Role of CXCR4 Chemokine Receptor Blockade Using AMD3100 for Mobilization of Autologous Hematopoietic Progenitor Cells

Vol. 114, No. 4, 2005

Free Abstract Article (Fulltext) Article (PDF 136 KB)

Paper

Role of CXCR4 Chemokine Receptor Blockade Using AMD3100 for Mobilization of Autologous Hematopoietic Progenitor Cells
Neal Flomenberg^a, John DiPersio^b, Gary Calandra^c

^aThomas Jefferson University,
^bDivision of Medical Oncology,Thomas Jefferson University Hospital, Philadelphia, Pa.,
^cWashington University, St. Louis, Mo., USA, and AnorMED, Inc., Langley, Canada

Address of Corresponding Author

Acta Haematol 2005;114:198-205 (DOI: 10.1159/000088410)

Key Words

CD34+ cell mobilization
Autotransplantation
CXCR4
SDF-1/CXCL12
Hematopoietic progenitor cell mobilization

Abstract

G-CSF mobilization of hematopoietic progenitor cells (HPCs) is mediated through enzyme release from maturing myeloid cells, leading to digestion of adhesion molecules, trophic chemokines and their receptors, and the extracellular matrix. HPCs traffic to and are retained in the marrow through the trophic effects of the chemo kine SDF-1 alpha /CXCL12 binding to its receptor, CXCR4. AMD3100 reversibly inhibits SDF-1 alpha /CXCR4 binding, and AMD3100 administration mobilizes CD34+ cells into the circulation. AMD3100 has been tested in several clinical trials which demonstrate that it improves the number of CD34+ cells mobilized including patients failing to mobilize with G-CSF alone. Engraftment of AMD3100-mobilized cells is prompt and durable. Toxicities are mild and infrequent. Lymphoma and myeloma cells do not appear to be mobilized. AMD3100 appears to be a promising agent for HPC mobilization.

Author Contacts

Neal Flomenberg
Thomas Jefferson University, Division of Medical Oncology
801 Sheridan Building, 125 S. 9th Street
Philadelphia, PA 19107 (USA)
Tel. +1 215 955 4367, Fax +1 215 955 9641, E-Mail neal.flomenberg@mail.tju.edu

Article Information

Data from the clinical trials presented in this article are excerpted from their last abstract presentations and thus reflect summaries of materials already in the public domain. None of these studies have yet been published in final form.

Number of Print Pages : 8
Number of Figures : 0, Number of Tables : 1, Number of References : 51

Medline Abstract (ID 16269859)

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