Bonilla M A, Gillio A P, Ruggeiro M, Kernan N A, Brochstein J A, Abboud M, Fumagalli L, Vincent M, Gabrilove J L, Welte Karl, Souza Lawrence M, O'Reilly Richard J
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
N Engl J Med. 1989 Jun 15;320(24):1574-80. doi: 10.1056/NEJM198906153202402.
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 micrograms 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 cells 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.
先天性粒细胞缺乏症是一种以严重中性粒细胞减少和骨髓中可识别的中性粒细胞祖细胞严重缺乏为特征的疾病。为了刺激中性粒细胞的产生，从而降低与该疾病相关的发病率和死亡率，我们对5例先天性粒细胞缺乏症患者每天给予3至60微克/千克体重的重组人粒细胞集落刺激因子（rhG-CSF）。在所有5例患者中，开始有效剂量（中性粒细胞计数达到每微升1000个细胞或更多且骨髓显示粒细胞成熟超过中幼粒细胞阶段的剂量）后8至9天，中性粒细胞数量增加。绝对中性粒细胞计数从每微升少于100个升至每微升1300至9500个。在有效剂量下14天后获取的骨髓抽吸物显示成熟至成熟中性粒细胞阶段。观察到的副作用有骨髓疼痛、脾肿大和白细胞碱性磷酸酶水平升高。所有5例患者在接受皮下维持治疗期间，中性粒细胞计数持续保持在每微升1000个细胞或更多达9至13个月。先前存在的慢性感染在临床上已得到缓解，新感染发作的次数和静脉使用抗生素的需求减少。我们得出结论，rhG-CSF治疗可使先天性粒细胞缺乏症患者功能性中性粒细胞数量大幅增加。
