Comparison of methotrexate dosing protocols for graft-versus-host disease prophylaxis after unrelated hematopoietic stem cell transplantation

Naokazu Nakamura; Junya Kanda; Tadakazu Kondo; Toshiyuki Kitano; Takashi Ikeda; Kazunori Imada; Ryosuke Takaya; Tomoyo Kubo; Satoshi Mitsuyuki; Satoko Oka; Akihito Yonezawa; Tomoharu Takeoka; Takashi Akasaka; Masakatsu Hishizawa; Kazuhiro Yago; Hiroko Tsunemine; Mitsumasa Watanabe; Mitsuru Itoh; Akifumi Takaori-Kondo; Kyoto Stem Cell Transplantation Group (KSCTG)

doi:10.1016/j.jcyt.2024.11.009

Comparison of methotrexate dosing protocols for graft-versus-host disease prophylaxis after unrelated hematopoietic stem cell transplantation

Cytotherapy. 2024 Nov 17:S1465-3249(24)00935-6. doi: 10.1016/j.jcyt.2024.11.009. Online ahead of print.

Authors

Naokazu Nakamura¹, Junya Kanda², Tadakazu Kondo³, Toshiyuki Kitano⁴, Takashi Ikeda⁵, Kazunori Imada⁶, Ryosuke Takaya⁷, Tomoyo Kubo⁸, Satoshi Mitsuyuki⁸, Satoko Oka⁹, Akihito Yonezawa¹⁰, Tomoharu Takeoka¹¹, Takashi Akasaka¹², Masakatsu Hishizawa¹³, Kazuhiro Yago¹⁴, Hiroko Tsunemine¹⁵, Mitsumasa Watanabe¹⁶, Mitsuru Itoh¹⁷, Akifumi Takaori-Kondo²; Kyoto Stem Cell Transplantation Group (KSCTG)²

Affiliations

¹ Department of Hematology and Oncology, Kyoto University, Kyoto, Japan; Division of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Hematology, Shinko Hospital, Kobe, Japan.
² Department of Hematology and Oncology, Kyoto University, Kyoto, Japan.
³ Department of Hematology and Oncology, Kyoto University, Kyoto, Japan; Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan. Electronic address: tadakazu@kuhp.kyoto-u.ac.jp.
⁴ Department of Hematology, Tazuke Kofukai, Medical Research Institute, Kitano Hospital, Osaka, Japan.
⁵ Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, Shizuoka, Japan.
⁶ Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan.
⁷ Department of Hematology, Kurashiki Central Hospital, Kurashiki, Japan.
⁸ Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan.
⁹ Division of Hematology, Japanese Red Cross Society Wakayama Medical Center, Wakayama, Japan.
¹⁰ Department of Hematology, Kokura Memorial Hospital, Kokura, Japan.
¹¹ Department of Hematology, Japan Red Cross Otsu Hospital, Otsu, Japan.
¹² Department of Hematology, Tenri Hospital, Tenri, Japan.
¹³ Department of Hematology, Kyoto-Katsura Hospital, Kyoto, Japan.
¹⁴ Department of Hematology, Shizuoka General Hospital, Shizuoka, Japan.
¹⁵ Department of Hematology, Shinko Hospital, Kobe, Japan.
¹⁶ Department of Hematology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan.
¹⁷ Department of Hematology, Kyoto City Hospital, Kyoto, Japan.

PMID: 39652019
DOI: 10.1016/j.jcyt.2024.11.009

Abstract

Background aims: Methotrexate (MTX) is used as standard graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation. However, the optimal dosing regimen among the various MTX regimens available remains unclear.

Methods: We used the registration data of Kyoto Stem Cell Transplantation Group to compare six MTX dosing protocols in a multicenter retrospective analysis of 816 cases of unrelated bone marrow or peripheral blood stem cell transplantation.

Results: Our findings indicated increased risks of grade Ⅱ-Ⅳ acute GVHD and extensive chronic GVHD in the cohort given the shortened mini-dose MTX regimen (5 mg/m² infusions on days 1, 3, and 6) compared with patients that received any of the other protocols. In addition, transplantation outcomes did not differ significantly between cohorts according to the inclusion or absence of leucovorin rescue.

Conclusion: The original short-term, reduced short-term, and mini-dose MTX methods were all effective for GVHD prophylaxis. However, omission of the day 11 MTX dose from the mini-dose regimen elevated the risks of grade Ⅱ-Ⅳ acute GVHD and extensive chronic GVHD. Moreover, leucovorin rescue might be ineffective in terms of reducing complications.

Keywords: Allogenic hematopoietic stem cell transplantation; GVHD/relapse-free survival; Graft versus host disease; Methotrexate.