Acute graft-versus-host disease is the foremost cause of late nonrelapse mortality.

Despite low nonrelapse mortality (NRM) at day 100 after allogeneic hematopoietic cell transplantation (HCT), NRM at 1 year remains substantial. In this study, we retrospectively analyzed 199 patients who were treated on a phase II clinical trial assessing safety and efficacy of myeloablative fractionated busulfan and fludarabine conditioning regimen for hematologic malignancies. The goal of the study was to identify factors associated with NRM occurring between days 101 and 365 post-HCT and generate a hypothesis for future studies to reduce the risk of NRM at 1 year. We found that a vast majority (83%) of patients who experienced NRM between days 101 and 365 had prior grade II-IV acute graft-versus-host disease (GVHD), which was the leading cause of death either by itself (33.3%) or complicated by infections (37.5%). In multivariate analysis, grade II-IV acute GVHD (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.3-6.6, p = 0.01) was the only significant predictor of NRM between days 101 and 365. Measures to reduce the risk of acute GVHD could lower the risk of NRM at 1 year and improve overall survival.