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Cyclosporine/methotrexate versus tacrolimus/methotrexate with or without anti-thymocyte globulin as GVHD prophylaxis in adult patients with aplastic anemia

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Abstract

The impact of calcineurin inhibitor types and anti-thymocyte globulin (ATG) in conditioning on overall survival (OS) and GVHD-free, relapse-free survival (GRFS) has not yet been analyzed in detail for aplastic anemia. We herein examined 517 adult patients with aplastic anemia who underwent BMT from HLA-matched sibling donors (MSD, n = 255) and unrelated donors (UD, n = 262) and were treated with cyclosporine A (CSA) + methotrexate (MTX) (n = 258) and tacrolimus (TAC) + MTX (n = 259). In total, 330 patients received ATG in conditioning. CSA + MTX versus TAC + MTX did not have a significant impact on acute and chronic GVHD, OS, or GRFS in each donor type. The use of ATG in conditioning reduced the risk of grade II–IV acute GVHD in the MSD and UD cohorts (HR 0.42, P = 0.014, and HR 0.3, P < 0.001, respectively); however, a differential impact on GRFS was identified, namely, better GRFS in MSD recipients (HR 0.56, P = 0.016), but not in UD recipients (HR 1.1, P = 0.657). In conclusion, CSA + MTX and TAC + MTX were similar as GVHD prophylaxis regardless of the donor type, and ATG in conditioning increased GRFS in MSD transplants, but not in UD transplants.

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Acknowledgments

The authors thank all of the clinical physicians and staff members at the collaborating transplantation centers, the JSHCT, the Japan Marrow Donor Program, and the Japanese Data Center for Hematopoietic Cell Transplantation.

Funding

This work was financially supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development (AMED) under grant 18ek0510023h0002.

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Authors and Affiliations

  1. Department of Hematology and Rheumatology, Tohoku University Hospital, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan

    Yasushi Onishi

  2. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Takehiko Mori & Jun Kato

  3. Division of Transfusion Medicine, Kanazawa University Hospital, Kanazawa, Japan

    Hirohito Yamazaki

  4. Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Matsuyama, Japan

    Katsuto Takenaka

  5. Department of Hematology, Nippon Medical School, Tokyo, Japan

    Hiroki Yamaguchi

  6. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Naoki Shingai

  7. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Yukiyasu Ozawa

  8. Division of Cell Therapy, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    Hiroatsu Iida

  9. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    Shuichi Ota

  10. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo, Japan

    Naoyuki Uchida

  11. Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Toshihiro Miyamoto

  12. Department of Hematology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan

    Yuta Katayama

  13. Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan

    Satoshi Yoshioka

  14. Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Japan

    Makoto Onizuka

  15. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    Tatsuo Ichinohe

  16. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    Yoshiko Atsuta

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  1. Yasushi Onishi
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  2. Takehiko Mori
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on behalf of the Adult Aplastic Anemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Contributions

YO, TM, HY, KT, and HY designed the study. YO performed statistical analyses and wrote the manuscript. NS, YO, HI, SO, NU, TM, YK, JK, and SY provided patient data. MO, TI, and YA collected patient data. All authors interpreted data and reviewed and approved the final manuscript.

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Correspondence to Yasushi Onishi.

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Onishi, Y., Mori, T., Yamazaki, H. et al. Cyclosporine/methotrexate versus tacrolimus/methotrexate with or without anti-thymocyte globulin as GVHD prophylaxis in adult patients with aplastic anemia. Ann Hematol 100, 217–228 (2021). https://doi.org/10.1007/s00277-020-04290-1

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