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Rapid Mobilization of CD34+ Cells Following Administration of the CXCR4 Antagonist AMD3100 to Patients With Multiple Myeloma and Non-Hodgkin's Lymphoma

Devine, Steven M., Flomenberg, Neal, Vesole, David H., Liesveld, Jane, Weisdorf, Daniel, Badel, Karin, Calandra, Gary, DiPersio, John F.·2004·Journal of Clinical Oncology
DOI 10.1200/jco.2004.07.131
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Abstract

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 I 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 μg/kg (n = 6) or 240 μg/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/μL (mean ± SE) to 15.6 ± 3.9/μL and 16.2 ± 4.3/μL 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 μg/kg group (19.3 ± 6.9/μL and 20.4 ± 7.6/μL, respectively) compared with the 160 μg/kg group (11.3 ± 2.7/μL and 11.3 ± 2.5/μL, 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-stimuating factor in patients with lymphoid malignancies are warranted.

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Cited by

Metadata

Authors
Devine, S. M., Flomenberg, N., Vesole, D. H., Liesveld, J., Weisdorf, D., Badel, K., Calandra, G., & DiPersio, J. F.
Affiliations
From the Washington University School of Medicine, St Louis, MO; Thomas Jefferson University, Philadelphia, PA; Medical College of Wisconsin, Milwaukee, WI; University of Rochester, Rochester, NY; University of Minnesota, Minneapolis, MN; and AnorMed Inc, Langley, British Columbia, Canada.
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2004-03-15
Volume
22
Issue
6
Pages
1095-1102
ISSN
  • 0732-183X
  • 1527-7755
DOI
10.1200/jco.2004.07.131
Cited by
368
References
0
Language
en

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