Establishment of hemopoietic cytokine therapy for chronic neutropenia of childhood based on its pathogenic mechanism.

本研究旨在建立儿童慢性中性粒细胞减少症的造血细胞因子治疗方法。首先分析了中性粒细胞减少的机制，以制定更好的造血细胞因子治疗方案。然后，根据方案给予35例原发性中性粒细胞减少症患者、1例Ib型糖原蓄积性疾病患者和7例再生障碍性贫血患者造血细胞因子（M-CSF或G-CSF）。中性粒细胞减少的机制(1)原发性中性粒细胞减少和糖原蓄积病Ib型患者中性粒细胞祖细胞（GM-CFU）数量未见减少，表明细胞因子在这些疾病中促进祖细胞增殖的活性可能具有良好的临床作用。在再生障碍性贫血中，GM-CFU未被检测到或数量减少。这一发现提示造血细胞因子治疗在一些再生障碍性贫血患者中可能有良好的临床效果。(2)婴儿期慢性良性中性粒细胞减少症患者可检测到抗中性粒细胞抗体。预期造血细胞因子增加中性粒细胞数量可能降低抗体，导致中性粒细胞减少的早期改善。造血细胞因子治疗及临床效果(1)m - csf （6 × 10^6 U/m^2/d）静脉滴注，连续7 d。G-CSF （50 - 400mug/m^2/天）连续14天皮下注射（1例患者静脉注射）。Ib型糖原储存病患者随后给予维持治疗。(2)原发性中性粒细胞减少症：28例患者接受M-CSF治疗，其中19例获得充分数据；19例患者中有10例（52.6%）中性粒细胞计数增高。5例患者接受G-CSF治疗，所有患者中性粒细胞计数均升高。值得注意的是，2例先天性中性粒细胞减少患者的中性粒细胞计数明显增加（100 000/muL），顽固性感染均成功治疗。(3)糖原储存病Ib型，（6岁，男性）：G-CSF治疗可使中性粒细胞减少症和持续性感染恢复。通过每周两次G-CSF维持治疗（60马克/立方米/天），患者的中性粒细胞计数维持在1000毫升/毫升的水平，感染次数明显减少。(4)再生障碍性贫血：G-CSF治疗的7例患者中有4例中性粒细胞计数增加。一名患者在治疗期间抱怨骨痛，但其他患者没有副作用。少

The present study was conducted to establish hemopoietic cytokine therapy for chronic neutropenias of childhood. Mechanisms for neutropenia were first analyzed to make better protocols of hemopoietic cytokine therapy. Then, a hemopoigtic cytokine (M-CSF or G-CSF) was given based on the protocol to 35 patients with primary neutropenia, 1 with glycogen storage disease type Ib, and 7 with aplastic anemia.1. Mechanisms for neutropenia(1) There was no decrease in the number of neutrophil progenitor cells (GM-CFU) in primary neutropenia and glycogen storage disease type Ib, which indicated probable favorable clinical effects of the cytokines by their activity to promote proliferation of the progenitor cells in these disorders. In aplastic anemia, GM-CFU were not detectable or present in decreased numbers. This finding indicated possible favorable clinical effects of hemopoietic cytokine therapy in some patients with aplastic anemia.(2) Anti-neutrophil antibody was detectable in chronic benig … More n neutropenia of infancy. It was expected that an increase in neutrophil numbers by hemopoietic cytokines may decrease the antibody and result in earlier improvement of the neutropenia.2. Hemopoietic cytokine therapy and its clinical effects(1) M-CSF (6 X 10^6 U/m^2/day was administered by intravenous drip infusion for consecutive 7 days. G-CSF (50 - 400mug/m^2/day) was administered subcutaneously (intravenously in a patient) for consecutive 14 days or more. The patient with glycogen storage disease type Ib was placed on the maintenance therapy thereafter.(2) Primary neutropenia: Twenty-eight patients were given M-CSF, and sufficient data were obtained from 19 of them; there was an increase in neutrophil counts in 10 (52.6%) of the 19 patients. Five patients received G-CSF, and the neutrophil counts increased in all of them. It was noteworthy that there was an apparent increase ( >1,000/muL) in neutrophil counts, and intractable infections were successfully treated by the therapy in two of congenital neutropenia patients.(3) Glycogen storage disease type Ib,(6 yr, male): The G-CSF administration yielded a recovery from the neutropenia and persistent infections. His neutrophil counts are being maintained at levels of > 1,000/muL by twice/week of maintenance administration of G-CSF (60 mug/m^2/day), and infection episodes have been apparently decreased.(4,) Aplastic anemia: There was an increase in neutrophil counts in four of 7 patients who were treated with G-CSF. One patient complained bone pain during the therapy, but there were no side effects in the others. Less