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

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. (c) 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.