Augmented mobilization and collection of CD34+ hematopoietic cells from normal human volunteers stimulated with granulocyte-colony-stimulating factor by single-dose administration of AMD3100, a CXCR4 antagonist.
BACKGROUND
AMD3100, a selective antagonist of CXCR4, rapidly mobilizes CD34+ hematopoietic progenitor cells (HPCs) from marrow to peripheral blood with minimal side effects.


METHODS
To further investigate potential clinical utility of AMD3100 for CD34+ cell mobilization and collection, a Phase I study in normal volunteers was performed examining single-dose administration of AMD3100 alone and in combination with a standard 5-day granulocyte-colony-stimulating factor (G-CSF) regimen.


RESULTS
AMD3100 (160 microg/kg x 1 on Day 5) significantly increased both G-CSF-stimulated (10 microg/kg/day) mobilization of CD34+ cells (3.8-fold) and leukapheresis yield of CD34+ cells. Moreover, collection of CD34+ cells was comparable between individuals mobilized by a single-dose regimen of AMD3100 (240 microg/kg) and individuals mobilized with a 5-day regimen of G-CSF. AMD3100-mobilized leukapheresis products contained significantly greater numbers of T and B cells compared to G-CSF-stimulated leukapheresis products.


CONCLUSIONS
These findings indicate that AMD3100 can be used alone or as an adjunct to G-CSF to mobilize cells for HPC transplantation.
Liles
W Conrad
WC
Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
Rodger
Elin
E
Broxmeyer
Hal E
HE
Dehner
Christine
C
Badel
Karin
K
Calandra
Gary
G
Christensen
Jeff
J
Wood
Brent
B
Price
Thomas H
TH
Dale
David C
DC
D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018952:Antigens, CD34 / Q000378:metabolism; D001596:Benzylamines; D015331:Cohort Studies; D000080027:Cyclams; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000008:administration & dosage*; D006805:Human Experimentation; D006801:Humans
D019380:Anti-HIV Agents; D018952:Antigens, CD34; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor