EFFECTS OF RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR ON NEUTROPENIA IN PATIENTS WITH CONGENITAL AGRANULOCYTOSIS
EFFECTS OF RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR ON NEUTROPENIA IN PATIENTS WITH CONGENITAL AGRANULOCYTOSIS
复制标题
DOI：
10.1056/nejm198906153202402
复制
发表时间：
1989-06-15
影响因子：
158.5
通讯作者：
OREILLY, RJ
中科院分区：
文献类型：
--
作者：
BONILLA, MA;GILLIO, AP;OREILLY, RJ
先天性粒细胞缺乏症是一种以严重的中性粒细胞减少和骨髓中可识别的中性粒细胞前体细胞严重缺乏为特征的疾病。为了刺激中性粒细胞的产生，从而降低与这种疾病相关的发病率和死亡率，我们给5名先天性粒细胞缺乏症患者注射重组人粒细胞集落刺激因子(rhG-CSF)，剂量为每公斤体重每天3-60微克。在所有5名患者中，中性粒细胞数量在开始有效剂量(中性粒细胞计数达到或超过每微升1000个细胞，并且骨髓显示粒细胞成熟超过髓细胞阶段的剂量)后8至9天出现增加。中性粒细胞的绝对计数从每微升不到100个增加到1300到9500个细胞。在有效剂量下14天后获得的骨髓抽吸物显示成熟到成熟的中性粒细胞阶段。观察到的副作用包括髓样疼痛、脾肿大和白细胞碱性磷酸酶水平升高。在接受皮下维持治疗期间，所有五名患者的中性粒细胞计数都保持在每微升1000个细胞或更多，持续了9到13个月。先前存在的慢性感染已在临床上得到解决，新感染病例的数量和静脉注射抗生素的需求也有所减少。我们的结论是，在先天性粒细胞缺乏症患者中，应用重组人粒细胞集落刺激因子可导致功能性中性粒细胞数量的显著增加。
Congenital agranulocytosis is a disorder characterized by severe neutropenia and a profound deficiency of identifiable neutrophil progenitors in bone marrow. In an attempt to stimulate neutrophil production and thereby reduce the morbidity and mortality associated with this disease, we administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) in doses of 3 to 60 .mu.g per kilogram of body weight per day to five patients with congenital agranulocytosis. In all five patients, an increase in the number of neutrophils was noted eight to nine days after the initiation of the effective dosage (the dose at which the neutrophil count reached 1000 cells per microliter or more and the bone marrow showed granulocyte maturation beyond the myelocyte stage). The absolute neutrophil counts rose from less than 100 to between 1300 and 9500 cells per microliter. Marrow aspirates obtained after 14 days at the effective dosage showed maturation to the mature neutrophil stage. The side effects that were observed were medullary pain, splenomegaly, and an elevation of levels of leukocyte alkaline phosphatase. All five patients have had sustained neutrophil counts of 1000 cell per microliter or more for 9 to 13 months while receiving subcutaneous maintenance therapy. Preexisting chronic infections have resolved clinically, and the number of new infectious episodes and the requirement for intravenous antibiotics have decreased. We conclude that treatment with rhG-CSF can lead to a large increase in the numbers of functional neutrophils in patients with congenital agranulocytosis.