title: Addition of low-dose folinic acid to a methotrexate/cyclosporin A regimen for prevention of acute graft-versus-host disease.
abstract: A study was performed to determine whether the addition of folinic acid 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 MTX 15 mg/m2 on day 1 and 10 mg/m2 on days +3, +6 and +11. Folinic acid 5 mg was started 24 h after each MTX dose and continued 6 hourly until 12 h before the next dose of MTX. The median age of the group was 37 years and 13 patients (19%) received bone marrow from mismatched and/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 > or = III stomatitis. Transplant-related mortality was 7% before 100 days and 20% overall (9% for low risk leukaemia) with a median follow-up of 41 months (range 24-88 months). This regimen of folinic acid rescue may contribute to a well tolerated GVHD prophylaxis protocol with reasonably low BMT-related mortality. Our results suggest that the ability of MTX to prevent acute GVHD is not abrogated by folinic acid given in this way.
authors.affiliation: Department of Medicine, Foothills Hospital, Calgary, Canada.
authors.forename: J A
authors.initials: JA
authors.lastname: Russell
authors.forename: R C
authors.initials: RC
authors.lastname: Woodman
authors.forename: M C
authors.initials: MC
authors.lastname: Poon
authors.forename: A R
authors.initials: AR
authors.lastname: Jones
authors.forename: B A
authors.initials: BA
authors.lastname: Ruether
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use*; D007938:Leukemia / Q000188:drug therapy / Q000628:therapy; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D014184:Transplantation, Homologous
chemical_list: D016572:Cyclosporine; D002955:Leucovorin; D008727:Methotrexate