Cord blood transplantation (CBT) is a curative option for patients with high-risk acute myeloid leukemia (AML), including therapy-related AML (t-AML). However, the optimal prophylaxis for graft-versus-host disease (GVHD) remains unclear. We conducted a nationwide, retrospective cohort study including 3222 adults with high-risk AML (t-AML and non-t-AML) who underwent their first CBT in Japan between 2010 and 2023. GVHD prophylaxis consisted of cyclosporine or tacrolimus combined with mycophenolate mofetil (CSP/TAC+MMF) or methotrexate (CSP/TAC+MTX). MMF regimens were associated with faster neutrophil engraftment than MTX regimens (P0.001). However, CSP/TAC+MMF was associated with a significantly higher incidence of grades II-IV acute GVHD (4 P0.001) and chronic GVHD (P0.001) than CSP/TAC+MTX. Two-year transplant-related mortality and relapse rates were 26%-38% and 41%-46%, respectively. At 2 years post-transplant, overall survival rates were higher with MTX than with MMF (P0.001). Disease-free survival rates were also higher with MTX than with MMF (P=0.003). Therefore, a modest survival advantage was observed for MTX. Multivariable analysis identified older age (≥55 years), male sex, Karnofsky performance status 80, a higher hematopoietic cell transplantation-comorbidity index, and non-remission at transplantation as adverse prognostic factors. Importantly, MMF was associated with an increased risk of human herpesvirus 6 encephalitis. CSP/TAC+MMF and CSP/TAC+MTX support successful CBT for high-risk AML. While MMF accelerates engraftment, this is offset by greater GVHD and viral complications. These real-world, nationwide data highlight the need to individualize GVHD prophylaxis on the basis of patient and transplant characteristics and provide essential benchmarks for future prospective, multicenter studies.
Yamasaki et al. (Thu,) studied this question.