COMPARATIVE STUDIES OF GRANULOCYTE COLONY-STIMULATING FACTOR AND DEXAMETHASONE, A

治疗性粒细胞输注的效果受限于使用标准单采技术获得的细胞数量相对较少。为了确定一个最大限度地提高细胞产量，同时最大限度地减少供体不适的动员计划，我们研究了三种供体动员计划。献血者在捐献前12小时口服地塞米松（dexa） 8mg，采血前16-24小时口服粒细胞集落刺激因子（G-CSF） 5mg /kg SQ，或同样剂量的dexa +G -CSF （D+G）。7升全血在CS-3000 Plus设备上处理，使用Hetastarch作为沉淀剂。单独使用G-CSF或dexa +G -CSF联合使用导致产品中粒细胞含量比单独使用dexa增加2.3倍和3.5倍（分别从单独使用dexa的2.09 + 0.68增加到使用G-CSF和D+G的4.87 + 1.02和7.31 + 1.56 × 10的第10倍）（dexa与单独使用G-CSF或D+G相比p<0.01）。与单独的G-CSF相比，在G-CSF中添加dexa可使产物粒细胞含量增加49%。获得D+G的捐赠者中有72%患有骨痛、头痛、失眠或疲劳。10%的捐赠者要求停止参与研究，因为动员方案的不便和不适。30例临床中心患者接受了G-CSF动员粒细胞。20例深度中性粒细胞减少，包括8例严重再生障碍性贫血患者、6例干细胞移植患者、5例淋巴瘤患者和1例乳腺癌患者。其余10例为慢性肉芽肿病（CGD）。在中性粒细胞减少患者中，12例有全身丝状真菌感染，1例念珠菌感染，6例有细菌感染，1例有呼吸道合胞病毒感染。输血后1小时粒细胞计数平均增加2600/mL，并维持在500/mL以上12 ~ 24小时。在组织霉菌患者中，12名患者中有7名在粒细胞输注治疗期间病情稳定或改善，但12名患者中只有1名存活。相比之下，6例细菌过程中有3例出院。在10例CGD患者中，9例真菌（n=5）或细菌（n=5）感染完全消失；一名死亡的病人有大量的组织霉菌。这些G-CSF动员粒细胞的初步研究表明，它们可能会给精心挑选的有危及生命感染的中性粒细胞减少患者带来生存益处。为了回答这个问题，临床中心正在设计一项随机前瞻性研究，研究G-CSF动员粒细胞输注对住院治疗的严重再生障碍性贫血患者的疗效。

The efficacy of therapeutic granulocyte transfusions is limited by the rela-tively small number of cells obtained using standard apheresis techniques. To define a mobilization schedule that maximizes cell yields while minimizing donor discomfort, we studied three donor mobilization schedules. Donors received either dexamethasone (dexa) 8 mg orally 12 hours prior to donation, granulocyte colony-stimulating factor (G-CSF) 5 mg/kg SQ 16-24 hrs prior to apheresis, or dexa plus G- CSF (D+G) in the same doses. Seven liters of whole blood were processed on the CS-3000 Plus device using Hetastarch as the sedimenting agent. Administration of G-CSF alone or the combination of dexa plus G-CSF resulted in 2.3- and 3.5-fold increases in granulocyte content in the product compared to dexa alone (from 2.09 + 0.68 with dexa alone to 4.87 + 1.02 and 7.31 + 1.56 x10 to the 10th power cells total with G- CSF and D+G, respectively) (p<0.01 for dexa vs. G-CSF alone or D+G). Addition of dexa to G-CSF resulted in a 49 percent increase in product granulocyte content compared to G-CSF alone. 72 percent of donors getting D+G had had bone pain, headache, insomnia, or fatigue. Ten percent of donors requested discontinuation of participation in the study due to the inconvenience and discomfort of the mobilization regimen. Thirty Clinical Center patients have received G-CSF mobilized granulocytes. Twenty were profoundly neutropenic, including eight patients with severe aplastic anemia, six stem cell transplant recipients, five patients with lymphoma, and one with breast cancer. The remaining ten patients had chronic granulomatous disease (CGD). In the neutropenic patients, 12 had systemic filamentous fungal infections, one had candidemia, six had bac-terial infections, and one had RSV. The mean increment in granulocyte count one hour posttransfusion was 2600/mL, and counts above 500/mL were sustained for 12 to 24 hours. Of the patients with tissue molds, seven of 12 stabilized or improved during granulocyte transfusion therapy, but only one of 12 survived hospitalization. In contrast, 3 of 6 with bacterial processes were discharged from hospital. Of ten patients with CGD, nine had complete resolution of their fungal (n=5) or bacterial (n=5) infections; the one patient who expired had extensive tissue mold. These pilot studies of G-CSF mobilized granulocytes suggest that they may confer survival benefit in carefully selected neutropenic patients with life-threatening infections. A randomized prospective study of the efficacy of G-CSF mobilized granulocyte transfusions in patients with severe aplastic anemia hospitalized at the Clinical Center is being designed to answer this question.