Therapeutic Efficacy Of Granulocyte Colony-stimulating F

治疗性粒细胞输注的效果受限于使用标准分离技术获得的细胞数量相对较少。在先前的研究中，我们证明了通过粒细胞集落刺激因子（G-CSF）或G-CSF与地塞米松（dexa）联合刺激供体制备的粒细胞浓缩物比单独使用地塞米松制备的产物含有2.3倍和3.5倍的粒细胞数量(地塞米松单独制备的产物含量为2.09 × 10e10个细胞，而G-CSF和G-CSF加dexa制备的产物含量为4.87和7.31 × 10e10个细胞。dexa与单独使用G-CSF或G-CSF加dexa相比p < 0.01)。接受G-CSF加dexa治疗的献血者中，72%的人有躁动、失眠、骨痛或头痛。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。56名临床中心患者接受了G-CSF动员粒细胞。重度中性粒细胞减少35例，其中重度再生障碍性贫血15例，干细胞移植患者12例，淋巴瘤/白血病7例，乳腺癌1例。其余21例为CGD。在中性粒细胞减少患者中，21例有全身丝状真菌感染，11例有细菌感染，2例有念珠菌感染，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/uL，高于基线500/uL的粒细胞计数持续12 ~ 24小时。在粒细胞输注后存活超过2周的14例中性粒细胞减少、免疫抑制患者中，有1例发生HLA异敏化，15例CGD患者中有2例发生HLA异敏化。在没有HLA异敏化的情况下，粒细胞输注与进行性缺氧、肺浸润和ards样事件相关，15例SAA患者中有4例，而21例CGD患者中有1例。在嗜中性粒细胞减少的组织霉菌患者中，21例患者中有10例在粒细胞输注治疗期间病情稳定或好转，但21例患者中只有5例存活。相比之下，11例有细菌过程的患者中有5例出院。21例CGD患者中有18例真菌感染（12例中有9例）或细菌感染（9例中有9例）得到解决。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中性粒细胞减少患者带来生存益处，但可能与显著的进行性肺毒性有关。NHLBI止血/输血医学临床试验网络正在组织一项随机前瞻性多中心研究，研究G-CSF动员粒细胞输注对丝状真菌感染的严重中性粒细胞减少患者的疗效。

The efficacy of therapeutic granulocyte transfusions is limited by the relatively small number of cells obtained using standard apheresis techniques. In prior studies, we demonstrated that granulocyte concentrates prepared by granulocyte-colony stimulating factor (G-CSF) or the combination of G-CSF and dexamethasone (dexa) stimulation of the donor contained 2.3- and 3.5-fold greater numbers of granulocytes than products prepared using dexamethasone alone (product content 2.09 x 10e10 cells with dexamethasone alone versus 4.87 and 7.31 x 10e10 cells total with G-CSF and G-CSF plus dexa, respectively) (p less than 0.01 for dexa vs G-CSF alone or G-CSF plus dexa). Seventy-two percent of donors getting G-CSF plus dexa had restlessness, insomnia, bone pain, or headache. Ten percent of donors requested discontinuation of participation in the study due to the inconvenience and discomfort of the mobilization regimen. Fifty-six Clinical Center patients have received G-CSF mobilized granulocytes. Thirty-five were profoundly neutropenic, including 15 patients with severe aplastic anemia (SAA), 12 stem cell transplant recipients, 7 patients with lymphoma/leukemia, and 1 with breast cancer. The remaining 21 patients had CGD. In the neutropenic patients, 21 had systemic filamentous fungal infections, 11 had bacterial infections, two had candidemia and one had RSV infection. The mean increment in granulocyte count 1-hour post-transfusion was 2600/uL, and counts greater than 500/uL above baseline were sustained for 12 to 24 hours. One of the 14 neutropenic, immunosuppressed patients who survived longer than 2 weeks after the initiation of granulocyte transfusions developed HLA allosensitization, as did two of the 15 CGD patients. In the absence of HLA allosensitization, granulocyte transfusions were associated with progressive hypoxia, pulmonary infiltrates, and an ARDS-like event in four of 15 SAA patients, versus one of 21 CGD patients. Of the neutropenic patients with tissue molds, 10 of 21 stabilized or improved during granulocyte transfusion therapy, but only 5 of 21 survived hospitalization. In contrast, five of 11 with bacterial processes were discharged from hospital. Eighteen of 21 patients with CGD had resolution of their fungal (9 of 12) or bacterial (9 of 9) infections. These pilot studies of G-CSF mobilized granulocytes suggest that they may confer survival benefit in carefully selected neutropenic patients with life-threatening infections, but may be associated with significant progressive pulmonary toxicity. A randomized prospective multicenter study of the efficacy of G-CSF mobilized granulocyte transfusions in severely neutropenic patients with filamentous fungal infections is being organized by the Hemostasis/Transfusion Medicine Clinical Trials Network of NHLBI.