Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction.
Allografts from HLA-matched sibling donors were mobilized and collected without granulocyte colony-stimulating factor (G-CSF) using AMD3100, a direct antagonist of CXCR4/stromal-derived factor 1 (SDF-1/CXCL12). Donors (N = 25) were treated with AMD3100 at a dose of 240 mug/kg by subcutaneous injection, and leukapheresis was then initiated just 4 hours later. Two-thirds of the donors collected an allograft with a CD34(+) cell dose sufficient for transplantation after just one dose of AMD3100. No donor experienced more than grade 1 toxicity. After a myeloablative regimen, 20 patients with hematologic malignancies received allografts collected after AMD3100 alone. All patients engrafted neutrophils (median day 10) and platelets (median day 12) promptly. Acute graft-versus-host disease (GVHD) grades 2 through 4 occurred in 35% of patients. One patient died due to complications related to acute GVHD. No unexpected adverse events were observed in any of the recipients. All 14 patients surviving in remission have robust trilineage hematopoiesis and are transfusion-free with a median follow-up of 277 days (range, 139-964 days). Direct antagonism of CXCR4 by AMD3100 may provide a more rapid and possibly less toxic and cumbersome alternative to traditional G-CSF-based mobilization in normal donors. This trial was registered as no. NCT00241358 at www.ClinicalTrials.gov.
Devine
Steven M
SM
The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. steven.devine@osumc.edu
Vij
Ravi
R
Rettig
Michael
M
Todt
Laura
L
McGlauchlen
Kiley
K
Fisher
Nicholas
N
Devine
Hollie
H
Link
Daniel C
DC
Calandra
Gary
G
Bridger
Gary
G
Westervelt
Peter
P
Dipersio
John F
JF
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D001596:Benzylamines; D054377:Chemokine CXCL12 / Q000378:metabolism; D000080027:Cyclams; D005260:Female; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000628:therapy; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D011485:Protein Binding / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016019:Survival Analysis; D014019:Tissue Donors; D014184:Transplantation, Homologous
D018952:Antigens, CD34; D001596:Benzylamines; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor