Decreased incidence of graft-versus-host disease and improved survival with methotrexate combined with cyclosporin compared with monotherapy in recipients of bone marrow from donors other than HLA identical siblings

Abstract

Recipients receiving marrow from donors other than HLA identical siblings (alternative donors) treated by monotherapy with either methotrexate (MTX, n = 5) or cyclosporin A (CSA, n = 10) were compared with 28 recipients of alternative donor marrow receiving MTX + CSA. The former group had a cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) of 73% compared with 34% in the latter group (p = 0.009). The incidence of chronic GVHD was 75% and 41% in the two groups respectively, a difference that was not statistically significant. Death caused by GVHD was 47% in recipients of alternative bone marrow treated with monotherapy vs 12% in those treated with MTX + CSA (p = 0.008). The actuarial 4-year patient survival was 7% and 46% in the two groups, respectively (p = 0.04). Compared with HLA identical siblings the recipients of alternative marrow treated with monotherapy had an increased risk of grade II-IV acute GVHD (p less than 0.0001), an increased death rate by GVHD (p = 0.0001) and a decreased survival (p less than 0.0001). When MTX was combined with CSA the recipients of alternative marrow had an increased risk of grade II-IV acute GVHD (p = 0.005), but death by GVHD (12 vs 6%) and 4-year patient survival (46 vs 45%) did not differ.