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

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

Research output: Contribution to journalArticle

557 Citations (Scopus)

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
Externally publishedYes

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Hematopoietic Stem Cells
Healthy Volunteers
Blood
Blood Cells
Colony-Forming Units Assay
CXCR4 Receptors
Chemokine CXCL12
Hematopoietic Stem Cell Transplantation
Leukocytosis
Stem cells
Toxicity
JM 3100
Assays
Bone Marrow

ASJC Scopus subject areas

  • Hematology

Cite this

Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. / Liles, W. Conrad; Broxmeyer, Hal; Rodger, Elin; Wood, Brent; Hübel, Kai; Cooper, Scott; Hangoc, Giao; Bridger, Gary J.; Henson, Geoffrey W.; Calandra, Gary; Dale, David C.

In: Blood, Vol. 102, No. 8, 15.10.2003, p. 2728-2730.

Research output: Contribution to journalArticle

Liles, WC, Broxmeyer, H, Rodger, E, Wood, B, Hübel, K, Cooper, S, Hangoc, G, Bridger, GJ, Henson, GW, Calandra, G & Dale, DC 2003, 'Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist', Blood, vol. 102, no. 8, pp. 2728-2730. https://doi.org/10.1182/blood-2003-02-0663
Liles, W. Conrad ; Broxmeyer, Hal ; Rodger, Elin ; Wood, Brent ; Hübel, Kai ; Cooper, Scott ; Hangoc, Giao ; Bridger, Gary J. ; Henson, Geoffrey W. ; Calandra, Gary ; Dale, David C. / Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. In: Blood. 2003 ; Vol. 102, No. 8. pp. 2728-2730.
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