A novel CXCR4 antagonist for hematopoietic stem cell mobilization

Abstract

Background: Hematopoietic stem cell (HSC) transplantation is a treatment option for hematological malignancies. Current mobilization regimes frequently result in inadequate numbers of HSC for transplant therefore alternative methods of mobilization are required.

Objective: The chemokine receptor CXCR4 and ligand SDF-1 are integrally involved in HSC homing and mobilization. Disruption of the SDF-1/CXCR4 axis by the CXCR4 anatagonist, plerixafor, is shown to improve HSC mobilization.

Methods: The molecular and in vivo pharmacology of plerixafor and subsequent clinical development is reviewed.

Results/conclusion: Preclinical studies demonstrate that plerixafor is a selective antagonist of CXCR4 and can rapidly mobilize HSC. Clinical trials demonstrated improved HSC mobilization when plerixafor was included in the mobilization regimen. These data suggest the potential for a significant role for plerixafor in hematological disease.