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Leukocytosis and Mobilization of CD34+ Hematopoietic Progenitor Cells by AMD3100, a CXCR4 Antagonist

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

Supportive cancer therapy, 2004-04, Vol.1 (3), p.165-172 [Periódico revisado por pares]

United States: Elsevier Inc

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  • Título:
    Leukocytosis and Mobilization of CD34+ Hematopoietic Progenitor Cells by AMD3100, a CXCR4 Antagonist
  • Autor: Hübel, Kai ; Liles, W. Conrad ; Broxmeyer, Hal E. ; Rodger, Elin ; Wood, Brent ; Cooper, Scott ; Hangoc, Giao ; MacFarland, Ron ; Bridger, Gary J. ; Henson, Geoffrey W. ; Calandra, Gary ; Dale, David C.
  • Assuntos: Colony-forming units ; Pharmacokenetics ; Safety ; Stem cell mobilization
  • É parte de: Supportive cancer therapy, 2004-04, Vol.1 (3), p.165-172
  • Descrição: Stromal cell–derived factor-1 (SDF-1/CXCL12) plays a key regulatory role in the trafficking of hematopoietic cells. AMD3100 is a specific antagonist of the binding of SDF-1 to its receptor, CXCR4. This phase I study assessed the hematological effects, pharmacokinetics, and safety of administration of AMD3100 to 32 healthy volunteers, including its ability to mobilize CD34+ hematopoietic progenitor cells. A generalized leukocytosis occurred after a single subcutaneous injection of AMD3100 (80 μg/kg) resulting in a maximum white blood cell count of 19.49 ± 1.27 × 103/μL (mean ± SEM) at 6 hours. No changes were observed in erythrocyte or platelet counts. Circulating CD34+ cells increased 5-fold after administration of AMD3100 at 80 μg/kg and 15.5-fold in response to AMD3100 at 240 μg/kg, both at 9 hours after injection. Myeloid progenitor cells—colony forming unit granulocytemacrophage (CFU-GM); CFU-granulocyte, eosinophil, monocyte, megakaryocyte (CFU-GEMM); and burst forming units-erythroid showed similar increases in mobilization to the blood with increasing doses of AMD3100. The mobilized cells were in a slow or noncycling state as determined by in vitro high specific activity of 3H-thymidine. Pharmacokinetic studies showed a near linear increase in peak drug levels with increasing doses and nearly complete elimination of the drug by 24 hours. AMD3100 was well tolerated with only mild and transient toxicities (injection site erythema, headache, paresthesia, nausea, and abdominal distension) observed. These observations suggest that AMD3100 may be a clinically useful agent for hematopoietic progenitor cell mobilization.
  • Editor: United States: Elsevier Inc
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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