Effect of methotrexate dose in graft-versus-host disease prophylaxis after single-unit cord blood transplantation in adult acute myeloid leukemia.

To investigate the association between methotrexate (MTX) dosage and engraftment, graft-versus-host disease (GVHD) incidence, and survival in umbilical cord blood transplantation (UCBT), we compared transplant outcomes after UCBT with various GVHD prophylaxis regimens, using registry data with additional data collection. Patients transplanted for acute myeloid leukemia with a calcineurin inhibitor (CNI) and either MTX or mycophenolate mofetil (MMF) combination were selected. In total, 888 single-unit UCBTs (MTX15-10-10, 415; MTX10-7-7, 294; MTX5-5-5, 71; MMF, 108) were included. In multivariate analyses with MTX15-10-10 as the reference, the likelihood of neutrophil and platelet engraftment was significantly worse in the MTX10-7-7 group, and similarly better in MMF group compared with MTX15-10-10. All variables including CyA vs Tac and 4-group GVHD prophylaxis became significant for the risk of grade II-IV acute GVHD in the final multivariate model. We observed significant additional effects of combined MTX dose in the Tac group, which were larger with lower MTX dose and MMF. No significant difference was observed in survival risk among GVHD prophylaxis groups. Despite the potential background differences in the combined CNI and conditioning regimen, we conclude that the recommended GVHD prophylaxis is a combination of CyA plus MTX15-10-10 or Tac plus MMF.