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

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Abstract

To investigate the association between methotrexate (MTX) dosage and engraftment, graft-versus-host disease (GVHD) incidence, and survival in umbilical cord blood transplantation (UCBT), we compared transplant outcomes after UCBT with various GVHD prophylaxis regimens, using registry data with additional data collection. Patients transplanted for acute myeloid leukemia with a calcineurin inhibitor (CNI) and either MTX or mycophenolate mofetil (MMF) combination were selected. In total, 888 single-unit UCBTs (MTX15–10–10, 415; MTX10–7–7, 294; MTX5–5–5, 71; MMF, 108) were included. In multivariate analyses with MTX15–10–10 as the reference, the likelihood of neutrophil and platelet engraftment was significantly worse in the MTX10–7–7 group, and similarly better in MMF group compared with MTX15–10–10. All variables including CyA vs Tac and 4-group GVHD prophylaxis became significant for the risk of grade II–IV acute GVHD in the final multivariate model. We observed significant additional effects of combined MTX dose in the Tac group, which were larger with lower MTX dose and MMF. No significant difference was observed in survival risk among GVHD prophylaxis groups. Despite the potential background differences in the combined CNI and conditioning regimen, we conclude that the recommended GVHD prophylaxis is a combination of CyA plus MTX15–10–10 or Tac plus MMF.

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Acknowledgements

The authors would like to thank all the physicians and data managers at the institutes that contributed valuable data on the transplantation to the Japan Society for Hematopoietic Stem Cell Transplantation (JSHCT) and all the members of the data management committees of the JSHCT. The authors are grateful to Ms. Noriko Mizutani for her excellent help with data management. This study was supported in part by a grant from the Japan Society for the Promotion of Science (JSPS) KAKENHI (18k08351 to ST).

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Authors and Affiliations

  1. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8560, Japan

    Seitaro Terakura & Makoto Murata

  2. Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan

    Yachiyo Kuwatsuka

  3. Department of Hematology, Faculty of Medicine, Hokkaido University, Sapporo, Japan

    Junichi Sugita & Takanori Teshima

  4. Division of Molecular Therapy, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Satoshi Takahashi

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

    Yukiyasu Ozawa

  6. Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan

    Kazutaka Ozeki

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

    Satoshi Yoshioka

  8. Department of Hematology, Osaka City University Hospital, Osaka, Japan

    Hirohisa Nakamae

  9. Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan

    Toshiro Kawakita

  10. Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan

    Masashi Sawa

  11. Division of Hematology and Oncology, Department of Medicine, Kurume University Hospital, Kurume, Japan

    Satoshi Morishige

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

    Yuho Najima

  13. Department of Hematology, National Hospital Organization Sendai Medical Center, Sendai, Japan

    Yuna Katsuoka

  14. Department of Hematology, Chiba University Hospital, Chiba, Japan

    Emiko Sakaida

  15. Department of Transfusion Medicine, Tokyo Metropolitan Tama Medical Center, Fuchu, Japan

    Yasuji Kouzai

  16. Preparation Department, Japanese Red Cross Kinki Block Blood Center, Ibaraki, Japan

    Takafumi Kimura

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

    Tatsuo Ichinohe

  18. Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda

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

    Yoshiko Atsuta

  20. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshiko Atsuta

Authors
  1. Seitaro Terakura
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  2. Yachiyo Kuwatsuka
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  20. Makoto Murata
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  21. Takanori Teshima
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Correspondence to Seitaro Terakura.

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Terakura, S., Kuwatsuka, Y., Sugita, J. et al. Effect of methotrexate dose in graft-versus-host disease prophylaxis after single-unit cord blood transplantation in adult acute myeloid leukemia. Int J Hematol 113, 840–850 (2021). https://doi.org/10.1007/s12185-021-03097-8

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