Combined administration of G-CSF and dexamethasone for the mobilization ofgranulocytes in normal donors: optimization of dosing

BACKGROUND: The clinical utility of neutrophil (polymorphonuclear leukocyte , PMN) transfusion therapy has been compromised, in part, by the inability to obtain sufficient quantities of functional neutrophils from donors. Mobi lization of PMNs in the peripheral blood of normal volunteers has been show n to be superior when G-CSF is administered in conjunction with dexamethaso ne to that when either agent is administered alone. The current study was c onducted to determine the optimal dosages of G-CSF and dexamethasone to be administered to donors in a granulocyte transfusion program. STUDY DESIGN AND METHODS: Five normal subjects were randomly assigned to ea ch of the following single-dose regimens over five consecutive weeks: 1) su bcutaneous (SC) G-CSF at 600 mu g and oral (PO) dexamethasone at 8 mg; 2) S C G-CSF at 450 mu g and PO dexamethasone at 8 mg; 3) SG G-CSF at 450 mu g a nd PO dexamethasone at 12 mg; 4) SC G-CSF at 450 mu g; and 5) PO dexamethas one at 12 mg. Venous blood was collected at 0, 6, 12, and 24 hours after dr ug administration for determination of absolute neutrophil count (ANC). Sid e effects of drug administration were recorded by using a standardized symp tom questionnaire. RESULTS: Maximal ANC was achieved at 12 hours after administration of drugs under each regimen. All four regimens containing G-CSF caused greater than 10-fold increases in the ANC. When administered in conjunction with dexame thasone, G-CSF resulted in statistically similar PMN mobilization at dosage s of 450 mu g and 600 C1S The combined single-dose regimen of SC G-CSF at 4 50 mu g and PO dexamethasone at 8 mg increased the mean ANC from a baseline value of 2800 per mu L to 37,900 per mu L at 12 hours after administration . This regimen was well tolerated by the normal volunteers. CONCLUSION: In a single-dose format designed for clinical granulocyte trans fusion programs, optimal PMN mobilization can be achieved in normal donors with a combined regimen of SC G-CSF at 450 mu g, and PO dexamethasone at 8 mu g.