Impact of methotrexate‐dosing regimens for <scp>GVHD</scp> prophylaxis on clinical outcomes of <scp>HLA</scp> ‐matched allogeneic <scp>HSCT</scp>
Severe graft-versus-host disease (GVHD) remains a major complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT), necessitating optimal immunosuppressive strategies. This retrospective study used data from the Japanese Transplant Registry Unified Management Program to compare three methotrexate (MTX)-dosing regimens for GVHD prophylaxis in patients undergoing human leucocyte antigen (HLA)-matched allo-HSCT: a low-dose 3-day regimen (Ld3:10 mg/m<sup>2</sup> on day 1, 7 mg/m<sup>2</sup> on days 3 and 6), a low-dose 4-day regimen (Ld4: Ld3 with an additional 7 mg/m<sup>2</sup> on day 11) and an original-dose 3-day regimen (Od3: 15 mg/m<sup>2</sup> on day 1, 10 mg/m<sup>2</sup> on days 3 and 6). Among 2537 analysed patients, Ld3 was the most commonly used regimen. Multivariate analyses showed no significant differences in the cumulative incidence of grade II-IV acute GVHD among regimens. However, Od3 was associated with an increased risk of grade III-IV acute GVHD, and Ld4 was linked to delayed neutrophil engraftment. This study is the first large-scale retrospective analysis of the impact of different MTX-dosing regimens on the outcomes of HLA-matched allo-HSCT, providing valuable insights into optimal MTX-dosing strategies in clinical practice.
Authors
- Masatsugu Tanaka (ORCID: https://orcid.org/0000-0001-8814-230X)
- Takahiro Fukuda
- Yoshinobu Kanda (ORCID: https://orcid.org/0000-0002-4866-9307)
- Yuta Hasegawa (ORCID: https://orcid.org/0000-0002-9925-2093)
- Noboru Asada (ORCID: https://orcid.org/0000-0001-7322-5460)
- Noriko Doki (ORCID: https://orcid.org/0000-0002-8661-3179)
- Tadakazu Kondo (ORCID: https://orcid.org/0000-0002-8959-6271)
- Tomotaka Suzuki (ORCID: https://orcid.org/0000-0001-5694-8501)
- Yoshiko Atsuta (ORCID: https://orcid.org/0000-0003-4404-2870)
- Tomoyasu Jo (ORCID: https://orcid.org/0000-0001-9381-0421)
- Shuichi Ota (ORCID: https://orcid.org/0000-0002-3631-244X)
- Kentaro Serizawa
- Junya Kanda (ORCID: https://orcid.org/0000-0002-6704-3633)
- Makoto Yoshimitsu (ORCID: https://orcid.org/0000-0002-5935-0385)
- Yasushi Onishi (ORCID: https://orcid.org/0000-0003-0032-6994)
- Kota Yoshifuji (ORCID: https://orcid.org/0009-0000-9206-3137)
- Masashi Sawa
- Tetsuya Nishida
Institutions
- Kagoshima University (JP)
- Tokyo Institute of Technology (JP)
- Jichi Medical University (JP)
- Aichi Medical University (JP)
- Kyoto University (JP)
- Kanagawa Prefectural Hospital Organization (JP)
- Tokyo Metropolitan Komagome Hospital (JP)
- Nagoya City University (JP)
- National Cancer Centre Japan (JP)
- Tokyo Institute of Psychiatry (JP)
- Tohoku University Hospital (JP)
- Okayama University Hospital (JP)
- Sapporo Hokuyu Hospital (JP)
- Japanese Red Cross Nagoya Daiichi Hospital (JP)
- Hokkaido University Hospital (JP)
- Anjo Kosei Hospital (JP)
- The Japanese Data Center for Hematopoietic Cell Transplantation (JP)
- Kobe City Medical Center General Hospital (JP)
- Jichi Medical University Saitama Medical Center (JP)
- Kindai University (JP)
Publication Details
- Journal
- British Journal of Haematology
- Published
- 2025-10-19
- DOI
- https://doi.org/10.1111/bjh.70213
- Primary Topic
- Hematopoietic Stem Cell Transplantation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Pfizer
- Sanofi
- Nippon Shinyaku
- Astellas Pharma
- Chugai Pharmaceutical
- Japan Society for the Promotion of Science