Cyclosporine alone vs cyclosporine plus methotrexate for post-transplant immunosuppression after HLA-identical sibling bone marrow transplantation: A randomized prospective study

The role of methotrexate (MTX), given with cyclosporine (CS), after HLA-identical sibling bone marrow transplantation needs to be defined. In all, 80 patients with hematologic malignancies were enrolled in a prospective randomized trial. All were given BuCy conditioning. The 40 patients in the CS arm received CS 3mg/kg/day intravenously, with subsequent oral dosing. Patients in the CS + MTX arm received, in addition to CS, MTX intravenously, 15 mg/m² on day 1, and 10 mg/m² on days 3, 6, and 11. Transplantation-related mortality was low in both groups of patients (13 vs 11 % for CS vs CS + MTX groups, P=0.94). The CS group had a significantly higher frequency of chronic graft-versus-host disease (56 vs 32%, P = 0.05). After a median follow-up of 22.1 months (5.1-47.8 months), three of 30 vs 10 of 28 patients with acute leukemia/myelodysplastic syndrome (MDS) in CS group vs CS+MTX group relapsed (P=0.01) yielding better overall survival for patients with acute leukemia/MDS treated with CS (P = 0.02). After HLA-identical sibling bone marrow transplantation, immunosuppression with CS, with or without MTX, resulted in similarly low transplantation-related mortality. In acute leukemia/MDS, decreased relapse with patient survival prolongation was observed in the CS group.