Efficacy of folinic acid rescue following MTX GVHD prophylaxis: Results of a double-blind, randomized, controlled study

Moshe Yeshurun*, Uri Rozovski, Oren Pasvolsky, Ofir Wolach, Ron Ram, Odelia Amit, Tsila Zuckerman, Anat Pek, Maly Rubinstein, Michal Sela-Navon, Pia Raanani, Liat Shargian-Alon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The use of methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis is associated with increased rates of organ-specific toxicities. Despite limited data, the European Society for Blood and Marrow Transplantation-European LeukemiaNet working group recommend the use of folinic acid (FA) rescue to reduce MTX toxicity after allogeneic hematopoietic cell transplantation (allo-HCT). In a multicenter, double-blind, randomized, controlled trial, we explored whether FA rescue reduces MTX-induced toxicity. We enrolled patients undergoing allo-HCT with myeloablative conditioning with peripheral blood stem cell grafts, with GVHD prophylaxis consisting of cyclosporine and MTX. Patients were randomized to receive FA or placebo starting 24 hours after each MTX dose and continuing over 24 hours in 3 to 4 divided doses. The primary end point was the rate of grades 3 and 4 oral mucositis. After enrollment of 52 patients (FA, n 5 28; placebo, n 5 24), preplanned interim analysis revealed similar rates of grade 3 and 4 (46.6% vs 45.8%; P 5 .97) and grades 1 to 4 (83.3% vs 77.8%; P 5 .65) oral mucositis. With a median follow-up of 17 (range, 4.5-50) months, there was no difference in the rates of acute and chronic GVHD, disease relapse, nonrelapse mortality, and overall survival. These interim results did not support continuation of the study. We conclude that FA rescue after MTX GVHD prophylaxis does not decrease regimen-related toxicity or affect transplantation outcomes. This study was registered at clinicaltrials.gov as #NCT02506231.

Original languageEnglish
Pages (from-to)3822-3828
Number of pages7
JournalBlood advances
Issue number16
StatePublished - 25 Aug 2020


FundersFunder number
Israel Society of Hematology and Transfusion Medicine


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