Diabetes Limits Stem Cell Mobilization Following G-CSF but Not Plerixafor

Abstract

Previous studies suggest that diabetes impairs hematopoietic stem cell (HSC) mobilization in response to granulocyte colony-stimulating factor (G-CSF). In this study, we tested whether the CXCR4 antagonist plerixafor, differently from G-CSF, is effective in mobilizing HSCs in patients with diabetes. In a prospective study, individuals with and without diabetes (n = 10/group) were administered plerixafor to compare CD34(+) HSC mobilization; plerixafor was equally able to mobilize CD34(+) HSCs in the two groups, whereas in historical data, G-CSF was less effective in patients with diabetes. In a retrospective autologous transplantation study conducted on 706 patients, diabetes was associated with poorer mobilization in patients who received G-CSF with/without chemotherapy, whereas it was not in patients who received G-CSF plus plerixafor. Similarly in an allogeneic transplantation study (n = 335), diabetes was associated with poorer mobilization in patients who received G-CSF. Patients with diabetes who received G-CSF without plerixafor had a lower probability of reaching >50/μL CD34(+) HSCs, independent from confounding variables. In conclusion, diabetes negatively impacted HSC mobilization after G-CSF with or without chemotherapy but had no effect on mobilization induced by G-CSF with plerixafor. This finding has major implications for the care of patients with diabetes undergoing stem cell mobilization and transplantation and for the vascular regenerative potential of bone marrow stem cells.

Trial registration: ClinicalTrials.gov NCT02056210.

Figure 1

Summary results of the prospective plerixafor trial and comparison with historical G-CSF data. For subjects with and without diabetes, changes in the levels of CD34⁺ HSCs, as well as HSC colonies after plerixafor are reported as box and whisker plot, individual patient lines, and fold changes. *P < 0.05 vs. baseline or vs. nondiabetic (for fold-change comparison). CFU-GM, colony-forming units–granulocyte macrophage.

Figure 2

Achieved CD34⁺ HSC count in the retrospective studies. Patients undergoing HSC mobilization and collection for autologous transplantation (auto) were divided into those who received G-CSF with or without chemotherapy and those who received G-CSF with plerixafor. Subjects undergoing HSC mobilization and collection for allogeneic donation (allo) only received G-CSF. Then patients were divided based on a history of diabetes (DM) or not (CTRL). *P < 0.05 DM vs. CTRL.