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

WC Liles, HE Broxmeyer, E Rodger, B Wood, K Hübel… - Blood, 2003 - ashpublications.org
WC Liles, HE Broxmeyer, E Rodger, B Wood, K Hübel, S Cooper, G Hangoc, GJ Bridger…
Blood, 2003ashpublications.org
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 …
Abstract
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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