Role of CXCR4 chemokine receptor blockade using AMD3100 for mobilization of autologous hematopoietic progenitor cells.
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 chemokine SDF-1alpha/CXCL12 binding to its receptor, CXCR4. AMD3100 reversibly inhibits SDF-1alpha/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.
Flomenberg
Neal
N
Thomas Jefferson University, Philadelphia, PA 19701, USA. neal.flomenberg@mail.tju.edu
DiPersio
John
J
Calandra
Gary
G
D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000633:toxicity; D001596:Benzylamines; D001853:Bone Marrow / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D002986:Clinical Trials as Topic; D000080027:Cyclams; D006085:Graft Survival / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000633:toxicity; D006801:Humans; D008223:Lymphoma / Q000378:metabolism / Q000628:therapy; D009101:Multiple Myeloma / Q000378:metabolism / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation; D011485:Protein Binding / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins; D014182:Transplantation, Autologous
D019380:Anti-HIV Agents; D001596:Benzylamines; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor