ADDITION OF LOW-DOSE FOLINIC ACID TO A METHOTREXATE CYCLOSPORINE-A REGIMEN FOR PREVENTION OF ACUTE GRAFT-VERSUS-HOST DISEASE

A study was performed to determine whether the addition of folinic aci d to a combination of methotrexate (MTX) and cyclosporin A (CsA) after allogeneic bone marrow transplantation (BMT) could improve tolerance to the regimen without inhibiting its ability to prevent graft-versus- host disease (GVHD). Sixty-nine adult BMT patients received CsA plus M TX 15 mg/m(2) on day 1 and 10 mg/m(2) on days +3, +6 and +11. Folinic acid 5 mg was started 24h after each MTX dose and continued 6 hourly u ntil 12h before the next dose of MTX. The median age of the group was 37 years and 13 patients (19%) received bone marrow from mismatched an d/or unrelated donors. No MTX doses were omitted or modified. Grade II -IV acute GVHD occurred in 18 patients (29%) and chronic GVHD in 35 of 56 (64%) patients at risk. There were no cases of grade greater than or equal to III stomatitis. Transplant-related mortality was 7% before 100 days and 20% overall (9% for low risk leukaemia) with a median fo llow-up of 41 months (range 24-88 months). This regimen of folinic aci d rescue may contribute to a well tolerated GVHD prophylaxis protocol with reasonably low BMT-related mortality. Our results suggest that th e ability of MTX to prevent acute GVHD is not abrogated by folinic aci d given in this way.