田 誠

    Organ Biology   Vol. 24 ( 1 ) page: 61 - 69   2017.1

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  135. Malignant lymphoma with cardiac involvement.

    Terakura S, Onji M, Iriyama C, Goto T, Ushijima Y, Shimada K, Ishikawa Y, Nishida T, Hayakawa F, Murata M, Kiyoi H

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 58 ( 3 ) page: 239-242   2017

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    DOI: 10.11406/rinketsu.58.239

    PubMed

  136. 心臓浸潤を認めた悪性リンパ腫 Reviewed

    寺倉精太郎, 隂地真晃, 入山智沙子, 後藤辰徳, 牛島洋子, 島田和之, 石川裕一, 西田徹也, 早川文彦, 村田誠, 清井仁

    臨床血液   Vol. 58 ( 3 ) page: 239 - 242   2017

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  137. 【白血病学(下)-最新の基礎、臨床研究-】白血病治療の副作用・合併症対策と支持療法 造血幹細胞移植の副作用と対策 移植後合併症の予防と管理 間葉系幹細胞を用いたGVHDの予防と治療 Reviewed

    村田 誠

    日本臨床   Vol. 74 ( 増刊10 白血病学(下) ) page: 359 - 364   2016.12

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  138. 【白血病学(下)-最新の基礎、臨床研究-】白血病治療の副作用・合併症対策と支持療法 造血幹細胞移植の副作用と対策 移植片対宿主病(GVHD)(病態、予防、治療) 急性GVHD Reviewed

    村田 誠

    日本臨床   Vol. 74 ( 増刊10 白血病学(下) ) page: 365 - 370   2016.12

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  139. High-dose chemotherapy with autologous peripheral blood stem cell transplantation for choriocarcinoma: A case report and literature review Reviewed

    Yamamoto Eiko, Niimi Kaoru, Fujikake Kayo, Nishida Tetsuya, Murata Makoto, Mitsuma Ayako, Ando Yuichi, Kikkawa Fumitaka

    MOLECULAR AND CLINICAL ONCOLOGY   Vol. 5 ( 5 ) page: 660 - 664   2016.11

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    DOI: 10.3892/mco.2016.1011

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  140. 私のこの一枚 目で見るGVL効果 Reviewed

    村田 誠

    血液フロンティア   Vol. 26 ( 12 ) page: 1629 - 1633   2016.11

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  141. 【造血器腫瘍のゲノム/エピゲノム解析研究と免疫/分子標的療法の進歩】急性リンパ性白血病におけるゲノム解析と免疫療法 Reviewed

    早川 文彦, 村田 誠

    血液内科   Vol. 73 ( 5 ) page: 592 - 597   2016.11

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  142. High-dose chemotherapy with autologous peripheral blood stem cell transplantation for choriocarcinoma: A case report and literature review. Reviewed International journal

    Eiko Yamamoto, Kaoru Niimi, Kayo Fujikake, Tetsuya Nishida, Makoto Murata, Ayako Mitsuma, Yuichi Ando, Fumitaka Kikkawa

    Molecular and clinical oncology   Vol. 5 ( 5 ) page: 660 - 664   2016.11

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    Choriocarcinoma is a malignant gestational trophoblastic neoplasia (GTN) and one of the curable types of gynecological cancer. However, 10% of choriocarcinoma patients have a poor prognosis, particularly when they have metastasis, apart from pulmonary metastasis, or do not go into remission by the second chemotherapeutic regimen. We herein present the case of a 36-year-old patient who had choriocarcinoma with metastases to the lungs, liver and kidneys. The 5th and 6th regimens with cisplatin for choriocarcinoma failed and the patient developed brain metastases. She was then treated with four cycles of high-dose ifosfamide, carboplatin and etoposide (ICE) with blood progenitor cell support after confirming the effectiveness of ICE at normal doses. The serum human chorionic gonadotropin (hCG) level was 140,009 mIU/ml at the start of high-dose ICE and the patient tolerated this regimen well. However, the beneficial effect was decreasing with each successive course of treatment, with the lowest level of hCG at 103 mIU/ml after the fourth course. The patient did not achieve complete remission and succumbed to the disease 4 months after the last chemotherapy. The findings of the present case and a review of the related literature suggest that high-dose ICE with stem cell rescue may be considered as a viable treatment option for a multi-drug resistant choriocarcinoma or GTN.

    PubMed

  143. Programmed Death-Ligand 1 on Antigen-presenting Cells Facilitates the Induction of Antigen-specific Cytotoxic T Lymphocytes: Application to Adoptive T-Cell Immunotherapy Reviewed

    Goto Tatsunori, Nishida Tetsuya, Takagi Erina, Miyao Kotaro, Koyama Daisuke, Sakemura Reona, Hanajiri Ryo, Watanabe Keisuke, Imahashi Nobuhiko, Terakura Seitaro, Murata Makoto, Kiyoi Hitoshi

    JOURNAL OF IMMUNOTHERAPY   Vol. 39 ( 8 ) page: 306 - 315   2016.10

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  144. 急性GVHDの治療 Reviewed International journal

    村田 誠

    臨床血液   Vol. 57 ( 10 ) page: 2176 - 2182   2016.10

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    同種造血幹細胞移植後の急性GVHDは一般にgrade II以上が治療適応となる。標準一次治療はメチルプレドニゾロン2mg/kgであるが,軽症例に限って0.5〜1.0mg/kgも経験的に投与されている。それらの有効率はドナーとの組み合わせによって異なり40〜70%程度である。一次治療開始5日後にGVHDの改善がみられない場合,もしくは3日後の時点で増悪がみられた場合には,二次治療を考慮する。ただし本邦では選択できる薬剤が少ないこともあり,一次治療開始2〜3週後に二次治療開始の判断を行うこともある。標準二次治療は確立されていない。本邦では抗胸腺細胞グロブリン製剤と間葉系幹細胞製剤が,急性GVHDに対する治療薬として保険承認を得ている。GVHD治療法に関する新しいエビデンスの発信が期待されている。(著者抄録)

  145. Programmed Death-Ligand 1 on Antigen-presenting Cells Facilitates the Induction of Antigen-specific Cytotoxic T Lymphocytes: Application to Adoptive T-Cell Immunotherapy. Reviewed International journal

    Tatsunori Goto, Tetsuya Nishida, Erina Takagi, Kotaro Miyao, Daisuke Koyama, Reona Sakemura, Ryo Hanajiri, Keisuke Watanabe, Nobuhiko Imahashi, Seitaro Terakura, Makoto Murata, Hitoshi Kiyoi

    Journal of immunotherapy (Hagerstown, Md. : 1997)   Vol. 39 ( 8 ) page: 306 - 15   2016.10

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    Programmed death-ligand 1 (PD-L1) binds to programmed death-1 (PD-1) on activated T cells and contributes to T-cell exhaustion. PD-L1 expressed on antigen-presenting cells (APCs) could be thought to inhibit the induction of Ag-specific cytotoxic T lymphocytes (CTLs) by transducing negative signal into T cells; however, the roles of PD-L1 on APCs have not yet been well examined. Therefore, we evaluated the roles of PD-L1 on APCs in the induction of Ag-specific CTLs. CD3 T cells isolated from cytomegalovirus (CMV)-seropositive healthy donors were stimulated with mature dendritic cells pulsed with CMV pp65-derived HLA-restricted peptides in the presence of anti-PD-L1 blocking antibody. Unexpectedly, PD-L1 blockade resulted in a less efficient induction of CMV-specific CTLs, suggesting that PD-L1 play a positive role in the induction of Ag-specific CTLs. For further evaluations and application to adoptive immunotherapy, we generated K562-based artificial APCs, which were retrovirally transduced with HLA class I molecules and various combinations of CD80/86 and PD-L1. K562/HLA+CD80/86+PD-L1 cells produced significantly higher induction of CMV-specific CTLs than K562/HLA or K562/HLA+CD80/86 cells without causing excessive differentiation or functional exhaustion of the induced CTLs, whereas PD-L1 itself did not have a stimulatory effect. Furthermore, only K562/HLA+CD80/86+PD-L1 cells pulsed with HLA-A*24:02-restricted Wilms tumor 1 (WT1) peptide clearly expanded WT1-specific CTLs from healthy donors. Our findings presumed that PD-L1 expressed on APCs along with CD80/86 enhanced the induction of Ag-specific CTLs probably depending on fine-tuning excessive stimulation of CD80/86, and that K562/HLA+CD80/86+PD-L1 cells has therapeutic potential as a novel type of artificial APCs for adoptive immunotherapy.

    DOI: 10.1097/CJI.0000000000000136

    PubMed

  146. A Tet-On Inducible System for Controlling CD19-Chimeric Antigen Receptor Expression upon Drug Administration. Reviewed International journal

    Reona Sakemura, Seitaro Terakura, Keisuke Watanabe, Jakrawadee Julamanee, Erina Takagi, Kotaro Miyao, Daisuke Koyama, Tatsunori Goto, Ryo Hanajiri, Tetsuya Nishida, Makoto Murata, Hitoshi Kiyoi

    Cancer immunology research   Vol. 4 ( 8 ) page: 658 - 668   2016.8

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    T cells genetically modified with a CD19 chimeric antigen receptor (CD19CAR) are remarkably effective against B-cell malignancies in clinical trials. However, major concerns remain regarding toxicities, such as hypogammaglobulinemia, due to B-cell aplasia or severe cytokine release syndrome after overactivation of CAR T cells. To resolve these adverse events, we aimed to develop an inducible CAR system by using a tetracycline regulation system that would be activated only in the presence of doxycycline (Dox). In this study, the second-generation CD19CAR was fused into the third-generation Tet-On vector (Tet-CD19CAR) and was retrovirally transduced into primary CD8(+) T cells. Tet-CD19CAR T cells were successfully generated and had minimal background CD19CAR expression without Dox. Tet-CD19CAR T cells in the presence of Dox were equivalently cytotoxic against CD19(+) cell lines and had equivalent cytokine production and proliferation upon CD19 stimulation, compared with conventional CD19CAR T cells. The Dox(+) Tet-CD19CAR T cells also had significant antitumor activity in a xenograft model. However, without Dox, Tet-CD19CAR T cells lost CAR expression and CAR T-cell functions in vitro and in vivo, clearly segregating the "On" and "Off" status of Tet-CD19CAR cells by Dox administration. In addition to suicide-gene technology, controlling the expression and the functions of CAR with an inducible vector is a potential solution for CAR T-cell therapy-related toxicities, and may improve the safety profile of CAR T-cell therapy. This strategy might also open the way to treat other malignancies in combination with other CAR or TCR gene-modified T cells. Cancer Immunol Res; 4(8); 658-68. ©2016 AACRSee related Spotlight by June, p. 643.

    DOI: 10.1158/2326-6066.CIR-16-0043

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    PubMed

  147. Graft-versus-Host Disease after HLA-Matched Sibling Bone Marrow or Peripheral Blood Stem Cell Transplantation: Comparison of North American Caucasian and Japanese Populations. Reviewed International journal

    Junya Kanda, Ruta Brazauskas, Zhen-Huan Hu, Yachiyo Kuwatsuka, Koji Nagafuji, Heiwa Kanamori, Yoshinobu Kanda, Koichi Miyamura, Makoto Murata, Takahiro Fukuda, Hisashi Sakamaki, Fumihiko Kimura, Sachiko Seo, Mahmoud Aljurf, Ayami Yoshimi, Giuseppe Milone, William A Wood, Celalettin Ustun, Shahrukh Hashimi, Marcelo Pasquini, Carmem Bonfim, Jignesh Dalal, Theresa Hahn, Yoshiko Atsuta, Wael Saber

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   Vol. 22 ( 4 ) page: 744 - 751   2016.4

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    The risk of acute graft-versus-host disease (GVHD) after HLA-matched sibling bone marrow transplantation (BMT) is lower in Japanese than in Caucasian patients. However, race may have differential effect on GVHD dependent on the graft source. North American Caucasian and Japanese patients receiving their first allogeneic BMT or peripheral blood stem cell transplantation from an HLA-matched sibling for leukemia were eligible. BMT was performed in 13% of the Caucasian patients and in 53% of the Japanese patients. On multivariate analysis, the interaction term between race and graft source was not significant in any of the models, indicating that graft source does not affect the impact of race on outcomes. The risk of grade III or IV acute GVHD was significantly lower in the Japanese patients compared with the Caucasian patients (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57 to 0.96), which resulted in lower risk of nonrelapse mortality in the Japanese patients (HR, 0.69; 95% CI, 0.54 to 0.89). The risk of relapse was also lower in this group. The lower risks of nonrelapse mortality and relapse resulted in lower overall mortality rates among the Japanese patients. In conclusion, our data indicate that irrespective of graft source, the risk of severe acute GVHD is lower in Japanese patients, resulting in a lower risk of nonrelapse mortality.

    DOI: 10.1016/j.bbmt.2015.12.027

    PubMed

  148. 間葉系幹細胞の造血幹細胞移植への応用 Reviewed International journal

    村田 誠

    日本造血細胞移植学会雑誌   Vol. 5 ( 2 ) page: 27 - 34   2016.4

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    間葉系幹細胞(MSC)は骨髄中で微小環境を形成し造血を支持している。また免疫を負に制御する働きを持ち、自身は共刺激分子を発現していないためアロT細胞からの攻撃を免れるといった特徴を有する。同種造血幹細胞移植後の移植片対宿主病(GVHD)に対して、移植ドナーではないHLA不適合者の骨髄や臍帯血からMSCを作成し投与する試みが行われている。これまでの報告によれば、重篤な副作用はなく、ステロイド治療抵抗性急性GVHDの完全寛解率は3〜5割程度、完全寛解+部分寛解率は7割程度期待できる。一方、その造血支持作用に着目して、臍帯血移植やHLAハプロタイプ一致ドナー移植においてMSCを併用する試みも行われている。評価はまだ十分定まっていないが、一部で有効性を示す結果も報告されている。いずれもよくデザインされた比較試験で副作用や有効性について検証する必要がある。(著者抄録)

  149. A comparison of tacrolimus and cyclosporine combined with methotrexate for graft-versus-host disease prophylaxis, stratified by stem cell source: a retrospective nationwide survey. Reviewed

    Rika Sakai, Masataka Taguri, Kumi Oshima, Takehiko Mori, Hiroatsu Ago, Souichi Adachi, Satoshi Morita, Shuichi Taniguchi, Takahiro Fukuda, Kazuteru Ohashi, Tetsuya Eto, Koichi Miyamura, Koji Iwato, Naoki Kobayashi, Heiwa Kanamori, Yasuo Morishima, Tokiko Nagamura-Inoue, Hisashi Sakamaki, Yoshiko Atsuta, Makoto Murata

    International journal of hematology   Vol. 103 ( 3 ) page: 322 - 33   2016.3

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    This nationwide, retrospective study compared the efficacy of cyclosporine and tacrolimus with methotrexate (CsA/MTX and TAC/MTX) for acute graft-versus-host disease (aGVHD) prevention and transplant-related outcomes. Data were obtained from the Transplant Registry Unified Management Program of the Japan Society for Hematopoietic Cell Transplantation for ≥ 16-year-old leukemia patients who received CsA/MTX or TAC/MTX after bone marrow transplantation and peripheral blood stem cell transplantation from serological HLA-matched related donors (MRD), HLA 8/8 allele-matched, or one allele-mismatched unrelated bone marrow (UBM), or 0-2 antigen-mismatched unrelated cord blood (UCB) transplantation between January 2005 and December 2009. Separate analyses were performed for each cohort. Adjusted multivariate analyses indicated that in the MRD (n = 1524) and the UBM (n = 1466) cohorts, TAC/MTX significantly reduced grade II-IV aGVHD risk (HR 0.58, P = 0.006 and HR 0.77, P = 0.015, respectively) without affecting the other transplant-related outcomes. In the UCB cohort (n = 925), TAC/MTX significantly reduced the risk of non-relapse mortality (HR 0.63, P = 0.027) and chronic GVHD (HR 0.60, P = 0.02) without significant effects on grade II-IV aGVHD (HR 0.83, P = 0.21). Our results may provide the most up-to-date data regarding GVHD prevention in Japan.

    DOI: 10.1007/s12185-016-1939-9

    PubMed

  150. Bone marrow-derived mesenchymal stem cells (JR-031) for steroid-refractory grade III or IV acute graft-versus-host disease: a phase II/III study. Reviewed

    Kazuo Muroi, Koichi Miyamura, Masaya Okada, Takuya Yamashita, Makoto Murata, Takayuki Ishikawa, Naokuni Uike, Michihiro Hidaka, Ryoji Kobayashi, Masahiro Imamura, Junji Tanaka, Kazuteru Ohashi, Shuichi Taniguchi, Takashi Ikeda, Tetsuya Eto, Masaki Mori, Mariko Yamaoka, Keiya Ozawa

    International journal of hematology   Vol. 103 ( 2 ) page: 243 - 50   2016.2

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    Following a phase I/II study using mesenchymal stem cells (MSCs; JR-031) for steroid-refractory grade II or III acute graft-versus-host disease (aGVHD), a phase II/III study using the cells focused on steroid-refractory grade III or IV aGVHD was conducted. The number of infused MSCs and the number of MSC infusions were the same as the phase I/II study. No additional immunosuppressant was given for steroid-refractory aGVHD during the course of MSC infusions. Twenty-five patients (grade III, 22 patients and grade IV, 3 patients) were enrolled in this study. At 4 weeks after the first MSC infusions, six (24 %) and nine patients (36 %) achieved a complete response (CR) and partial response (PR), respectively. Durable CR by 24 weeks, which was the primary end-point, was obtained in 12 of 25 patients (48 %). At 52 weeks, 12 patients (48 %) treated with MSCs only (six patients) and MSCs plus additional treatments (six patients) were alive in CR. The survival was significantly better in patients showing overall response (OR; CR+PR) than in those showing no OR at 4 weeks. Adverse effects commonly associated with MSC infusions were not observed. Taken together, our two clinical trials suggest JR-031 to be effective for steroid-refractory aGVHD.

    DOI: 10.1007/s12185-015-1915-9

    PubMed

  151. Influence of melphalan plus fludarabine-conditioning regimen in elderly patients aged &gt;= 5 years with hematological malignancies Reviewed

    K. Miyao, M. Sawa, Y. Kuwatsuka, Y. Ozawa, T. Kato, A. Kohno, H. Sao, T. Nishida, H. Iida, K. Naito, H. Tsurumi, H. Taji, S. Mizuta, S. Kusumoto, K. Nakase, Y. Morishita, N. Kawashima, K. Miyamura, M. Murata

    BONE MARROW TRANSPLANTATION   Vol. 51 ( 1 ) page: 157 - 160   2016.1

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    DOI: 10.1038/bmt.2015.235

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  152. Risk factors and prognosis of hepatic acute GvHD after allogeneic hematopoietic cell transplantation Reviewed

    Y. Arai, J. Kanda, H. Nakasone, T. Kondo, N. Uchida, T. Fukuda, K. Ohashi, K. Kaida, K. Iwato, T. Eto, Y. Kanda, H. Nakamae, T. Nagamura-Inoue, Y. Morishima, M. Hirokawa, Y. Atsuta, M. Murata

    BONE MARROW TRANSPLANTATION   Vol. 51 ( 1 ) page: 96 - 102   2016.1

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    Hepatic acute GvHD (aGvHD) is associated with high mortality owing to poor response to immunosuppressive therapy. The pathogenesis of hepatic aGvHD differs from that of other lesions, and specific risk factors related to pre-transplant liver conditions should be determined. We conducted a cohort study by using a Japanese transplant registry database (N=8378). Of these subjects, 1.5% had hepatitis C virus Ab (HCV-Ab) and 9.4% had liver dysfunction (elevated transaminase or bilirubin levels) before hematopoietic cell transplantation (HCT). After Ha, the cumulative incidence of hepatic aGvHD was 6.7%. On multivariate analyses, HCV-Ab positivity (hazard ratio (HR), 1.93; P=0.02) and pre-transplant liver dysfunction (HR, 1.85; P&lt;0.01), as well as advanced HCT risk, unrelated donors, HLA mismatch and cyclosporine as GvHD prophylaxis, were significant risk factors for hepatic aGvHD, whereas hepatitis B virus surface Ag was not. Hepatic aGvHD was a significant risk factor for low overall survival and high transplant-related mortality in all aGvHD grades (P &lt; 0.01). This study is the first to show the relationship between pre-transplant liver conditions and hepatic aGvHD. A prospective study is awaited to validate the results of this study and establish a new strategy especially for high-risk patients.

    DOI: 10.1038/bmt.2015.205

    Web of Science

  153. Treatment of acute graft-versus-host disease. Reviewed

    Makoto Murata

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 57 ( 10 ) page: 2176 - 2182   2016

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    Methylprednisolone administered at a dose of 2 mg/kg is a standard first-line systemic therapy for grade II to IV acute graft-versus-host disease (GVHD). Lower dose methylprednisolone or prednisone, at doses of 0.5-1.0 mg/kg, is also accepted as a first-line therapy for mild acute GVHD. Response rates of grade II to IV acute GVHD to systemic corticosteroid therapy in Japanese patients range from 40-70%, depending on the donors. No improvement within 5 days after first-line therapy or progression within 3 days after first-line therapy could make patients eligible for second-line treatment. However, due to there being few treatment options for steroid-resistant acute GVHD, decisions to initiate second-line treatment are on occasion made 2-3 weeks after first-line therapy in Japan. Previous studies do not support the choice of any specific agent for second-line treatment of acute GVHD. Anti-thymocyte globulin and mesenchymal stem cells are covered by health insurance in Japan. Establishment of new evidence for GVHD treatment is required.

    PubMed

  154. Adoptive Transfer of WT1-Specific TCR Gene-Transduced Lymphocytes in Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia Reviewed

    Tawara Isao, Masuya Masahiro, Kageyama Shinichi, Nishida Tetsuya, Terakura Seitaro, Murata Makoto, Fujiwara Hiroshi, Akatsuka Yoshiki, Ikeda Hiroaki, Miyahara Yoshihiro, Tomura Daisuke, Nukaya Ikuei, Takesako Kazutoh, Emi Nobuhiko, Yasukawa Masaki, Katayama Naoyuki, Shiku Hiroshi

    BLOOD   Vol. 126 ( 23 )   2015.12

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  155. 造血幹細胞移植 課題とこれから Reviewed

    村田 誠

    日本検査血液学会雑誌   Vol. 16 ( 3 ) page: 324 - 331   2015.11

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    我が国初の骨髄移植が行われてから約40年が経過し、その間、末梢血幹細胞や臍帯血も移植細胞源として用いられるようになった。移植1週間ほど前から大量の抗がん剤投与と大量の放射線照射による移植前処置が行われるが、その強い副作用のため、従来は移植適応が50歳前後までに制限されていた。しかし毒性を弱めた骨髄非破壊的前処置法が開発され、65歳前後まで適応が拡大された。移植片対宿主病は、生着したドナー由来免疫細胞、主としてTリンパ球が患者組織を傷害する結果発症する移植後合併症である。急性と慢性に分けられるが、いずれも標準一次治療は副腎皮質ステロイドの全身投与である。一方、ドナー由来免疫細胞は移植後患者体内に残存した白血病細胞も傷害し、その結果、抗腫瘍効果が得られる(移植片対白血病効果)。従って同種造血幹細胞移植は免疫療法だといえる。近年本邦では年間5,000件を超える造血幹細胞移植が行われており、その7割(約3,500件)が同種移植、さらにその7割(約2,500件)が骨髄バンクもしくは臍帯血バンクからの非血縁者移植である。急性白血病第一寛解期の患者では、血縁者間移植、非血縁者間移植ともに約6割の5年後生存率が得られる。2012年、「移植に用いる造血幹細胞の適切な提供の推進に関する法律」が制定された。(著者抄録)

  156. 急性GVHDの予防 Reviewed

    村田 誠

    臨床血液   Vol. 56 ( 10 ) page: 2144 - 2152   2015.10

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    同種造血幹細胞移植後の急性GVHDは重症化すると治療関連死亡の原因となるため適切な予防を行う必要がある。ヒト白血球抗原適合ドナーからの骨髄移植と末梢血幹細胞移植における標準的GVHD予防法はカルシニューリン阻害薬(シクロスポリンまたはタクロリムス)とメトトレキサートの組み合わせであり,それらの投与量や目標血中濃度に関する研究結果は多く報告されている。メトトレキサートに代えてミコフェノール酸モフェチルを使用した場合には粘膜障害が軽減する。抗胸腺細胞グロブリンの使用により重症急性GVHDとさらに全身型慢性GVHDの発症率が低下する。ただし生存率向上には寄与しない。臍帯血移植やハプロ移植におけるGVHD予防法はまだ標準化されていない。その他に免疫抑制作用を有する新しい薬剤,制御性T細胞,間葉系幹細胞の使用も試みられている。日本からのGVHD予防法に関する新しいエビデンスの発信が期待される。(著者抄録)

  157. Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection Reviewed

    R. Hanajiri, M. Murata, K. Sugimoto, M. Murase, R. Sakemura, T. Goto, K. Watanabe, N. Imahashi, S. Terakura, H. Ohashi, Y. Akatsuka, S. Kurahashi, K. Miyamura, H. Kiyoi, T. Nishida, T. Naoe

    BONE MARROW TRANSPLANTATION   Vol. 50 ( 9 ) page: 1187 - 1194   2015.9

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    In allo-stem cell transplantation (SCT), it is unclear whether donor-specific anti-HLA Abs (DSAs) can actually mediate graft rejection or if they are simply surrogate markers for the cellular immunity that causes graft rejection. Here, we first analyzed a case of cord blood allograft rejection in which DSA and cytotoxic T lymphocyte (CTL) specific for donor HLA-B*54:01 were detected at the time of graft rejection. Both the DSA and CTL inhibited colony formation by unrelated bone marrow mononuclear cells sharing HLA-B*54:01, suggesting that the humoral and cellular immune responses were involved in the graft rejection. Interestingly, the DSA and CTL were also detected in cryopreserved pre-transplant patient blood, raising a hypothesis that the presence of anti-HLA Abs could be an indicator for corresponding HLA-specific T cells. We then evaluated the existence of HLA-specific CD8(+) T cells in other patient blood specimens having anti-HLA class I Abs. Interferon-gamma enzyme-linked innmunospot assays clearly confirmed the existence of corresponding HLA-specific T-cell precursors in three of seven patients with anti-HLA Abs. In conclusion, our data demonstrate that integrated humoral and cellular immunity recognizing the same alloantigen of the donor can mediate graft rejection in DSA-positive patients undergoing HLA-mismatched allo-SCT. Further studies generalizing our observation are warranted.

    DOI: 10.1038/bmt.2015.119

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  158. Chimerism status after unrelated donor bone marrow transplantation with fludarabine-melphalan conditioning is affected by the melphalan dose and is predictive of relapse. Reviewed International journal

    Nobuhiko Imahashi, Haruhiko Ohashi, Seitaro Terakura, Kotaro Miyao, Reona Sakemura, Tomonori Kato, Masashi Sawa, Emi Yokohata, Shingo Kurahashi, Yukiyasu Ozawa, Tetsuya Nishida, Hitoshi Kiyoi, Koichi Watamoto, Akio Kohno, Masanobu Kasai, Chiaki Kato, Hiroatsu Iida, Tomoki Naoe, Koichi Miyamura, Makoto Murata

    Annals of hematology   Vol. 94 ( 7 ) page: 1139 - 48   2015.7

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    Little is known regarding the chimerism status after reduced-intensity conditioning transplantation when bone marrow is used as a stem cell source. We prospectively analyzed lineage-specific chimerism and retrospectively evaluated clinical outcomes in 80 adult patients who underwent unrelated donor bone marrow transplantation (URBMT) with fludarabine plus melphalan (FM) as the conditioning regimen. Mixed donor chimerism (MDC) was seen in 43 and 10 % of patients at days 14 and 28, respectively. Melphalan at ≤130 mg/m(2) was associated with an increased incidence of MDC at day 28 (P = 0.03). Patients with MDC at day 14 showed a marginally increased risk of primary graft failure and a marginally decreased risk of graft-versus-host disease. In multivariate analysis, MDC at day 14 was associated with higher overall mortality (hazard ratio (HR) = 2.1; 95 % confidence interval (CI), 1.1-4.2; P = 0.04) and relapse rate (HR = 3.0; 95 % CI, 1.2-7.5; P = 0.02), but not with non-relapse mortality (HR = 1.8; 95 % CI, 0.70-4.6; P = 0.23). Thus, the FM regimen yields prompt complete donor chimerism after URBMT, but the melphalan dose significantly impacts the kinetics of chimerism. Chimerism status evaluation at day 14 may be instrumental in predicting relapse after URBMT with the FM regimen.

    DOI: 10.1007/s00277-015-2312-4

    PubMed

  159. Prophylactic and therapeutic treatment of graft-versus-host disease in Japan. Reviewed

    Makoto Murata

    International Journal of Hematology   Vol. 101 ( 5 ) page: 467 - 486   2015.5

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    Allogeneic hematopoietic stem cell transplantation in Japan is very different from that in Western countries in terms of the homogeneous genetic background, the preference for bone marrow to peripheral blood stem cells, use of a single unit in cord blood transplantation, and frequent use of non-myeloablative preconditioning due to a large number of elderly patients. Therefore, conclusions obtained from well-designed prospective and/or comparative studies of treatment of graft-versus-host disease (GVHD) performed in the United States or Europe may not fit Japanese transplant patients. This article reviews the studies of prophylactic and therapeutic treatment of acute and chronic GVHD that have been conducted in Japan. A randomized study demonstrated a lower incidence of acute GVHD in tacrolimus-based prophylaxis than in cyclosporine A-based prophylaxis. Retrospective and non-randomized prospective studies suggest that cyclosporine A-based and tacrolimus-based GVHD prophylaxis regimens are well researched and nearly optimized for Japanese patients, including infusion methods and target blood concentration. However, most other studies were performed in a single institute including a small number of patients, resulting in biased conclusions. There is no conclusive report on steroid-refractory acute and chronic GVHD. This review provides a baseline for starting prospective studies to create new evidence for GVHD treatment from Japan.

    DOI: 10.1007/s12185-015-1784-2

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  160. Recent topics in graft-versus-host disease: from the perspectives of pathogenesis and treatment. Reviewed

    Makoto Murata

    International journal of hematology   Vol. 101 ( 5 ) page: 426 - 427   2015.5

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    DOI: 10.1007/s12185-015-1789-x

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  161. Impact of conditioning intensity and TBI on acute GVHD after hematopoietic cell transplantation

    H. Nakasone, T. Fukuda, J. Kanda, T. Mori, S. Yano, T. Kobayashi, K. Miyamura, T. Eto, H. Kanamori, K. Iwato, N. Uchida, S. Mori, T. Nagamura-Inoue, T. Ichinohe, Y. Atsuta, T. Teshima, M. Murata, G. w. g. o, t. J, S. o, H. C. Transplantation

    Bone Marrow Transplant   Vol. 50 ( 4 ) page: 559 - 65   2015.4

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    The impact of the conditioning intensity and TBI on acute GVHD (aGVHD) is still a matter of debate. We analyzed 6848 adult recipients who received allogeneic hematopoietic cell transplants (HCT) between 2006 and 2011 in Japan. The subjects were divided into groups who had received myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC), either with or without TBI. There was a significant difference in the incidence of aGVHD 2-4 among the different conditioning types: 39% in TBI-MAC, 35% in TBI-RIC and 32% in both no-TBI MAC and no-TBI-RIC (P&lt;0.001). In a multivariate analysis, TBI-MAC, but not no-TBI MAC, was significantly associated with an increased risk of aGVHD 2-4 (hazard ratio (HR) 1.33, P&lt;0.01), whereas TBI-RIC was associated with an increased risk of GVHD 3-4 (HR 1.36, P=0.048). TBI-MAC and TBI-RIC were significantly associated with skin and gastrointestinal aGVHD. Subgroup analyses demonstrated that not only TBI-MAC, but also TBI-RIC, was significantly associated with aGVHD 2-4 in older patients. Furthermore, high-dose TBI only had an adverse impact on aGVHD 2-4 in HLA-matched HCT. Impacts of intensity and TBI on aGVHD differ by patient backgrounds, and th

    DOI: 10.1038/bmt.2014.293

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  162. Biological significance of HLA locus matching in unrelated donor bone marrow transplantation. Reviewed International journal

    Yasuo Morishima, Koichi Kashiwase, Keitaro Matsuo, Fumihiro Azuma, Satoko Morishima, Makoto Onizuka, Toshio Yabe, Makoto Murata, Noriko Doki, Tetsuya Eto, Takehiko Mori, Koichi Miyamura, Hiroshi Sao, Tatsuo Ichinohe, Hiroo Saji, Shunichi Kato, Yoshiko Atsuta, Keisei Kawa, Yoshihisa Kodera, Takehiko Sasazuki

    Blood   Vol. 125 ( 7 ) page: 1189 - 97   2015.2

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    We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell-replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLA-DQB1 double (DRB1_DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1_DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1_DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection.

    DOI: 10.1182/blood-2014-10-604785

    PubMed

  163. Target antigen density governs the efficacy of anti-CD20-CD28-CD3 ζ chimeric antigen receptor-modified effector CD8+ T cells. Reviewed International journal

    Keisuke Watanabe, Seitaro Terakura, Anton C Martens, Tom van Meerten, Susumu Uchiyama, Misa Imai, Reona Sakemura, Tatsunori Goto, Ryo Hanajiri, Nobuhiko Imahashi, Kazuyuki Shimada, Akihiro Tomita, Hitoshi Kiyoi, Tetsuya Nishida, Tomoki Naoe, Makoto Murata

    Journal of immunology (Baltimore, Md. : 1950)   Vol. 194 ( 3 ) page: 911 - 20   2015.2

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    The effectiveness of chimeric Ag receptor (CAR)-transduced T (CAR-T) cells has been attributed to supraphysiological signaling through CARs. Second- and later-generation CARs simultaneously transmit costimulatory signals with CD3ζ signals upon ligation, but may lead to severe adverse effects owing to the recognition of minimal Ag expression outside the target tumor. Currently, the threshold target Ag density for CAR-T cell lysis and further activation, including cytokine production, has not yet been investigated in detail. Therefore, we determined the threshold target Ag density required to induce CAR-T cell responses using novel anti-CD20 CAR-T cells with a CD28 intracellular domain and a CD20-transduced CEM cell model. The newly developed CD20CAR-T cells demonstrated Ag-specific lysis and cytokine secretion, which was a reasonable level as a second-generation CAR. For lytic activity, the threshold Ag density was determined to be ∼200 molecules per target cell, whereas the Ag density required for cytokine production of CAR-T cells was ∼10-fold higher, at a few thousand per target cell. CD20CAR-T cells responded efficiently to CD20-downregulated lymphoma and leukemia targets, including rituximab- or ofatumumab-refractory primary chronic lymphocytic leukemia cells. Despite the potential influence of the structure, localization, and binding affinity of the CAR/Ag, the threshold determined may be used for target Ag selection. An Ag density below the threshold may not result in adverse effects, whereas that above the threshold may be sufficient for practical effectiveness. CD20CAR-T cells also demonstrated significant lytic activity against CD20-downregulated tumor cells and may exhibit effectiveness for CD20-positive lymphoid malignancies.

    DOI: 10.4049/jimmunol.1402346

    PubMed

  164. Simple and Efficient Generation of Virus-specific T Cells for Adoptive Therapy Using Anti-4-1BB Antibody Reviewed International journal

    Nobuhiko Imahashi, Tetsuya Nishida, Tatsunori Goto, Seitaro Terakura, Keisuke Watanabe, Ryo Hanajiri, Reona Sakemura, Misa Imai, Hitoshi Kiyoi, Tomoki Naoe, Makoto Murata

    JOURNAL OF IMMUNOTHERAPY   Vol. 38 ( 2 ) page: 62 - 70   2015.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Although recent studies of virus-specific T-cell (VST) therapy for viral infections after allogeneic hematopoietic stem cell transplantation have shown promising results, simple and less time-intensive and labor-intensive methods are required to generate VSTs for the wider application of VST therapy. We investigated the efficacy of anti-CD28 and anti-4-1BB antibodies, which can provide T cells with costimulatory signals similar in strength to those of antigen-presenting cells, in generating VSTs. When peripheral blood mononuclear cells were stimulated with viral peptides together with isotype control, anti-CD28, or anti-4-1BB antibodies, anti-4-1BB antibodies yielded the highest numbers of VSTs, which were on an average 7.9 times higher than those generated with isotype control antibody. The combination of anti-CD28 and anti-4-1BB antibodies did not result in increased numbers of VSTs compared with anti-4-1BB antibody alone. Importantly, the positive effect of anti-4-1BB antibody was observed regardless of the epitopes of the VSTs. In contrast, the capacity of dendritic cells (DCs) to generate VSTs differed considerably depending on the epitopes of the VSTs. Furthermore, the numbers of VSTs generated with DCs were at most similar to those generated with the anti-4-1BB antibody. Generation of VSTs with anti-4-1BB antibody did not result in excessive differentiation or deteriorated function of the generated VSTs compared with those generated with control antibody or DCs. In conclusion, VSTs can be generated rapidly and efficiently by simply stimulating peripheral blood mononuclear cells with viral peptide and anti-4-1BB antibody without using antigen-presenting cells. We propose using anti-4-1BB antibody as a novel strategy to generate VSTs for adoptive therapy.

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  165. Age influences post-graft-versus-host disease non-relapse mortality in adults with acute graft-versus-host disease of varying severity following allogeneic hematopoietic cell transplant. Reviewed International journal

    Takahiko Nakane, Takahiro Fukuda, Junya Kanda, Shuichi Taniguchi, Tetsuya Eto, Kazuteru Ohashi, Hirohisa Nakamae, Mineo Kurokawa, Takehiko Mori, Yasuo Morishima, Tokiko Nagamura-Inoue, Hisashi Sakamaki, Yoshiko Atsuta, Makoto Murata

    Leukemia & lymphoma   Vol. 56 ( 8 ) page: 2392 - 7   2015

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    We retrospectively analyzed 2682 patients who developed grade II-IV acute graft-versus-host disease (GVHD). On analysis with stratification into five age groups (20-29, 30-39, 40-49, 50-59 and ≥60), 2-year non-relapse mortality rates (NRM) after the onset of GVHD were 20.7, 26.2, 26.6, 37.0 and 40.4%, respectively (p<0.001). We found a significant interaction between the patient's age and GVHD severity with respect to NRM (p=0.004). On multivariate analyses stratified by GVHD severity, the hazard ratio (HR) for NRM in the groups aged 50 years or more (reference: age group 20-29) was about twice as great in patients with grade II acute GVHD when compared with grade III-IV disease (HR in those aged 50-59 years: 2.9 for grade II and 1.5 [p=0.03 and 0.04] for grades III-IV; HR if ≥60 years: 3.3 for grade II and 1.5 for grades III-IV [p<0.001 for both]).

    DOI: 10.3109/10428194.2015.1009056

    PubMed

  166. Simple and Efficient Generation of Virus-specific T Cells for Adoptive Therapy Using Anti-4-1BB Antibody Reviewed

    Imahashi Nobuhiko, Nishida Tetsuya, Goto Tatsunori, Terakura Seitaro, Watanabe Keisuke, Hanajiri Ryo, Sakemura Reona, Imai Misa, Kiyoi Hitoshi, Naoe Tomoki, Murata Makoto

    JOURNAL OF IMMUNOTHERAPY   Vol. 38 ( 2 ) page: 62 - 70   2015

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  167. Treatment of patients with adult T cell leukemia/lymphoma with cord blood transplantation: a Japanese nationwide retrospective survey. Reviewed International journal

    Koji Kato, Ilseung Choi, Atsushi Wake, Naokuni Uike, Shuichi Taniguchi, Yukiyoshi Moriuchi, Yasushi Miyazaki, Hirohisa Nakamae, Eijirou Oku, Makoto Murata, Tetsuya Eto, Koichi Akashi, Hisashi Sakamaki, Koji Kato, Ritsuro Suzuki, Takeharu Yamanaka, Atae Utsunomiya

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   Vol. 20 ( 12 ) page: 1968 - 74   2014.12

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    Allogeneic bone marrow and peripheral blood stem cell transplantations are curative treatment modalities for adult T cell leukemia/lymphoma (ATLL) because of the intrinsic graft-versus-ATLL effect. However, limited information is available regarding whether cord blood transplantation (CBT) induces a curative graft-versus-ATLL effect against aggressive ATLL. To evaluate the effect of CBT against ATLL, we retrospectively analyzed data from 175 patients with ATLL who initially underwent single-unit CBT. The 2-year overall survival (OS) rate was 20.6% (95% confidence interval [CI], 13.8% to 27.4%). A multivariate analysis revealed that the development of graft-versus-host disease (GVHD) was a favorable prognostic factor for OS (hazard ratio, .10; 95% CI, .01 to .94; P = .044). Furthermore, the 2-year OS (42.7%; 95% CI, 28.1% to 56.6%) of patients with grade 1 to 2 acute GVHD was higher than that of patients without acute GVHD (24.2%; 95% CI, 11.2% to 39.8%; P = .048). However, the cumulative incidence of treatment-related mortality (TRM) was high (46.1%; 95% CI, 38.2% to 53.7%), and early death was particularly problematic. In conclusion, CBT cures patients with ATLL partly through a graft-versus-ATLL effect. However, novel interventions will be required, particularly in the early phase, to reduce TRM and optimize GVHD.

    DOI: 10.1016/j.bbmt.2014.08.012

    PubMed

  168. Mycophenolate mofetil use after unrelated hematopoietic stem cell transplantation for prophylaxis and treatment of graft-vs.-host disease in adult patients in Japan. Reviewed International journal

    Minako Iida, Takahiro Fukuda, Naoyuki Uchida, Makoto Murata, Nobuyuki Aotsuka, Kentaro Minagawa, Kazuteru Oohashi, Kentaro Fukushima, Tadakazu Kondo, Tetsuya Eto, Toshihiro Miyamoto, Yasuo Morishima, Tokiko Nagamura, Yoshiko Atsuta, Ritsuro Suzuki

    Clinical transplantation   Vol. 28 ( 9 ) page: 980 - 9   2014.9

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    Our previous study of 301 patients who received hematopoietic stem cell transplantation (HSCT) from related donors demonstrated the efficacy of mycophenolate mofetil (MMF) for prophylaxis and treatment of graft-vs.-host disease (GVHD). In this study, we investigated the safety and efficacy of MMF in 716 adult patients who received unrelated HSCT. The incidences of Grade II-IV and III-IV acute GVHD in the prophylactic administration group were 38.3% and 14.3%, respectively. These rates were not statistically significant when evaluating the MMF dosage and graft source. The incidences of limited and extensive chronic GVHD were 16.6% and 11.1%, respectively. In the therapeutic administration group, 69.1% of the subjective symptoms for both acute and chronic GVHD improved. With respect to the adverse events, 75 infections and 50 cases of diarrhea were observed, and the frequency of these events increased with increasing MMF dose. The overall survival rate was 36.4% after a median follow-up period of three yr. This study shows that MMF is safe and effective for the prevention and treatment of GVHD in patients who have received HSCT from unrelated donors.

    DOI: 10.1111/ctr.12405

    PubMed

  169. Successful unrelated cord blood transplantation for adult acquired aplastic anemia using reduced intensity conditioning without ATG. Reviewed International journal

    Seitaro Terakura, Tetsuya Nishida, Yoshihiro Inamoto, Haruhiko Ohashi, Tomoki Naoe, Makoto Murata

    Immunology letters   Vol. 160 ( 1 ) page: 99 - 101   2014.7

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    DOI: 10.1016/j.imlet.2014.01.013

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  170. Dexamethasone Palmitate Ameliorates Macrophages-Rich Graft-versus-Host Disease by Inhibiting Macrophage Functions Reviewed International journal

    Satoshi Nishiwaki, Takayuki Nakayama, Makoto Murata, Tetsuya Nishida, Seitaro Terakura, Shigeki Saito, Tomonori Kato, Hiroki Mizuno, Nobuhiko Imahashi, Aika Seto, Yukiyasu Ozawa, Koichi Miyamura, Masafumi Ito, Kyosuke Takeshita, Hidefumi Kato, Shinya Toyokuni, Keisuke Nagao, Ryuzo Ueda, Tomoki Naoe

    PLOS ONE   Vol. 9 ( 5 )   2014.5

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    Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-alpha and IFN-gamma, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.

    DOI: 10.1371/journal.pone.0096252

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  171. Allogeneic transplantation for primary myelofibrosis with BM, peripheral blood or umbilical cord blood: an analysis of the JSHCT Reviewed International journal

    M. Murata, T. Nishida, S. Taniguchi, K. Ohashi, H. Ogawa, T. Fukuda, T. Mori, H. Kobayashi, C. Nakaseko, N. Yamagata, Y. Morishima, T. Nagamura-Inoue, H. Sakamaki, Y. Atsuta, R. Suzuki, T. Naoe

    BONE MARROW TRANSPLANTATION   Vol. 49 ( 3 ) page: 355 - 360   2014.3

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    To determine whether a difference in donor source affects the outcome of transplantation for patients with primary myelofibrosis (PMF), a retrospective study was conducted using the national registry data on patients who received first allogeneic hematopoietic cell transplantation (HCT) with related BM (n= 19), related PBSCs (n=25), unrelated BM (n=28) or unrelated umbilical cord blood (UCB; n= 11). The 5-year OS rates after related BM, related PBSC and unrelated BM transplantation were 63%, 43% and 41%, respectively, and the 2-year OS rate after UCB transplantation was 36%. On multivariate analysis, the donor source was not a significant factor for predicting the OS rate. Instead, performance status (PS) &gt;= 2 (vs PS 0-1) predicted a lower OS (P= 0.044), and RBC transfusion &gt;= 20 times before transplantation (vs transfusion &lt;= 9 times) showed a trend toward a lower OS (P= 0.053). No advantage of nonmyeloablative preconditioning regimens in terms of decreasing nonrelapse mortality or increasing OS was found. Allogeneic HCT, and even unrelated BM and UCB transplantation, provides a curative treatment for PMF patients.

    DOI: 10.1038/bmt.2013.180

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  172. Leukemic evolution of donor-derived cells harboring IDH2 and DNMT3A mutations after allogeneic stem cell transplantation Reviewed International journal

    T. Yasuda, T. Ueno, K. Fukumura, A. Yamato, M. Ando, H. Yamaguchi, M. Soda, M. Kawazu, E. Sai, Y. Yamashita, M. Murata, H. Kiyoi, T. Naoe, H. Mano

    LEUKEMIA   Vol. 28 ( 2 ) page: 426 - 428   2014.2

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    DOI: 10.1038/leu.2013.278

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  173. Risk factors and organ involvement of chronic GVHD in Japan Reviewed International journal

    J. Kanda, H. Nakasone, Y. Atsuta, T. Toubai, H. Yokoyama, T. Fukuda, S. Taniguchi, K. Ohashi, H. Ogawa, T. Eto, K. Miyamura, Y. Morishima, T. Nagamura-Inoue, H. Sakamaki, M. Murata

    BONE MARROW TRANSPLANTATION   Vol. 49 ( 2 ) page: 228 - 235   2014.2

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    Few studies have evaluated the risk factors for chronic GVHD and organ involvement associated with different graft types, including unrelated cord blood (U-CB). We retrospectively studied 4818 adult patients who received their first allogeneic transplantation and survived for at least 100 days. The incidence of chronic GVHD at 2 years was 37%. The following factors were associated with the development of chronic GVHD: female donor/male recipient, CMV-Ab seropositivity, matched related peripheral blood grafts vs matched related BM grafts, no in vivo T-cell depletion and the occurrence of grade II-IV acute GVHD. Among these factors, the association with acute GVHD occurrence was consistently significant across donor subtypes. The use of U-CB was not associated with chronic GVHD, but was associated with a low incidence of extensive chronic GVHD. Chronic GVHD patients who had received U-CB transplants showed less frequent involvement of the oral cavity (28% vs 55%), eye (12% vs 26%), liver (20% vs 44%), lung (11% vs 25%) and joint (0% vs 6%) than those with matched related BM grafts. In conclusion, we found that U-CB transplants were associated with a low incidence of extensive chronic GVHD and less frequent involvement of the oral cavity, eye, liver, lung and joints.

    DOI: 10.1038/bmt.2013.151

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  174. Correlations of programmed death 1 expression and serum IL-6 level with exhaustion of cytomegalovirus-specific T cells after allogeneic hematopoietic stem cell transplantation Reviewed International journal

    Tomonori Kato, Tetsuya Nishida, Yoshinori Ito, Miho Murase, Makoto Murata, Tomoki Naoe

    CELLULAR IMMUNOLOGY   Vol. 288 ( 1-2 ) page: 53 - 59   2014

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    The effect of programmed death 1 (PD-1) on cytomegalovirus (CMV)-specific T cells has not been thoroughly examined. We evaluated the involvement of exhausted CMV-specific T cells in persistent CMV infection after allogeneic hematopoietic stem cell transplantation (HSCT). CMV-specific CM T cells obtained from an HLA-A*24:02-positive patient, who failed to eliminate CMV for more than I year after HSCT, responded poorly to CMV pp65 peptide and showed high PD-1 expression. Sera from patients with persistent CMV infection showed a significantly higher IL-6 level than those from patients with temporary CMV infection after allogeneic HSCT and healthy donors. CD33(+) adherent cells produced IL-6, and regulated PD-1 expression and growth of CMV-specific CD8(+)T cells through cell-to-cell contact. Although further investigation is required to clarify the association between IL-6 level and CMV infection in more patients, IL-6 might be a useful biomarker of persistent CMV infection after allogeneic HSCT. (C) 2014 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.cellimm.2014.02.007

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  175. Identification of a novel HLA-A*24:02-restricted adenovirus serotype 11-specific CD8+ T-cell epitope for adoptive immunotherapy. Reviewed International journal

    Nobuhiko Imahashi, Tetsuya Nishida, Yoshinori Ito, Jun-ichi Kawada, Yozo Nakazawa, Shingo Toji, Susumu Suzuki, Seitaro Terakura, Tomonori Kato, Makoto Murata, Tomoki Naoe

    Molecular immunology   Vol. 56 ( 4 ) page: 399 - 405   2013.12

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    Subgroup B adenovirus serotype 11 (Ad11) occasionally causes fatal infections in immunocompromised patients. The present study describes a novel Ad11 epitope presented by HLA-A*24:02 that could be used for adoptive immunotherapy. Ten synthetic Ad11 hexon protein-derived nonamer peptides that bound to HLA-A*24:02 were selected by a computer algorithm and MHC stabilization assay. Stimulation of peripheral blood mononuclear cells from HLA-A*24:02+ donors with each of these synthetic peptides induced peptide-specific CD8(+) T-cells for three peptides. Testing the reactivity of these peptide-specific CD8(+) T-cells against various target cells confirmed that peptide TYFNLGNKF is naturally processed in Ad11-infected cells and is presented by HLA-A*24:02. Emergence of TYFNLGNKF-specific CD8(+) T-cells coincided with the clearance of adenoviruses in a patient with Ad11 disease. Importantly, TYFNLGNKF-specific CD8(+) T-cells were suggested to be not serotype cross-reactive. The novel HLA-A*24:02-restricted Ad11 epitope could be used for anti-Ad11 adoptive immunotherapy and to monitor immunity to Ad11 using MHC tetramers.

    DOI: 10.1016/j.molimm.2013.05.232

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    PubMed

  176. Identification of a novel HLA-A*24:02-restricted adenovirus serotype 11-specific CD8(+) T-cell epitope for adoptive immunotherapy. Reviewed International journal

    Imahashi N, Nishida T, Ito Y, Kawada J, Nakazawa Y, Toji S, Suzuki S, Terakura S, Kato T, Murata M, Naoe T

    Mol Immunol   Vol. 2013 ( 56 ) page: 399-405.   2013.12

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  177. Clinical factors predicting the response of acute graft-versus-host disease to corticosteroid therapy: an analysis from the GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation. Reviewed International journal

    Makoto Murata, Hideki Nakasone, Junya Kanda, Takahiko Nakane, Tatsuo Furukawa, Takahiro Fukuda, Takehiko Mori, Shuichi Taniguchi, Tetsuya Eto, Kazuteru Ohashi, Masayuki Hino, Masami Inoue, Hiroyasu Ogawa, Yoshiko Atsuta, Tokiko Nagamura-Inoue, Hiromasa Yabe, Yasuo Morishima, Hisashi Sakamaki, Ritsuro Suzuki

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   Vol. 19 ( 8 ) page: 1183 - 9   2013.8

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    Systemic corticosteroid therapy is recommended as a first-line treatment for acute graft-versus-host disease (GVHD). We performed a retrospective study to identify the factors affecting the response of grade II to IV acute GVHD to systemic corticosteroid therapy using the Japanese national registry data for patients who received first allogeneic hematopoietic cell transplantation with bone marrow (BM) (n = 1955), peripheral blood stem cells (PBSCs) (n = 642), or umbilical cord blood (UCB) (n = 839). Of 3436 patients, 2190 (63.7%) showed improvement of acute GVHD to first-line therapy with corticosteroids. Various factors were identified to predict corticosteroid response. Interestingly, UCB (versus HLA-matched related BM) transplantation was significantly associated with a higher probability of improvement, whereas HLA-matched unrelated BM and HLA-mismatched stem cell sources other than UCB were significantly associated with a lower probability of improvement. HLA-matched related PBSC transplantation was not significantly different from HLA-matched related BM transplantation. Patients without improvement from corticosteroid therapy had a 2.5-times higher nonrelapse mortality and a .6-times lower overall survival rate. The present study demonstrated, for the first time, a higher probability of improvement in grade II to IV acute GVHD with systemic corticosteroid therapy in patients after UCB transplantation than in those after BM and PBSC transplantation. A prospective study is warranted.

    DOI: 10.1016/j.bbmt.2013.05.003

    PubMed

  178. Unrelated allogeneic bone marrow-derived mesenchymal stem cells for steroid-refractory acute graft-versus-host disease: a phase I/II study. Reviewed

    Kazuo Muroi, Koichi Miyamura, Kazuteru Ohashi, Makoto Murata, Tetsuya Eto, Naoki Kobayashi, Shuichi Taniguchi, Masahiro Imamura, Kiyoshi Ando, Shunichi Kato, Takehiko Mori, Takanori Teshima, Masaki Mori, Keiya Ozawa

    International journal of hematology   Vol. 98 ( 2 ) page: 206 - 13   2013.8

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    We conducted a multicenter phase I/II study using mesenchymal stem cells (MSCs) manufactured from the bone marrow of healthy unrelated volunteers to treat steroid-refractory acute graft-versus-host disease (aGVHD). Fourteen patients with hematological malignancies who suffered from grade II (9 patients) or III aGVHD (5) were treated. Affected organs were gut (10 patients), skin (9 patients), and liver (3 patients). Seven patients had two involved organs. The median age was 52. No other second-line agents were given. MSCs were given at a dose of 2 × 10(6) cells/kg for each infusion twice a week for 4 weeks. If needed, patients were continuously given MSCs weekly for an additional 4 weeks. By week 4, 13 of 14 patients (92.9 %) had responded to MSC therapy with a complete response (CR; n = 8) or partial response (PR; n = 5). At 24 weeks, 11 patients (10 with CR and 1 with PR) were alive. At 96 weeks, 8 patients were alive in CR. A total of 6 patients died, attributable to the following: underlying disease relapse (2 patients), breast cancer relapse (1), veno-occlusive disease (1), ischemic cholangiopathy (1), and pneumonia (1). No clear adverse effects associated with MSC infusion were observed. Third party-derived bone marrow MSCs may be safe and effective for patients with steroid-refractory aGVHD.

    DOI: 10.1007/s12185-013-1399-4

    PubMed

  179. Efficacy and long-term outcome of treatment for pure red cell aplasia after allogeneic stem cell transplantation from major ABO-incompatible donors. Reviewed International journal

    Makoto Hirokawa, Takahiro Fukuda, Kazuteru Ohashi, Michihiro Hidaka, Tatsuo Ichinohe, Koji Iwato, Heiwa Kanamori, Makoto Murata, Toru Sakura, Masahiro Imamura, Soichi Adachi, Ritsuro Suzuki, Yasuo Morishima, Hisashi Sakamaki

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   Vol. 19 ( 7 ) page: 1026 - 32   2013.7

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    No standard of care for pure red cell aplasia (PRCA) after major ABO-incompatible hematopoietic stem cell transplantation (HSCT) has been established. We conducted a retrospective cohort study to learn the efficacy and outcome of treatment for PRCA. One hundred forty-five recipients who showed delayed recovery of erythropoiesis and survived >100 days after transplantation without early disease progression were selected from 2846 records of major ABO-incompatible transplantation in the registry database in Japan, and detailed data of 46 recipients were collected. Treatment of PRCA, such as rapid tapering of calcineurin inhibitors, corticosteroids, or additional immunosuppressants, was given to 22 patients but not to the other 24 patients. The overall response rate of the treatment group was 54.5%. The number of days from diagnosis of PRCA to recovery of reticulocytes >1% and the cumulative number of red blood cell transfusions were not significantly different between the 2 groups. Infections accounted for the death of 7 of 11 patients in the treatment group. Univariate analysis identified 5 variables influencing survival, including graft-versus-host disease, disease progression, and treatment of PRCA; disease progression remained as the only factor negatively affecting survival by multivariate analysis. The present study could not provide supportive evidence for the beneficial effects of treatment for PRCA after major ABO-mismatched HSCT.

    DOI: 10.1016/j.bbmt.2013.04.004

    PubMed

  180. A case-control study of bronchiolitis obliterans syndrome following allogeneic hematopoietic stem cell transplantation. Reviewed International journal

    Hideki Nakasone, Junya Kanda, Shingo Yano, Yoshiko Atsuta, Hiroatsu Ago, Takahiro Fukuda, Kazuhiko Kakihana, Tatsuya Adachi, Toshiaki Yujiri, Shuichi Taniguchi, Jun Taguchi, Yasuo Morishima, Tokiko Nagamura, Hisashi Sakamaki, Takehiko Mori, Makoto Murata

    Transplant international : official journal of the European Society for Organ Transplantation   Vol. 26 ( 6 ) page: 631 - 9   2013.6

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    Bronchiolitis obliterans syndrome (BOS) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, the pathogenesis and risks for the development of BOS have remained unclear. Therefore, a case-control study was conducted to investigate the risk factors for the development of BOS, which included the largest number of BOS cases; 196 patients with BOS were identified and compared with 1960 control recipients. The following were identified as significantly higher risk factors for the development of BOS: female recipients (OR 1.47, P = 0.019), ABO-mismatch HSCT (minor mismatch, OR 1.67, P = 0.015; major mismatch, OR 1.73, P = 0.012; bidirectional mismatch, OR 1.96, P = 0.018), busulfan+cyclophosphamide-based myeloablative conditioning (OR 1.74, P = 0.016), and acute graft-versus-host disease (GVHD) involving the skin (OR 1.55, P = 0.011). On the other hand, the risk for the development of BOS was significantly lower in patients receiving cord blood transplantation (OR 0.26, P = 0.0011). With respect to other target organs of chronic GVHD, ocular involvement was significantly associated with BOS (OR 2.53, P < 0.001). Prospective studies are required to elucidate the risk factors for the development of BOS, and future investigations should focus on finding a prophylactic approach against BOS based on these findings.

    DOI: 10.1111/tri.12093

    PubMed

  181. Impact of hepatitis C virus infection on clinical outcome in recipients after allogeneic hematopoietic cell transplantation. Reviewed International journal

    Hideki Nakasone, Saiko Kurosawa, Kimikazu Yakushijin, Shuichi Taniguchi, Makoto Murata, Kazuhiro Ikegame, Takeshi Kobayashi, Tetsuya Eto, Koichi Miyamura, Hisashi Sakamaki, Yasuo Morishima, Tokiko Nagamura, Ritsuro Suzuki, Takahiro Fukuda

    American journal of hematology   Vol. 88 ( 6 ) page: 477 - 84   2013.6

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    The impact of hepatitis C virus (HCV) infection on outcomes following allogeneic hematopoietic cell transplantation (HCT) remains a matter of debate. We have retrospectively examined the significance of HCV infection among recipients who received allogeneic HCT, using a Japan transplant outcome registry database between 2006 and 2009. Among 7,831 recipients, 136 were HCV-positive. The rate of hematopoietic recovery was lower in the HCV-positive group (neutrophil recovery of 500 × 10(6) /L or higher: 79% vs. 87% at Day 30, P = 0.087; platelet recovery of 50 × 10(9) /L or higher: 57% vs. 65% at Day 60, P = 0.012). The HCV-positive group had a significantly higher incidence of nonrelapse mortality 38% vs. 25% at 2 years, P < 0.01) and inferior overall survival (41% vs. 51% at 2 years, P < 0.01). A multivariate analysis revealed that HCV seropositivity was associated with an independent risk for higher nonrelapse mortality (hazard ratio: 1.65, P < 0.01) and inferior overall survival (hazard ratio: 1.39, P < 0.01). The incidences of death due to hepatic problems (8% vs. 2%, P < 0.01), bacterial infection (10% vs. 4%, P < 0.01), or graft failure (5% vs. 2%, P = 0.084) tended to be higher in the HCV-positive group. HCV infection had an adverse impact on the clinical outcome following HCT, especially in the setting of unrelated transplantation. Careful evaluation before embarking on HCT and intensive assessment against complications are warranted in HCV-infected recipients.

    DOI: 10.1002/ajh.23436

    PubMed

  182. 【臓器移植の現状と将来展望】造血幹細胞移植 Reviewed International journal

    村田 誠, 直江 知樹

    日本内科学会雑誌   Vol. 102 ( 3 ) page: 585 - 591   2013.3

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  183. 造血幹細胞移植の話題 ASH発表演題より Reviewed International journal

    豊嶋 崇徳, 高見 昭良, 谷口 修一, 村田 誠

    Therapeutic Research   Vol. 34 ( 3 ) page: 259 - 266   2013.3

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  184. 【間葉系幹細胞を用いた細胞治療】間葉系幹細胞による急性GVHDの治療 Reviewed International journal

    村田 誠

    血液フロンティア   Vol. 23 ( 4 ) page: 473 - 478   2013.3

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    同種造血幹細胞移植後の急性移植片対宿主病(GVHD)に対する治療法として、間葉系幹細胞(MSC)の輸注が試みられている。文献レベルで数百症例の投与報告があり、HLA不一致の第三者(患者でも移植ドナーでもない)のMSCも用いられているが、これまでのところ重篤な副作用は報告されていない。治療効果は、対象としたGVHDの重症度やMSC輸注時の併用薬剤が異なることから報告によるばらつきが大きいが、ステロイド一次治療無効急性GVHDの寛解率は3割程度、寛解+部分寛解率は7割程度とする報告が多い。良くデザインされた比較試験での検証が望まれる。(著者抄録)

  185. Efficacy and safety of human adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis. Reviewed

    Satoshi Nishiwaki, Takayuki Nakayama, Shigeki Saito, Hiroki Mizuno, Takenori Ozaki, Yoshiyuki Takahashi, Shoichi Maruyama, Tetsuya Nishida, Makoto Murata, Seiji Kojima, Tomoki Naoe

    International journal of hematology   Vol. 96 ( 3 ) page: 295 - 300   2012.9

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    We have demonstrated that adipose tissue-derived mesenchymal stem cells (ADSCs) from mice are capable of reconstituting the hematopoietic microenvironment, and facilitate hematopoiesis more effectively than bone marrow-derived mesenchymal stem cells (BMSCs) in mouse. The ready accessibility of fat tissue rich in MSCs and the higher hematopoiesis-supporting capacities of ADSCs suggest that ADSCs might represent a new therapeutic modality for the regeneration of impaired hematopoiesis. As a further step towards their use in clinical practice, we established human BMSCs and ADSCs from healthy volunteers of similar age, and compared their proliferation capacities, hematopoiesis-supporting properties, and safety. In vitro cell proliferation studies revealed that ADSCs have a higher population doubling number than BMSCs. In vitro co-culture assays showed that ADSCs not only support human CD34(+) peripheral blood stem cells (PBSCs), but also yield significantly more non-adherent hematic cells than BMSCs. In vitro progenitor assays revealed that ADSCs promote a higher frequency of early progenitors than do BMSCs. Interestingly, BM cellularity in irradiated mice that had received ADSCs tended to be higher than that of mice treated with BMSCs. When MSCs were injected into the BM cavity of tibiae, we observed no evidence of MSC-induced toxicity either during or after treatment. In addition, no microscopic abnormalities were observed in the bone marrow and major organs.

    DOI: 10.1007/s12185-012-1140-8

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    PubMed

  186. Phase II study of dose-modified busulfan by real-time targeting in allogeneic hematopoietic stem cell transplantation for myeloid malignancy. Reviewed International journal

    Yachiyo Kuwatsuka, Akio Kohno, Seitaro Terakura, Shigeki Saito, Kazuyuki Shimada, Takahiko Yasuda, Yoshihiro Inamoto, Koichi Miyamura, Masashi Sawa, Makoto Murata, Takahiro Karasuno, Shuichi Taniguchi, Koji Nagafuji, Yoshiko Atsuta, Ritsuro Suzuki, Mariko Fukumoto, Tomoki Naoe, Yoshihisa Morishita

    Cancer science   Vol. 103 ( 9 ) page: 1688 - 94   2012.9

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    We aimed to evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation with targeted oral busulfan (BU) and cyclophosphamide (CY) in a phase II study. Busulfan (1.0 mg/kg) was given initially in six doses. Based on the estimated concentration at steady state after the first dose of BU, subsequent (7th-16th) doses were adjusted to obtain a targeted overall concentration at steady state of 700-900 ng/mL. The primary endpoint was 1-year overall survival (OS). Fifty patients were registered and 46 (median age, 53 years; range, 18-62 years) received planned transplant, including 24 with AML, 16 with myelodysplastic syndrome, and six with CML. Fourteen patients were categorized as standard risk. Nineteen patients received transplant from human leukocyte antigen-identical siblings, 27 from unrelated donors. The BU dose required reduction in 32 patients and escalation in six patients. One-year OS was 65% (95% confidence interval, 50-77%). Cumulative incidence of hepatic sinusoidal obstruction syndrome was 11%. One-year transplant-related mortality was 18%. Both OS and transplant-related mortality were favorable in this study, including patients of older age and with high risk diseases. Individual dose adjustment based on BU pharmacokinetics was feasible and effective in the current phase II study. This trial is registered in the University Hospital Medical Information Network Clinical Trial Registry System (UMIN-CTR, ID:C000000156).

    DOI: 10.1111/j.1349-7006.2012.02342.x

    PubMed

  187. Dexamethasone palmitate successfully attenuates hemophagocytic syndrome after allogeneic stem cell transplantation: macrophage-targeted steroid therapy. Reviewed

    Satoshi Nishiwaki, Takayuki Nakayama, Makoto Murata, Tetsuya Nishida, Kyoko Sugimoto, Shigeki Saito, Tomonori Kato, Hiroki Mizuno, Nobuhiko Imahashi, Aika Seto, Yukiyasu Ozawa, Tatsunori Goto, Daisuke Koyama, Emi Yokohata, Naomi Kubota, Sonoko Kamoshita, Koichi Miyamura, Kimikazu Matsumoto, Masafumi Ito, Tomoki Naoe

    International journal of hematology   Vol. 95 ( 4 ) page: 428 - 433   2012.4

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    Hemophagocytic syndrome (HPS) induced by uncontrolled macrophage activation and subsequent graft failure is a frequent and prominent complication after allogeneic stem cell transplantation (allo-SCT), a cause of severe morbidity and death, and a therapeutic challenge. Liposome-incorporated dexamethasone, dexamethasone palmitate (DP), shows greater efficacy against macrophages as compared to dexamethasone sodium phosphate (DSP). Based on our findings that DP achieves significantly larger decrease than DSP on the viability of primary human macrophages compared in vitro, we tested the effects of DP in patients with HPS. A decrease in number of macrophages in the bone marrow and prevention of engraftment failure were observed in all patients without any severe complications. In conclusion, these data provide a rationale for testing DP as a first-line treatment for patients with HPS after allo-SCT.

    DOI: 10.1007/s12185-012-1023-z

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    PubMed

  188. Escape of leukemia blasts from HLA-specific CTL pressure in a recipient of HLA one locus-mismatched bone marrow transplantation Reviewed

    Tomonori Kato, Seitaro Terakura, Makoto Murata, Kyoko Sugimoto, Miho Murase, Chisako Iriyama, Akihiro Tomita, Akihiro Abe, Momoko Suzuki, Tetsuya Nishida, Tomoki Naoe

    CELLULAR IMMUNOLOGY   Vol. 276 ( 1-2 ) page: 75 - 82   2012

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    A case of leukemia escape from an HLA-specific cytotoxic T lymphocyte (CTL) response in a recipient of bone marrow transplantation is presented. Only the expression of HLA-B51, which was a mismatched HLA locus in the graft-versus-host direction, was down-regulated in post-transplant leukemia blasts compared with that in pre-transplant blasts. All CTL clones, that were isolated from the recipient's blood when acute graft-versus-host disease developed, recognized the mismatched B*51:01 molecule in a peptide-dependent manner. The pre-transplant leukemia blasts were lysed by CTL clones, whereas the posttransplant leukemia blasts were not lysed by any CTL clones. The IFN-gamma ELISPOT assay revealed that B*51:01-reactive T lymphocytes accounted for the majority of the total alloreactive T lymphocytes in the blood just before leukemia relapse. These data suggest that immune escape of leukemia blasts from CTL pressure toward a certain HLA molecule can lead to clinical relapse after bone marrow transplantation. (C) 2012 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.cellimm.2012.03.011

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  189. 原発事故にまつわる自己末梢血幹細胞採取論争 Reviewed

    村田誠

    日本医事新報   Vol. 4580   page: 28 - 28   2012

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  190. Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT Reviewed

    M. Murase, T. Nishida, M. Onizuka, Y. Inamoto, K. Sugimoto, N. Imahashi, M. Murata, K. Miyamura, Y. Kodera, H. Inoko, T. Naoe

    BONE MARROW TRANSPLANTATION   Vol. 46 ( 11 ) page: 1444 - 1449   2011.11

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    CTLA-4 is a negative regulator of activated T cells and the association of CTLA-4 polymorphisms with autoimmune diseases and transplant outcome has been reported. We evaluated the effect of donor CTLA-4 polymorphisms on outcome after allogeneic hematopoietic SCT (HSCT). We analyzed 147 Japanese HLA-matched sibling recipients and their donors who had undergone allogeneic HSCT. Genotyping of three single-nucleotide polymorphisms in CTLA-4 (-318, +49, CT60) was performed using TaqMan-PCR. According to the international HapMap database, only these three CTLA-4 haplotypes, classified as C-G-G, C-A-A and T-A-G, are present in the Japanese population. In this study, percentage expression of the C-G-G, C-A-A and T-A-G haplotypes was 59.5, 30.6 and 9.9%, respectively. Recipients of the C-A-A haplotype donor showed a significantly lower risk of relapse (HR: 0.54, 95% CI: 0.30-0.97, P = 0.040) and a trend toward higher OS (HR: 0.61, 95% CI: 0.36-1.0, P = 0.054) than did recipients of a donor without the C-A-A haplotype. The presence or absence of the C-A-A haplotype did not affect GVHD or non-relapse mortality. As the presence of the C-A-A haplotype reduced relapse risk and improved survival after allogeneic HSCT, this CTLA-4 haplotype may provide useful information for donor selection. Bone Marrow Transplantation (2011) 46, 1444-1449; doi:10.1038/bmt.2010.319; published online 20 December 2010

    DOI: 10.1038/bmt.2010.319

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  191. Irrespective of CD34 expression, lineage-committed cell fraction reconstitutes and re-establishes transformed Philadelphia chromosome-positive leukemia in NOD/SCID/IL-2R gamma c(-/-) mice Reviewed

    Tanizaki Ryohei, Nomura Yuka, Miyata Yasuhiko, Minami Yosuke, Abe Akihiro, Hanamura Akitoshi, Sawa Masashi, Murata Makoto, Kiyoi Hitoshi, Matsushita Tadashi, Naoe Tomoki

    CANCER SCIENCE   Vol. 101 ( 3 ) page: 631 - 638   2010.3

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    DOI: 10.1111/j.1349-7006.2009.01440.x

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  192. Donor single nucleotide polymorphism in the CCR9 gene affects the incidence of skin GVHD Reviewed

    Inamoto Y., Murata M., Katsumi A., Kuwatsuka Y., Tsujimura A., Ishikawa Y., Sugimoto K., Onizuka M., Terakura S., Nishida T., Kanie T., Taji H., Iida H., Suzuki R., Abe A., Kiyoi H., Matsushita T., Miyamura K., Kodera Y., Naoe T.

    BONE MARROW TRANSPLANTATION   Vol. 45 ( 2 ) page: 363 - 369   2010.2

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    DOI: 10.1038/bmt.2009.131

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  193. CTL Clones Isolated from an HLA-Cw-Mismatched Bone Marrow Transplant Recipient with Acute Graft-Versus-Host Disease Reviewed

    Sugimoto Kyoko, Murata Makoto, Terakura Seitaro, Naoe Tomoki

    JOURNAL OF IMMUNOLOGY   Vol. 183 ( 9 ) page: 5991 - 5998   2009.11

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    DOI: 10.4049/jimmunol.0804310

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  194. Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy Reviewed

    Abe Akihiro, Minami Yosuke, Hayakawa Fumihiko, Kitamura Kunio, Nomura Yuka, Murata Makoto, Katsumi Akira, Kiyoi Hitoshi, Jamieson Catriona H. M., Wang Jean Y. J., Naoe Tomoki

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 88 ( 5 ) page: 471 - 475   2008.12

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    DOI: 10.1007/s12185-008-0221-1

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  195. Donor cell leukemia after allogeneic peripheral blood stem cell transplantation: a case report and literature review Reviewed

    Murata Makoto, Ishikawa Yuichi, Ohashi Haruhiko, Terakura Seitaro, Ozeki Kazutaka, Kiyoi Hitoshi, Naoe Tomoki

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 88 ( 1 ) page: 111 - 115   2008.7

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    DOI: 10.1007/s12185-008-0094-3

    Web of Science

  196. Decreased risk of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation in patients with the 5,10-methylenetetrahydrofolate reductase 677TT genotype Reviewed

    Sugimoto Kyoko, Murata Makoto, Onizuka Makoto, Inamoto Yoshihiro, Terakura Seitaro, Kuwatsuka Yachiyo, Oba Taku, Miyamura Koichi, Kodera Yoshihisa, Naoe Tomoki

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 87 ( 5 ) page: 451 - 458   2008.6

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s12185-008-0061-z

    Web of Science

  197. Potential role of a mismatched HLA-Specific CTL clone developed pre-transplant in graft rejection following cord blood transplantation Reviewed

    Narimatsu Hiroto, Murata Makoto, Terakura Seitaro, Sugimoto Kyoko, Naoe Tomoki

    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION   Vol. 14 ( 4 ) page: 397 - 402   2008.4

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbmt.2008.01.001

    Web of Science

  198. Long-term outcome after bone marrow transplantation for aplastic anemia using cyclophosphamide and total lymphoid irradiation as conditioning regimen Reviewed

    Inamoto Yoshihiro, Suzuki Ritsuro, Kuwarsuka Yachiyo, Yasuda Takahiko, Takahashi Taro, Tsujimura Akane, Sugimoto Kyoko, Oba Taku, Terakura Seitaro, Atsuta Yoshiko, Murata Makoto, Ito Masafumi, Kodera Yoshihisa, Miyamura Koichi

    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION   Vol. 14 ( 1 ) page: 43 - 49   2008.1

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbmt.2007.06.015

    Web of Science

  199. 移植医療と組織適合性 同種造血幹細胞移植におけるマイナー組織適合性抗原の臨床的意義 Reviewed

    村田 誠

    MHC: Major Histocompatibility Complex   Vol. 14 ( 2 ) page: 177 - 189   2007.8

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    Language:Japanese   Publisher:日本組織適合性学会  

    マイナー組織適合性抗原とは、患者細胞表面のHLA上に提示される細胞内タンパク由来のペプチドのうち、遺伝子多型により患者とドナー間で異なるアミノ酸配列をもち、非自己のTリンパ球に認識されるものをいう。ヒトでは20数個のマイナー組織適合性抗原が分子レベルで同定されている。マイナー組織適合性抗原に対するTリンパ球応答は、HLA一致ドナー同種造血幹細胞移植後の移植片対宿主病の発症や移植片対腫瘍効果の発現に関与している。(著者抄録)

  200. Successful second cord blood transplantation using fludarabine and cyclophosphamide as a preparative regimen for graft rejection following reduced-intensity cord blood transplantation Reviewed

    Mizutani E., Narimatsu H., Murata M., Tomita A., Kiyoi H., Naoe T.

    BONE MARROW TRANSPLANTATION   Vol. 40 ( 1 ) page: 85 - 87   2007.7

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/sj.bmt.1705684

    Web of Science

  201. A single minor histocompatibility antigen encoded by UGT2B17 and presented by human leukocyte antigen-A*2902 and -B*4403 Reviewed

    Terakura Seitaro, Murata Makoto, Warren Edus H., Sette Alessandro, Sidney John, Naoe Tomoki, Riddell Stanley R.

    TRANSPLANTATION   Vol. 83 ( 9 ) page: 1242 - 1248   2007.5

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1097/01.tp.0000259931.72622.d1

    Web of Science

  202. Successful umbilical cord blood transplantation using a reduced-intensity preparative regimen without total body irradiation and tacrolimus plus methotrexate for prophylaxis of graft-versus-host disease in a patient with adult T-cell leukemia/lymphoma Reviewed

    Narimatsu Hiroto, Murata Makoto, Sugimoto Kyoko, Terakura Seitaro, Kinoshita Tomohiro, Naoe Tomoki

    LEUKEMIA & LYMPHOMA   Vol. 48 ( 4 ) page: 841 - 843   2007

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1080/10428190701191332

    Web of Science

  203. 隣接しない二つのペプチド断片が順序を入れ替えて結合しつくられるマイナー抗原 Reviewed

    村田誠

      Vol. 6   page: 78 - 79   2007

  204. High titer of ADAMTS13 inhibitor associated with thrombotic microangiopathy of the gut and skeletal muscle after allogeneic hematopoietic stem cell transplantation Reviewed

    Adachi Tatsuya, Matsushita Tadashi, Ichihashi Ryoichi, Hirashima Kanji, Ito Masafumi, Inukai Akira, Yokozawa Toshiya, Nishida Tetsuya, Murata Makoto, Hayashi Mutsuharu, Katsumi Akira, Kojima Tetsuhito, Saito Hidehiko, Naoe Tomoki

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 83 ( 5 ) page: 415 - 419   2006.6

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1532/IJH97.05157

    Web of Science

  205. Mutations of N-RAS, FLT3 and p53 genes are not involved in the development of acute leukemia transformed from myeloproliferative diseases with JAK2 mutation Reviewed

    Suzuki M., Abe A., Kiyoi H., Murata M., Ito Y., Shimada K., Morishita Y., Kinoshita T., Naoe T.

    LEUKEMIA   Vol. 20 ( 6 ) page: 1168 - 1169   2006.6

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/sj.leu.2404186

    Web of Science

  206. Stable engraftment after a conditioning regimen with fludarabine and melphalan for bone marrow transplantation from an unrelated donor Reviewed

    Inamoto Y, Oba T, Miyamura K, Terakura S, Tsujimura A, Kuwatsuka Y, Tokunaga M, Kasai M, Murata M, Naoe T, Kodera Y

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 83 ( 4 ) page: 356 - 362   2006.5

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1532/IJH97.05168

    Web of Science

  207. Micafungin, a novel antifungal agent, as empirical therapy in acute leukemia patients with febrile neutropenia Reviewed

    Yanada Masamitsu, Kiyoi Hitoshi, Murata Makoto, Suzuki Momoko, Iwai Masanori, Yokozawa Toshiya, Baba Hisashi, Emi Nobuhiko, Naoe Tomoki

    INTERNAL MEDICINE   Vol. 45 ( 5 ) page: 259 - 264   2006

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.2169/internalmedicine.45.1498

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  208. Identification and frequency of a new HLA-A allele, A*030104 Reviewed

    Murata M, Emi N, Izumisawa Y, Inaki A, Saitoh M, Naoe T

    TISSUE ANTIGENS   Vol. 65 ( 4 ) page: 391 - 392   2005.4

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1399-0039.2005.00383.x

    Web of Science

  209. ドナー細胞での遺伝子欠損により抗原性をもつマイナー抗原UGT2B17 Reviewed

    村田誠

    分子細胞治療   Vol. 3   page: 488 - 489   2004

  210. Apoptotic cytotoxic effects of a histone deacetylase inhibitor, FK228, on malignant lymphoid cells Reviewed

    Murata M, Towatari M, Kosugi H, Tanimoto M, Ueda R, Saito H, Naoe T

    JAPANESE JOURNAL OF CANCER RESEARCH   Vol. 91 ( 11 ) page: 1154 - 1160   2000.11

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    Publishing type:Research paper (scientific journal)  

    Web of Science

  211. 本邦における血縁者間同種末梢血幹細胞移植の全国調査:現状と問題点 Reviewed

    原田 実根, 竹中 克斗, 中尾 真二, 青墳 信之, 沢田 仁, 品川 克至, 笠井 正晴, 井関 徹, 村田 誠, 岡本 真一郎, 兵頭 英出夫, 小寺 良尚

    臨床血液   Vol. 40 ( 11 ) page: 1160 - 1167   1999.11

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

    わが国での同種末梢血幹細胞移植(allo-PBSCT)の現状について全国調査を行った.年齢の中央値は37歳で,対象疾患はAML43例,CML19例,ALL14例,MDS14例,その他13例であった.ドナーはHLA適合同胞が85%を占めた.移植CD34陽性細胞数は,中央値5.3×10^6/kgで,血液学的回復は好中球500/μl以上の回復に中央値13日,血小板20,000/μl以上の回復に中央値13日であった.移植後100日以内の移植関連死亡は16.1%に見られた.急性GVHDは,II〜IV度が37.4%,III〜IVが16.2%に見られ,慢性GVHDは68.6%に見られた

  212. 同種骨髄移植におけるシクロスポリンMEPCの効果および安全性に関する検討 Reviewed

    村田誠, 林真, 宮脇修一, 加藤俊一, 森島泰雄, 浅野茂隆, 長尾大, 小寺良尚

    今日の移植   Vol. 12   page: 87 - 98   1999

  213. Unrelated donor bone marrow transplantation in Japanese patients is facilitated by the national marrow donor program of the United States Reviewed

    M Murata, M Haneda, T Nishida, T Kanie, M Hamaguchi, S Minami, Y Kodera

    TRANSPLANTATION PROCEEDINGS   Vol. 30 ( 1 ) page: 150 - 152   1998.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE INC  

    Web of Science

  214. 単一施設における非血縁者間骨髄移植と同胞間骨髄移植の比較検討 Reviewed

    村田 誠, 蟹江 匡治, 田地 浩史

    臨床血液   Vol. 37 ( 11 ) page: 1245 - 1252   1996.11

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

    同時期に施行された非血縁者間骨髄移植(UR-BMT)28例と,HLA一致同胞間骨髄移植(SB-BMT)75例を比較した.SB-BMTは全例生着したが,UR-BMTは重症再生不良性貧血(SAA)1例に拒絶を認めた.grade III以上acute GVHDの発症率はUR-BMT 19%, SB-BMT 0%とUR-BMTで高率だった.しかし,grade II以下の症例の生存率は62% vs 65%で同等だった.白血病の無病生存率はstandard riskがUR-BMT 76%, SB-BMT 66%, high riskが30%, 31%で有意差はなかった.年齢別生存率は30歳代がUR-BMT 44%, SB-BMT 76%, 40歳以上が0%, 45%でいずれもUR-BMTで低率だった.死因はウイルス感染症がUR-BMTのみにみられた

  215. 寛解導入不能の急性骨髄性白血病(M5a)に対し米国骨髄バンクからの骨髄移植により寛解に至った1例 Reviewed

    村田 誠, 蟹江 匡治, 田地 浩史

    日常診療と血液   Vol. 6 ( 11 ) page: 1340 - 1344   1996.10

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    Language:Japanese   Publisher:(株)医薬ジャーナル社  

    41歳男.4回に及ぶ寛解導入療法に全く反応ぜず多剤耐性を示したAMLに対し,血縁,日本骨髄バンクのいずれにもドナーを見出すことできず,米国骨髄バンクに発録した.短期間にドナーを得,登録59日後に同種骨髄移植を施行し,寛解を得た.80日頃より皮膚乾燥,口腔粘膜扁平苔癬様病変を認め,皮膚,口腔粘膜生検より慢性GVHDと診断した.増悪,再発の徴候なく118日目に退院した.225日目に血球数72,100/ul(芽球67%)と再発を確認,再入院となった.免疫抑制剤の早期漸減,化学療法を施行したが,311日目に肺炎を合併し死亡した

  216. 成人急性白血病第一寛解期での骨髄移植と化学療法の比較検討 Reviewed

    鈴木律朗, 飯田浩充, 田地浩史, 村田誠, 杉原卓朗, 南三郎, 小寺良尚

    臨床血液   Vol. 37   page: 1362 - 1370   1996

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Books 14

  1. 骨髄線維症 〜分子病態の解明から新規薬物治療薬の開発まで〜

    村田 誠、他( Role: Joint author)

    医薬ジャーナル社  2016 

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    Language:Japanese Book type:Scholarly book

  2. 日本臨床 増刊号 白血病学(下)ー最新の基礎, 臨床研究ー

    村田 誠、他( Role: Sole author)

    日本臨床社  2016 

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    Language:Japanese Book type:Scholarly book

  3. 日本臨床 増刊号 白血病学(下)ー最新の基礎, 臨床研究ー

    村田 誠、他( Role: Sole author)

    日本臨床社  2016 

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    Language:Japanese Book type:Scholarly book

  4. 今日の治療指針2016年版ー私はこう治療している

    村田 誠、他( Role: Joint author)

    医学書院  2016 

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    Language:Japanese Book type:Scholarly book

  5. 血液科研修ノート

    村田 誠、他( Role: Joint author)

    診断と治療社  2016 

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    Language:Japanese Book type:Scholarly book

  6. EBM血液疾患の治療2015-2016

    村田 誠、他( Role: Joint author)

    中外医薬社  2014 

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    Language:Japanese

  7. 白血病と言われたら

    村田 誠、他( Role: Joint author)

    特定非営利活動法人 全国骨髄バンク推進連絡協議会  2014 

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    Language:Japanese

  8. インフォームドコンセントのための図説シリーズ -GVHD(移植片対宿主病)と造血細胞移植-

    村田 誠、他( Role: Joint author)

    医薬ジャーナル社  2014 

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    Language:Japanese

  9. みんなに役立つGVHDの基礎と臨床

    村田 誠、他( Role: Joint author)

    医薬ジャーナル社  2013 

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    Language:Japanese

  10. 診療ガイドラインUP-TO-DATE

    村田 誠、直江知樹( Role: Joint author)

    メディカルレビュー社  2010 

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    Language:Japanese

  11. GVHD予防・治療マニュアル

    村田 誠、他( Role: Joint author)

    南江堂  2005 

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    Language:Japanese

  12. Non-myeloablative transplants for malignant disease

    Riddell SR, Murata M, Bryant S, Warren EH( Role: Joint author)

    American Society of Hematology  2001 

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    Language:English

  13. 造血細胞移植マニュアル(第二版)

    村田 誠、他( Role: Joint author)

    日本医学館  1998 

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    Language:Japanese

  14. Germfree life and its ramifications

    Kodera Y, Murata M, Kanie T, Nakashima J, Taji H, Nakayama Y, Hamaguchi M, Minami S.( Role: Joint author)

    ISG Publishing Committee  1996 

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    Language:English

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Presentations 17

  1. Transplantation for primary myelofibrosis using bone marrow, peripheral blood and umbilical cord blood: a retrospective analysis of the Japan Society for Hematopoietic Cell Transplantation International conference

    Murata M, Nishida T, Taniguchi S, Ohashi K, Ogawa H, Fukuda T, Morishima Y, Nagamura-Inoue T, Sakamaki H, Atsuta Y, Suzuki R, Naoe T

    The 39th Annual Meeting of the European Society for Blood and Marrow Transplantation 

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    Event date: 2013.4

    Language:English   Presentation type:Poster presentation  

    Country:United Kingdom  

  2. Clinical Factors Predicting the Response of Acute Graft-Versus-Host Disease to Corticosteroid Therapy International conference

    Murata M, Nakasone H, Kanda J, Nakane T, Furukawa T, Fukuda T, Taniguchi S, Mori T, Eto T, Morishima Y, Nagamura-Inoue T, Yabe H, Atsuta Y, Sakamaki H, Suzuki R

    The 54rd Annual Meeting of the American Society of Hematology 

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    Event date: 2012.12

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  3. Leukaemia escape from HLA-specific T-lymphocyte pressure in a recipient of HLA one locus-mismatched BMT International conference

    Murata M, Kato T, Terakura S, Sugimoto K, Nishida T, Naoe T

    The 38th Annual Meeting of the European Group for Blood and Marrow Transplantation 

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    Event date: 2012.4

    Language:English   Presentation type:Poster presentation  

    Country:Switzerland  

  4. Current status of acute graft-versus-host disease prophylaxis in Japan: Retrospective comparison of cyclosporine plus methotrexate versus tacrolimus plus methotrexate by donor source International conference

    Sakai R, Taguri M, Oshima K, Mori T, Ago H, Adachi S, Morita S, Taniguchi S, Fukuda T, Ohashi K, Eto T, Morishima Y, Nagamura-Inoue T, Sakamaki H, Atsuta Y, Murata M

    The 38th Annual Meeting of the European Group for Blood and Marrow Transplantation 

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    Event date: 2012.4

    Language:English   Presentation type:Oral presentation (general)  

    Country:Switzerland  

  5. The effect of sex mismatch on outcome in allogeneic hematopoietic stem cell transplantation International conference

    Oshima K, Taniguchi S, Fukuda T, Kakihana K, Eto T, Ikegame K, Morishima Y, Nagamura T, Sakamaki H, Atsuta Y, Murata M

    2012 BMT Tandem Meetings 

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    Event date: 2012.2

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  6. Correlation of Serum IL-6 Level with Exhaustion of Cytomegalovirus-specific T Cells After Hematopoietic Stem Cell Transplantation International conference

    Kato T, Nishida T, Murase M, Ito Y, Murata M, Naoe T

    The 53rd Annual Meeting of the American Society of Hematology 

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    Event date: 2011.12

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  7. Mesenchymal Stem Cells As a Treatment for Steroid-Resistant Acute Graft Versus Host Disease (aGVHD); A Multicenter Phase I/II Study International conference

    Ozawa Y, Goto T, Ohashi K, Murata M, Eto T, Kobayashi N, Taniguchi S, Imamura M, Ando K, Kato K, Mori T, Teshima T, Mori M, Muroi K, Miyamura K, Ozawa K

    The 53rd Annual Meeting of the American Society of Hematology 

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    Event date: 2011.12

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  8. Leukemia Escape From HLA-Specific T Lymphocyte Pressure in a Recipient of HLA One Locus-Mismatched Bone Marrow Transplantation International conference

    Kato T, Murata M, Terakura S, Sugimoto K, Murase M, Nishida T, Naoe T

    The 53rd Annual Meeting of the American Society of Hematology 

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    Event date: 2011.12

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  9. Engraftment rate and kinetics following umbilical cord blood transplantation is critically affected by CD34+ progenitor cell dose and CD8+ T-cell dose complementary International conference

    The 33rd annual meeting of the European Group for Blood and Marrow Transplantation 

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    Event date: 2007.3

    Language:English   Presentation type:Oral presentation (general)  

    Country:France  

  10. Short-term methotrexate could reduce early immune reaction and improve non-relapse mortality in umbilical cord blood transplantation for adult patients International conference

    The 11th congress of the Asia Pacific Bone Marrow Transplantation 

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    Event date: 2006.10

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  11. A single minor histocompatibility antigen AELLNIPFLY encoded by UGT2B17 is presented by HLA-A*2902, B*4402 and B*4403 International conference

    2006 BMT Tandem Meetings 

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    Event date: 2006.2

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:United States  

  12. Human minor histocompatibility antigens: Targets of graft-versus-host disease and graft-versus-leukemia responses International conference

    The 10th congress of the International Society of Hematology, Asian-Pacific Division 

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    Event date: 2004.9

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  13. Differential expression due to a gene deletion: a novel mechanism for generating a minor histocompatibility antigen International conference

    The 44th annual meeting of the American Society of Hematology 

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    Event date: 2002.12

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  14. Minor histocompatibility antigens - Major targets of graft-versus-leukemia responses International conference

    The 43rd annual meeting of the American Society of Hematology 

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    Event date: 2001.12

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:United States  

  15. Myeloid/NK cell precursor acute leukemia is a distinct subtype of AML M0 International conference

    The 43rd annual meeting of the American Society of Hematology 

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    Event date: 2001.12

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  16. A novel HLA-A*2902-restricted human minor histocompatibility antigen is encoded by an alternative open reading frame International conference

    The 43rd annual meeting of the American Society of Hematology 

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    Event date: 2001.12

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  17. Allogeneic transplantation of peripheral blood stem cells in Japan

    The 3rd Nagoya International Blood and Marrow Transplantation Symposium 

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    Event date: 1999.5

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

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Research Project for Joint Research, Competitive Funding, etc. 18

  1. 間葉系幹細胞を利用する新しいGVHD予防法の開発と次世代シークエンサーによる遺伝子情報に基づく新しいドナー選択法の開発に関する研究

    2017.4 - 2020.3

    免疫アレルギー疾患等実用化研究事業 

    村田 誠

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    Grant type:Competitive

  2. インターロイキン2の免疫抑制作用を活用する新しい免疫制御療法の開発

    2015.4 - 2017.3

    科学技術振興調整費 

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    Grant type:Competitive

  3. 免疫遺伝情報に基づく非血縁移植統合データベースの構築と最適なドナー・さい帯血の選択

    2014.4 - 2017.3

    科学技術振興調整費 

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    Grant type:Competitive

  4. 本邦における造血細胞移植一元化登録研究システム及び研究データ質管理システムの確立

    2014.4 - 2015.3

    科学技術振興調整費 

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    Grant type:Competitive

  5. 新たな造血幹細胞移植法の開発:生着効率の向上を目指して

    2013.4 - 2016.3

    科学技術振興調整費 

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    Grant type:Competitive

  6. 本邦における造血細胞移植一元化登録研究システムの確立

    2011.4 - 2014.3

    科学技術振興調整費 

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    Grant type:Competitive

  7. 非血縁移植のドナー・移植細胞源の選択に有用なHLAと非HLA遺伝子の選択アルゴリズムの確立

    2011.4 - 2014.3

    科学技術振興調整費 

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    Grant type:Competitive

  8. 肉腫及び膠芽腫等の難治性がんに対する(個別化)がんワクチン療法等の確立

    2011.4 - 2013.3

    がん研究開発費 

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    Grant type:Competitive

  9. 臍帯血を用いた骨髄内移植療法の開発

    2010.4 - 2013.3

    科学技術振興調整費 

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    Grant type:Competitive

  10. 科学的・行政的視点を踏まえた、がん細胞免疫療法

    2010.4 - 2011.3

    がん研究開発費 

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    Grant type:Competitive

  11. 組織適合性に基づく非血縁同種造血幹細胞の成績向上に関する研究

    2008.4 - 2011.3

    科学技術振興調整費 

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    Grant type:Competitive

  12. 各種がん免疫療法の開発と臨床的有効性の評価に関する研究

    2008.4 - 2010.3

    がん研究助成金 

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    Grant type:Competitive

  13. ヒト・マイナー組織適合性抗原の同定およびその臨床的意義に関する研究

    2006.4 - 2007.3

  14. Immunobiology of GVL responses and GVHD

    2006.4 - 2007.3

    International Cooperative Research 

  15. 同種造血幹細胞移植における遺伝子多型の与える影響に関する研究

    2005.4 - 2008.3

    科学技術振興調整費 

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    Grant type:Competitive

  16. ヒト・マイナー組織適合抗原の同定およびその臨床的意義に関する研究

    2004.9 - 2005.3

  17. 同種造血幹細胞移植における同種抗原の同定およびその臨床的意義の解析

    2003.10 - 2005.3

  18. 同種造血幹細胞移植におけるマイナー組織適合性抗原の同定およびその臨床的意義の解析

    2003.10 - 2004.3

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KAKENHI (Grants-in-Aid for Scientific Research) 11

  1. 移植前にGVHD関連T細胞を推定するヒト急性GVHDにおけるT細胞応答の解析

    2018.4 - 2021.3

    科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

  2. 組織浸潤アロT細胞の標的抗原とクロノタイプに着目したGVHDバイオマーカーの開発

    2015.4 - 2018.3

    科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

  3. HLA-DP分子特異的免疫応答の解析:新しい免疫療法開発に向けて

    2011.4 - 2014.3

    科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

  4. 臍帯血移植の生着・拒絶に関与する移植片中および患者末梢血中CD8陽性T細胞の解析

    2008.4 - 2011.3

    科学研究費補助金  基盤研究(C)

    村田 誠

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    Authorship:Principal investigator 

  5. 新規マイナー組織適合性抗原の同定および造血幹細胞移植におけるその臨床的意義の解析

    2005.4 - 2007.3

    科学研究費補助金  若手研究(B)

    村田 誠

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    Authorship:Principal investigator 

  6. ヒト急性GVHDにおける組織残存レシピエントT細胞の機能と臨床的意義の解明

    Grant number:21K08387  2021.4 - 2024.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    村田 誠

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    急性移植片対宿主病(GVHD)は同種造血幹細胞移植における致死的合併症の一つである。急性GVHDは生着したドナーT細胞が患者組織を傷害することにより発症すると考えられている。一方、最近レシピエントT細胞が移植後もGVHD組織に残存することが報告された。しかし、それらレシピエントT細胞とGVHD発症との関わりについては十分明らかにされていない。本研究では、ヒト急性GVHD組織残存レシピエントT細胞を詳細に解析し、その解析結果とGVHD重症度や治療反応性など臨床経過との関連を明らかにすることで、組織残存レシピエントT細胞の臨床的意義を解明する。

  7. ゲノム情報により造血幹細胞移植の最適化を目指す研究

    2020.4 - 2023.3

    日本医療研究開発機構  移植医療技術開発研究事業 

    村田 誠

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    Authorship:Principal investigator 

  8. 臍帯血移植の生着促進をめざした間葉系幹細胞の骨髄内輸注に関する臨床研究

    2018.4 - 2020.3

    日本輸血・細胞治療学会  臨床研究支援事業研究補助金 

    村田 誠

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    Authorship:Principal investigator 

  9. 次世代シークエンサーを用いた臨床的意義の高いGVHD関連T細胞の頻度解析

    2016.4 - 2017.3

    公益信託  第24回日本医学会総会記念医学振興基金 

    村田 誠

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    Authorship:Principal investigator 

  10. Analysis of HLA-DP-specific immune responses to develop a novel immunotherapy

    Grant number:23591415  2011 - 2013

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MURATA Makoto

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    Authorship:Principal investigator 

    Grant amount:\5200000 ( Direct Cost: \4000000 、 Indirect Cost:\1200000 )

    The 20-99% of leukemia cells was positive for HLA-DP expression. Twenty-four cytotoxic T cell (CTL) lines were isolated from blood obtained from seven patients who had received HLA-mismatched hematopoietic stem cell transplantation. All CTLs recognized HLA-class I or DR molecules but not DP molecule. Anti-HLA antibodies were detected in blood obtained from eight patients who had received multi-transfusion. All antibodies recognized HLA class I but not class II molecules. In vitro assay using patient serum containing anti-HLA antibody demonstrated that the hematopoietic stem cells were lysed by anti-HLA antibody through ADCC activity. Stimulation of T cells by .221 cells transfected with each HLA-DP cDNA construct is ongoing.

  11. 同種造血幹細胞移植における抗原物質(マイナー組織適合性抗原)の同定およびその臨床的意義の解析

    2003.4 - 2004.3

    財団法人興和生命科学振興財団  研究助成金 

    村田 誠

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    Authorship:Principal investigator 

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Teaching Experience (On-campus) 10

  1. 血液学講義

    2014

  2. 血液学講義

    2013

  3. 生涯健康と医学講座

    2012

  4. 血液学講義

    2012

  5. 血液学講義

    2011

  6. 血液学講義

    2010

  7. 血液学講義

    2009

  8. 臨床腫瘍学講義

    2008

  9. 移植医療講義

    2007

  10. 臨床腫瘍学講義

    2007

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