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, David C. Dale

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571 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2728-2730
Number of pages3
JournalBlood
Volume102
Issue number8
DOIs
StatePublished - Oct 15 2003

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Liles, W. C., Broxmeyer, H. E., Rodger, E., Wood, B., Hübel, K., Cooper, S., Hangoc, G., Bridger, G. J., Henson, G. W., Calandra, G., & Dale, D. C. (2003). Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood, 102(8), 2728-2730. https://doi.org/10.1182/blood-2003-02-0663