EARLY morning cord blood transplantation significantly reduces acute graft-versus-host disease severity and improves survival, highlighting infusion timing as a modifiable factor in allogeneic hematopoietic stem cell transplantation outcomes.
Cord Blood Transplantation Timing And GVHD
Allogeneic hematopoietic stem cell transplantation is a cornerstone therapy for malignant and non-malignant haematological diseases, yet acute graft-versus-host disease remains a major complication. Previous research using fresh grafts has shown that early day stem cell infusions lower both the incidence and severity of acute graft-versus-host disease. Whether this timing effect extends to cryopreserved grafts has remained uncertain. The current study addresses this gap by examining early morning cord blood transplantation using unrelated cord blood grafts. The findings demonstrate that early morning infusion of unrelated cord blood significantly reduced the severity of acute graft-versus-host disease and was associated with improved survival when compared with later infusion times.
Circadian Biology and Immune Response
The investigators explored biological mechanisms underlying the observed clinical differences. Data showed that circadian variation in circulating cytokines correlated with acute graft-versus-host disease severity following cord blood transplantation. Among these factors, soluble CD26 emerged as a key mediator. Levels of soluble CD26 varied according to the time of infusion and were closely associated with disease severity. These findings suggest that immune activation following allogeneic hematopoietic stem cell transplantation is influenced by circadian rhythms, with early morning cord blood transplantation aligning more favourably with host immune biology.
Targeting Soluble CD26 For Late Infusions
To further interrogate the role of soluble CD26, the study evaluated pharmacological inhibition of its enzymatic activity. Administration of Sitagliptin significantly mitigated acute graft-versus-host disease and improved survival in late infused female mice. This intervention appeared to offset the disadvantage associated with delayed cord blood transplantation. Together, the results indicate that early morning cord blood transplantation may represent a simple prophylactic strategy, while targeting soluble CD26 could offer a therapeutic option when early infusion is not feasible. These insights reinforce the importance of infusion timing and circadian biology in optimising outcomes following allogeneic hematopoietic stem cell transplantation.
Reference
Wu Y et al. Circadian fluctuation of soluble CD26 dictates the impact of the timing of cord blood transplantation on acute graft-versus-host disease. Nature Communications. 2026; https://doi.org/10.1038/s41467-026-68958-4.
