A combination of granulocyte-colony-stimulating factor (G-CSF) and plerixafor mobilizes more primitive peripheral blood progenitor cells than G-CSF alone: results of a European phase II study.
OBJECTIVE
Previous studies in xenograft models have shown that human peripheral blood progenitor cells (PBPC) mobilized with the CXCR4 antagonist plerixafor (AMD3100) have a higher bone marrow (BM) reconstitution potential than granulocyte-colony-stimulating factor (G-CSF)-mobilized PBPC.


METHODS
PBPC obtained during G-CSF-supported mobilization before and after a supplementary administration of AMD3100 from patients with multiple myeloma and non-Hodgkin's lymphoma (n=15; phase II study) were investigated for co-expression of primitive and lineage-associated markers, their proliferative activity in vitro and repopulation potential after clinical transplantation.


RESULTS
A significant increase in primitive CD34+ CD38(-) cells was observed in intraindividual comparisons of all patients after administration of G-CSF+AMD3100 (peripheral blood: median 8-fold, range 2,4-fold - 39-fold) compared with G-CSF alone. Using a long-term culture-initiating cell assay, this increase was confirmed. After transplantation of G-CSF+AMD3100-mobilized PBPC, the time to leukocyte reconstitution > 1 x 10(3)/microL and platelet reconstitution > 2 x 10(4)/microL was 14 (10-19 days) and 13 days (10-15 days), respectively. A complete and stable hematologic reconstitution (platelets > 1.5 x 10(5)/microL) was observed in 91% of all patients within 35 days.


CONCLUSIONS
An additional application of AMD3100 to a standard G-CSF mobilization regimen leads to a significant increase in primitive PBPC with high repopulation capacity.
Fruehauf
Stefan
S
Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany. prof.stefan.fruehauf@pk-mx.de
Veldwijk
Marlon Romano
MR
Seeger
Timon
T
Schubert
Mario
M
Laufs
Stephanie
S
Topaly
Julian
J
Wuchter
Patrick
P
Dillmann
Falk
F
Eckstein
Volker
V
Wenz
Frederik
F
Goldschmidt
Hartmut
H
Ho
Anthony Dick
AD
Calandra
Gary
G
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D001596:Benzylamines; D018929:Cell Culture Techniques; D000080027:Cyclams; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013997:Time Factors
D018952:Antigens, CD34; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D016179:Granulocyte Colony-Stimulating Factor; D051997:ADP-ribosyl Cyclase 1; C088327:plerixafor