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. STUDY DESIGN AND METHODS: Five normal subjects were randomly assigned to each of the following single-dose regimens in 5 consecutive weeks: 1) G-CSF, 300 mu g given subcutaneously; 2) G-CSF, 600 mu g subcutaneously; 3) dexamethasone, 8 mg given orally; 4) G-CSF 300 mu g subcutaneously, plus dexamethasone, 8 mg orally; and 5) G-CSF, 600 mu g 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 mu g) and dexamethasone (8 mg): the ANC increased from a mean baseline value of 3,594 per mu L to 43,017 per mu L at 12 hours. All of the drug regimens were well tolerated. CONCLUSION: 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.