Liles W C, Rodger E, Dale D C
Department of Medicine, University of Washington, Seattle, Washington 98195-7185, USA.
Transfusion. 2000 Jun;40(6):642-4. doi: 10.1046/j.1537-2995.2000.40060642.x.
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.
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.
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.
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.
中性粒细胞（多形核白细胞，PMN）输血治疗的临床效用受到一定影响，部分原因是无法从供体获取足够数量的功能性中性粒细胞。已表明，在正常志愿者外周血中动员PMN时，联合使用粒细胞集落刺激因子（G-CSF）和地塞米松比单独使用任何一种药物的效果更好。本研究旨在确定在粒细胞输血计划中给予供体的G-CSF和地塞米松的最佳剂量。
五名正常受试者在连续五周内被随机分配到以下每种单剂量方案中：1）皮下注射（SC）600微克G-CSF和口服（PO）8毫克地塞米松；2）皮下注射450微克G-CSF和口服8毫克地塞米松；3）皮下注射450微克G-CSF和口服12毫克地塞米松；4）皮下注射450微克G-CSF；5）口服12毫克地塞米松。在给药后0、6、12和24小时采集静脉血，用于测定绝对中性粒细胞计数（ANC）。使用标准化症状问卷记录药物给药的副作用。
在每种方案下，给药后12小时达到最大ANC。所有四种含G-CSF的方案均使ANC增加超过10倍。与地塞米松联合使用时，450微克和600微克剂量的G-CSF导致的PMN动员在统计学上相似。皮下注射450微克G-CSF和口服8毫克地塞米松的联合单剂量方案在给药后12小时将平均ANC从每微升2800的基线值提高到每微升37,900。该方案在正常志愿者中耐受性良好。
在为临床粒细胞输血计划设计的单剂量形式中，皮下注射450微克G-CSF和口服8微克地塞米松的联合方案可在正常供体中实现最佳的PMN动员。
