A comparative trial of granulocyte-colony-stimulating factor and dexamethasone, separately and in combination, for the mobilization of neutrophils in the peripheral blood of normal volunteers.
BACKGROUND
The clinical utility of polymorphonuclear neutrophil (PMN) transfusion therapy has been compromised, in part, by the inability to obtain sufficient quantities of functional neutrophils from donors. To define the optimal conditions for mobilization of PMNs in granulocyte donors, the effects of granulocyte-colony-stimulating factor (G-CSF) and dexamethasone, separately and in combination, on PMN counts in normal volunteers were compared.


METHODS
Five normal subjects were randomly assigned to each of the following single-dose regimens in 5 consecutive weeks: 1) G-CSF, 300 micrograms given subcutaneously; 2) G-CSF, 600 micrograms subcutaneously: 3) dexamethasone, 8 mg given orally; 4) G-CSF, 300 micrograms subcutaneously, plus dexamethasone, 8 mg orally; and 5) G-CSF, 600 micrograms subcutaneously, plus dexamethasone 8 mg orally. Venous blood was collected at 0, 6, 12, and 24 hours after drug administration for the determination of absolute neutrophil counts (ANCs).


RESULTS
Maximal ANC was achieved at 12 hours after each regimen, except dexamethasone alone (maximum, 24 hours). Dexamethasone significantly increased the maximal ANC induced by either dose of G-CSF alone (p < 0.05). The greatest mobilization of PMNs occurred after the administration of G-CSF (600 micrograms) and dexamethasone (8 mg); the ANC increased from a mean baseline value of 3,594 per microL to 43,017 per microL at 12 hours. All of the drug regimens were well tolerated.


CONCLUSIONS
Dexamethasone significantly increases the level of neutrophilia induced in normal subjects by G-CSF. The combination of dexamethasone and G-CSF (at the dosages used in this study) is a convenient, well-tolerated regimen for the mobilization of PMNs in the peripheral blood of granulocyte donors. Moreover, the optimal quantitative yield of PMNs is likely to be achieved by leukapheresis 12 hours after drug administration.
Liles
W C
WC
Department of Medicine, University of Washington, USA.
Huang
J E
JE
Llewellyn
C
C
SenGupta
D
D
Price
T H
TH
Dale
D C
DC
D000293:Adolescent; D000328:Adult; D003907:Dexamethasone / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D015994:Incidence; D007958:Leukocyte Count / Q000187:drug effects; D007964:Leukocytosis / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects*
D016179:Granulocyte Colony-Stimulating Factor; D003907:Dexamethasone