GVHD prophylaxis after cord blood transplantation in patients with high-risk AML: a nationwide Japanese cohort study

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 (P < .001). However, CSP/TAC + MMF showed significantly higher incidences of grades 2 to 4 acute GVHD (P < .001) and chronic GVHD (P < .001). Two-year transplant-related mortality and relapse rates were 26 to 38% and 41 to 46%, respectively. Overall survival and disease-free survival at 2 years were higher with MTX than with MMF (P < .001 and P = .003, respectively), indicating a modest survival advantage for MTX. Multivariable analysis identified older age (≥55 years), male sex, Karnofsky performance status <80, higher hematopoietic cell transplantation-specific comorbidity index, and no remission at transplantation as adverse prognostic factors. Notably, MMF use was associated with an increased risk of human herpesvirus 6 encephalitis. Both CSP/TAC + MMF and CSP/TAC + MTX regimens support successful CBT in high-risk AML. Although MMF accelerates engraftment, this benefit is offset by greater GVHD and viral complications. These real-world, nationwide data highlight the need to individualize GVHD prophylaxis based on patient and transplant characteristics and provide essential benchmarks for future multicenter prospective studies.