Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a critical therapeutic strategy for treating conditions such as hematological malignancies, bone marrow failure syndromes, and congenital immunodeficiencies. However, despite various prophylactic measures, acute graft-versus-host disease (aGVHD)-in which donor cells attack the recipient's organs and tissues-remains both a common complication and a leading cause of transplant-related mortality in allo-HSCT.
In a study published in Cell on March 31, a research team led by Prof. ZHAN Cheng from the University of Science and Technology of China (USTC) of the Chinese Academy of Sciences, and Chief Physician ZHU Xiaoyu from the First Affiliated Hospital of USTC has identified how stem cell infusion timing affects the incidence and severity of aGVHD in allo-HSCT, highlighting the role of the recipient's circadian rhythms.
The researchers pioneered a novel approach that takes the recipient's circadian rhythms into account. Using animal models and clinical cohort studies, they explored how stem cell infusion timing affects aGVHD development. The results underscored the importance of infusion timing in allo-HSCT and suggested that infusion early in the day efficiently reduces the incidence and severity of aGVHD.
To confirm the hypothesis, the researchers established major histocompatibility complex (MHC)-mismatched and xenogeneic aGVHD mouse models, infusing stem cells at different times of day. The results showed that the timing of stem cell collection had no impact on aGVHD development, but the recipient's circadian rhythms significantly influenced the onset and severity of aGVHD.
Furthermore, the researchers conducted a single-center peripheral blood stem cell transplantation cohort study as well as a multicenter haploidentical transplantation validation cohort study in China. Both clinical studies corroborated the above findings.
This study provides strong evidence that circadian rhythms play a crucial role in allo-HSCT, underscoring the importance of considering infusion timing when performing transplants. Optimizing stem cell infusion timing may offer a novel strategy to reduce the risk of aGVHD and improve patient outcomes following allo-HSCT.
