Prospective cohort study of the circadian rhythm pattern in allogeneic sibling donors undergoing standard granulocyte colony-stimulating factor mobilization

Introduction: Prior in vivo murine studies suggest circadian oscillations for hematopoietic stem cell release, which are maintained following administration of granulocyte colony-stimulating factor (G-CSF) or plerixafor. Furthermore, retrospective data analysis of healthy donors who underwent G-CSF-induced mobilization demonstrated significantly increased CD34(+) cell yields when collected in the afternoon compared with the morning. Methods: A prospective study was conducted to directly examine the number of peripheral blood CD34(+) and CD34(+)CD38(-) progenitor/stem cells at baseline and then every 6 hours for 24 hours on days 4 to 5 of G-CSF (10 mu g/kg/day in the morning) mobilization in 11 allogeneic donors. Data were analyzed using mixed-model analysis of repeated measures. Results: Whereas we observed a significant increase in CD34(+) cell counts toward the evening, counts were then sustained on the morning of day 5. The correlation between CD34(+)CD38(-)cell counts and the less defined CD34(+) populations was weak. Conclusions: Our results suggest that the pharmacodynamic activity and timing of G-CSF may alter endogenous progenitor rhythms. Donor age, medical history, and medications may also impact circadian rhythm. Further studies should examine the circadian rhythm at the peak of G-CSF mobilization and and should consider potential confounders such as the time of G-CSF administration and the age of the subjects.