Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia givenallogeneic bone marrow transplantation from an HLA-identical sibling: results of a GITMO/EBMT randomized trial

A randomized trial was carried out comparing cyclosporin A (CsA) and shortt erm methotrexate (MTX) versus CsA alone for graft versus host disease (GVHD ) prophylaxis in patients with severe aplastic anemia (SAA) undergoing allo geneic bone marrow transplantation (BMT) from a compatible sibling. Seventy -one patients (median age, 19 years; range, 4-46 years) were randomized to receive either CsA and MTX or CsA alone for the first 3 weeks after BMT, Su bsequently, both groups received CsA orally, with gradual drug reduction un til discontinuation 8 to 12 months after BMT, Patients randomized in both a rms had comparable characteristics and received the same preparative regime n tie, cyclophosphamide 200 mg/kg over 4 days). The median time for neutrop hil engraftment was 17 days (range, 11-31 days) and 12 days (range, 4-45 da ys) for patients in the CsA/MTX group and the CsA alone group, respectively (P = .01), No significant difference was observed in the probability of ei ther grade 2, grade 3, or grade 4 acute GVHD or chronic GVHD developing in the 2 groups. The Kaplan-Meier estimates of 1-year transplantation related mortality rates for patients given either CsA/MTX or CsA alone were 3% and 15%, respectively (P = .07). With a median follow-up of 48 months from BMT, the B-year survival probability is 94% for patients in the CsA/MTX group a nd 78% for those in the CsA alone group (P = .05), These data indicate that the use of CsA with MTX is associated with improved survival in patients w ith SAA who receive transplants from compatible siblings, (C) 2000 by The A merican Society of Hematology.