Rapid mobilization of CD34+cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma

Purpose Interactions between the chemokine receptor CXCR4 and its ligand stromal derived factor-1 regulate hematopoietic stem-cell trafficking, AMD3100 is a CXCR4 antagonist that induces rapid mobilization of CD34+ cells in healthy volunteers. We performed a phase 1 study assessing the safety and clinical effects of AMD3100 in patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Patients and Methods Thirteen patients (MM, n = 7; NHL, n = 6) received AMD3100 at a dose of either 160 mug/kg (n = 6) or 240 mug/kg (n = 7). WBC and peripheral blood (PB) CD34+ cell counts were analyzed at 4 and 6 hours following injection. Results AMD3100 caused a rapid and statistically significant increase in the total WBC and PB CD34+ counts at both 4 and 6 hours following a single injection. The absolute CD34+ cell count increased from a baseline of 2.6 +/- 0.7/muL (mean +/- SE) to 15.6 +/- 3.9/muL and 16.2 +/- 4.3/muL at 4 hours (P = .002) and 6 hours after injection (P = .003), respectively. The absolute CD34+ cell counts observed at 4 and 6 hours following AMD3100 were higher in the 240 mug/kg group (19.3 +/- 6.9/muL and 20.4 +/- 7.6/muL, respectively) compared with the 160 mug/kg group (11.3 +/- 2.7/muL and 11.3 +/- 2.5/muL, respectively). The drug was well tolerated and only grade 1 toxicities were encountered. Conclusion AMD3100 appears to be a safe and effective agent for the rapid mobilization of CD34+ cells in patients who have received prior chemotherapy. Further studies in combination with granulocyte colony-stimulating factor in patients with lymphoid malignancies are warranted.