Influence of time-of-day of graft infusion on allogeneic hematopoietic stem cell transplantation outcomes: a validation cohort study

The biological clock plays a central role in hematopoiesis and immune regulation, making circadian rhythms an increasingly important factor in immunotherapies and cellular therapies such as allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous work by Hou <i>et al</i> suggested that afternoon graft infusions were associated with a higher risk of acute graft-versus-host disease and worse survival, highlighting a potential role for infusion timing in shaping transplant outcomes.To further investigate this, we performed a retrospective analysis of 368 patients who underwent allo-HSCT at Geneva University Hospitals between 2015 and 2024. Observing that infusion timing patterns at our center differed from those reported by Hou <i>et al</i>, we applied a data-driven approach using receiver operating characteristic analysis, which identified 11:17 as the optimal cut-off for overall survival.Stratification using this threshold revealed that patients receiving grafts before 11:00 had significantly improved 2-year overall survival and lower non-relapse mortality compared with those infused later in the day, with no differences in relapse or engraftment rates.These findings suggest that infusion timing may be an important, under-recognized factor influencing allo-HSCT outcomes. Prospective clinical trials are needed to confirm these observations and explore their applicability across different clinical contexts.