Folinic acid after MTX as prophylaxis for GVHD in pediatric bone marrow transplantation

Abstract

The effect of folinic acid (FA) on toxicity secondary to the use of methotrexate (MTX) for the prevention of graft-versus-host disease (GVHD) has not been determined. We retrospectively analyzed data from 111 patients who received allogeneic bone marrow transplantation (allo-BMT) in our institution. Fifty patients did not receive FA (non-FA), 37 received FA four times (low dose, LD-FA), and 24 received FA 25 times (high dose, HD-FA) in BMT. No significant differences were observed in the severity of stomatitis after allo-BMT among the three groups while the median of peak value of ALT in HD-FA was significantly lower (P = 0.031). The median time to neutrophil engraftment after allo-BMT in the HD-FA group was significantly shorter than that in the non-FA group (P = 0.034). No significant difference in the median time to neutrophil engraftment was observed between the LD-FA and non-FA groups (P = 0.44). Stepwise multiple regression analysis revealed that the determinants of the shorter duration of neutropenia were transfused total nucleated cell dose (P = 0.001) and the administration of HD-FA (P = 0.036). There was no significant difference in 3-year overall survival among the three groups. Frequent administration of FA may reduce the time to neutrophil engraftment after hematopoietic stem cell transplantation.

Methotrexate-induced Oral Mucositis

“…1) MTX is also widely used as a therapeutic agent for chronic inflammatory disorders such as rheumatoid arthritis (RA), 2) psoriasis, 3) systemic lupus erythematosus, 4) granulomatosis with polyangiitis (Wegener's), 5) Crohn disease 6) and in the prevention of graft-versus-host disease. 7) MTX is a folic acid (FA) antagonist that interferes reversibly with the action of several key enzymes including dihydrofolate-reductase, thymidilate synthetase and amino-imidazolecarboxamide ribosyl-5-phosphate (AICAR) transformylase in the folate pathway. 8) These enzymes are requisite for the synthesis of purines and pyrimidines.…”