The CXCR4 Antagonist AMD3100 Mobilizes a More Primitive Subset of CD34+ Cells Than G-CSF.

The CXCR4-antagonist AMD3100 mobilizes peripheral blood progenitor cells (PBPC) in 8–10 hours while a standard mobilization regimen with granulocyte colony-stimulating factor (G-CSF) takes 4 days before significant numbers of PBPC can be detected. Recently it was shown that AMD3100-mobilized PBPC have a higher reconstitution potential in the NOD/SCID mouse model than G-CSF mobilized PBPC. Clinically they also mediate rapid and sustained engraftment after transplantation. Prospective comparative studies are yet lacking. It can be expected that the functional differences are also reflected on the phenotypic level. We used 6-color and 3-color flow cytometry to study the co-expression of primitive and lineage-associated markers on mobilized PBPC of patients with multiple myeloma and non-Hodgkin’s lymphoma (n=5). Mobilization treatment consisted of 5 days G-CSF (10 μg/kg, s.c. AM) and a single dose of AMD3100 (240 μg/kg, s.c.) in the evening of day 4. CD34+ cells of day 4, before AMD3100-dosing (G-CSF group) and on day 5, 10-hours after AMD3100 (AMD3100+G-CSF group) were compared. Primitive CD34+/CD38- cells which solely mediate hematopoietic reconstitution in the NOD/SCID mouse model were increased after addition of AMD3100 in all patients by a median of 2,58 fold (range 1,19–6,66) while the myeloid lineage committed CD34+/CD117+ and the actively proliferating CD34+/CD71+ cell subsets were significantly downregulated (p<0,05 each). The myeloid CD34+/CD33+ cell population showed a similar trend (median 0,60-fold change, range 0,24–1,08). Adhesion molecules were significantly regulated (CD49b) or showed such a trend (CD49d). Quantification of aldehyde dehydrogenase (AlDH) positive cells in A+G vs. G-CSF-mobilized samples did not show significant differences between these groups. We conclude that AMD3100 mobilizes a more primitive subset of CD34+ progenitor cells than G-CSF alone. Whether this translates into lower CD34+ threshold values for transplantation to achieve a similarly rapid and sustained engraftment after transplantation or into a shorter reconstitution period if similar amounts of CD34+ cells are used as after standard G-CSF-mobilization needs further study.