TY - JOUR
T1 - Efficacy of folinic acid rescue following MTX GVHD prophylaxis
T2 - Results of a double-blind, randomized, controlled study
AU - Yeshurun, Moshe
AU - Rozovski, Uri
AU - Pasvolsky, Oren
AU - Wolach, Ofir
AU - Ram, Ron
AU - Amit, Odelia
AU - Zuckerman, Tsila
AU - Pek, Anat
AU - Rubinstein, Maly
AU - Sela-Navon, Michal
AU - Raanani, Pia
AU - Shargian-Alon, Liat
N1 - Publisher Copyright:
© 2020 by The American Society of Hematology.
PY - 2020/8/25
Y1 - 2020/8/25
N2 - 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.
AB - 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.
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U2 - 10.1182/bloodadvances.2020002039
DO - 10.1182/bloodadvances.2020002039
M3 - Article
C2 - 32790844
AN - SCOPUS:85090341409
SN - 2473-9529
VL - 4
SP - 3822
EP - 3828
JO - Blood Advances
JF - Blood Advances
IS - 16
ER -