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Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-02-0663.

Submitted March 3, 2003
Accepted June 26, 2003
Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist
W C Liles, Hal E Broxmeyer, Elin Rodger, Brent Wood, Kai Hubel, Scott Cooper, Giao Hangoc, Gary J Bridger, Geoffrey W Henson, Gary Calandra, and David C Dale*
Department of Medicine, University of Washington, Seattle, WA, USA
Department of Micro/Immunol & Walther Oncol. Center, Indiana University School of Medicine, Indianapolis, IN, USA
AnorMED Inc., Langley, BC, Canada
* Corresponding author; email: dcdale{at}u.washington.edu.
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 individuals 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 6h. 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 9h after 240 mg/kg of AMD3100. Serial administration of AMD3100 (80 µg/kg/d x 3d) caused consistent, reversible increases in peripheral blood CD34+ cells. AMD3100 administration was well-tolerated with 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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