Journal
BLOOD
Volume 102, Issue 8, Pages 2728-2730Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2003-02-0663
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Funding
- NCRR NIH HHS [MO1RR 00037] Funding Source: Medline
- NHLBI NIH HHS [R01 HL 56416] Funding Source: Medline
- NIDDK NIH HHS [R01 DK53674 R01 HL37] Funding Source: Medline
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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 CXCR14 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 mug/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/muL to 20.7 +/- 3.5/muL at 6 hours. Subsequent dose-response studies showed a maximum increase in circulating CD34(+) cells from 2.6 +/- 0.3/muL to 40.4 +/- 3.4/muL at 9 hours after 240 mug/kg AMD3100. Serial administration of AMD3100 (80 mug/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. (C) 2003 by The American Society of Hematology.
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