PMID- 10864982 OWN - NLM STAT- MEDLINE DCOM- 20000912 LR - 20220330 IS - 0041-1132 (Print) IS - 0041-1132 (Linking) VI - 40 IP - 6 DP - 2000 Jun TI - Combined administration of G-CSF and dexamethasone for the mobilization of granulocytes in normal donors: optimization of dosing. PG - 642-4 AB - 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. Mobilization of PMNs in the peripheral blood of normal volunteers has been shown to be superior when G-CSF is administered in conjunction with dexamethasone to that when either agent is administered alone. The current study was conducted 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 each of the following single-dose regimens over five consecutive weeks: 1) subcutaneous (SC) G-CSF at 600 microg and oral (PO) dexamethasone at 8 mg; 2) SC G-CSF at 450 microg and PO dexamethasone at 8 mg; 3) SC G-CSF at 450 microg and PO dexamethasone at 12 mg; 4) SC G-CSF at 450 microg; and 5) PO dexamethasone at 12 mg. Venous blood was collected at 0, 6, 12, and 24 hours after drug administration for determination of absolute neutrophil count (ANC). Side effects of drug administration were recorded by using a standardized symptom 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 dexamethasone, G-CSF resulted in statistically similar PMN mobilization at dosages of 450 microg and 600 microg. The combined single-dose regimen of SC G-CSF at 450 microg and PO dexamethasone at 8 mg increased the mean ANC from a baseline value of 2800 per microL to 37,900 per microL at 12 hours after administration. This regimen was well tolerated by the normal volunteers. CONCLUSION: In a single-dose format designed for clinical granulocyte transfusion programs, optimal PMN mobilization can be achieved in normal donors with a combined regimen of SC G-CSF at 450 microg, and PO dexamethasone at 8 microg. FAU - Liles, W C AU - Liles WC AD - Department of Medicine, University of Washington, Seattle, Washington 98195-7185, USA. FAU - Rodger, E AU - Rodger E FAU - Dale, D C AU - Dale DC LA - eng PT - Clinical Trial PT - Comparative Study PT - Controlled Clinical Trial PT - Journal Article PL - United States TA - Transfusion JT - Transfusion JID - 0417360 RN - 0 (Recombinant Proteins) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - 7S5I7G3JQL (Dexamethasone) SB - IM MH - Administration, Oral MH - Adolescent MH - Adult MH - *Blood Donors MH - Dexamethasone/administration & dosage/adverse effects/*pharmacology MH - Female MH - Granulocyte Colony-Stimulating Factor/administration & dosage/adverse effects/*pharmacology MH - *Granulocytes MH - Humans MH - Injections, Subcutaneous MH - Leukocyte Count/*drug effects MH - Male MH - Middle Aged MH - Pain/chemically induced MH - Recombinant Proteins/administration & dosage/adverse effects/pharmacology MH - Sleep Initiation and Maintenance Disorders/chemically induced EDAT- 2000/06/24 11:00 MHDA- 2000/09/19 11:01 CRDT- 2000/06/24 11:00 PHST- 2000/06/24 11:00 [pubmed] PHST- 2000/09/19 11:01 [medline] PHST- 2000/06/24 11:00 [entrez] AID - 10.1046/j.1537-2995.2000.40060642.x [doi] PST - ppublish SO - Transfusion. 2000 Jun;40(6):642-4. doi: 10.1046/j.1537-2995.2000.40060642.x.