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Blood, 15 October 2003, Vol. 102, No. 8, pp. 2728-2730.
Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-02-0663.


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CHEMOKINES
Brief report

Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist

W. Conrad Liles, Hal E. Broxmeyer, Elin Rodger, Brent Wood, Kai Hübel, Scott Cooper, Giao Hangoc, Gary J. Bridger, Geoffrey W. Henson, Gary Calandra, and David C. Dale

From the Department of Medicine, University of Washington, Seattle, WA; the Department of Micro/Immunol and Walther Oncology Center, Indiana University School of Medicine and the Walther Cancer Institute, Indianapolis, IN; and AnorMED Inc, Langley, BC, Canada.

Stromal cell-derived factor 1 (SDF1/CXCL12) and its cognate receptor, CXCR4, play key regulatory roles in CD34+ cell trafficking. We investigated whether AMD3100, a selective CXCR4 antagonist, could mobilize hematopoietic progenitor cells from marrow to peripheral blood in healthy human volunteers. Initially, 10 persons each received a single dose of AMD3100 (80 µg/kg subcutaneously), which induced rapid, generalized leukocytosis associated with an increase in peripheral blood CD34+ cells, representing pluripotent hematopoietic progenitors by in vitro colony-forming unit assays, from 3.8 ± 0.5/µL to 20.7 ± 3.5/µL at 6 hours. Subsequent dose-response studies showed a maximum increase in circulating CD34+ cells from 2.6 ± 0.3/µL to 40.4 ± 3.4/µL at 9 hours after 240 µg/kg AMD3100. Serial administration of AMD3100 (80 µg/kg/d for 3 days) resulted in consistent, reversible increases in peripheral blood CD34+ cells. AMD3100 was well tolerated and caused only mild, transient toxicity. These findings suggest potential clinical application of AMD3100 for CD34+ cell mobilization and collection for hematopoietic stem cell transplantation.


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