Hurst D, Kilpatrick L, Becker J, Lipani J, Kleman K, Perrine S, Douglas S D
Division of Hematology/Oncology, Children's Hospital Oakland, California.
Am J Pediatr Hematol Oncol. 1993 Feb;15(1):71-6. doi: 10.1097/00043426-199302000-00008.
Recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) was administered to two patients with glycogen storage disease, type 1b (GSD-1b), with chronic neutropenia, neutrophil dysfunction, and recurrent infections in an effort to increase neutrophil counts and increase resistance to infections.
The patients' baseline absolute neutrophil counts (ANC) ranged from 56 to 480 cells/mm3 despite increased granulocyte precursors in the bone marrow. GM-CSF was given s.c. at starting doses of 500 micrograms/m2/day divided into two doses.
After 48 h, ANC rose to 2,025 cells/mm3 and 3,132 cells/mm3, respectively. Absolute eosinophil counts also rose to 1,048 cells/mm3 (24%) and 4,820 cells/mm3 (33%) on days 10 and 9 in the two patients. Although an initial 10-day course of GM-CSF was tolerated in one patient without significant reactions, subsequent s.c. injections of GM-CSF were complicated by increasingly painful local reactions that necessitated discontinuation after 7 to 8 days. Intravenous infusion was associated with a febrile systemic reaction. Despite lack of improvement in neutrophil superoxide anion generation measured in one, both patients demonstrated unusually rapid healing of cutaneous infections on GM-CSF.
Our experience suggests that GM-CSF may be useful for short-term treatment of serious infections in GSD-1b. However, alternate dosage schedules or different preparations of GM-CSF to diminish local reactions would be required for long-term maintenance therapy. Granulocyte colony stimulating factor (G-CSF) has also been shown to increase neutrophils in this disease and has not been associated with allergic reactions.
对两名患有1b型糖原贮积病（GSD-1b）、慢性中性粒细胞减少、中性粒细胞功能障碍及反复感染的患者给予重组人粒细胞巨噬细胞集落刺激因子（GM-CSF），以提高中性粒细胞计数并增强抗感染能力。
尽管骨髓中粒细胞前体增加，但患者的基线绝对中性粒细胞计数（ANC）在56至480个细胞/mm³之间。GM-CSF开始以500微克/m²/天的剂量皮下注射，分两次给药。
48小时后，ANC分别升至2,025个细胞/mm³和3,132个细胞/mm³。两名患者在第10天和第9天时，绝对嗜酸性粒细胞计数也分别升至1,048个细胞/mm³（24%）和4,820个细胞/mm³（33%）。虽然一名患者耐受了最初为期10天的GM-CSF疗程且无明显反应，但随后皮下注射GM-CSF时出现了局部反应疼痛加剧的情况，7至8天后不得不停药。静脉输注则伴有发热性全身反应。尽管在其中一名患者中测得的中性粒细胞超氧化物阴离子生成没有改善，但两名患者在接受GM-CSF治疗时皮肤感染均愈合异常迅速。
我们的经验表明，GM-CSF可能对GSD-1b严重感染的短期治疗有用。然而，长期维持治疗需要采用替代给药方案或不同制剂的GM-CSF以减轻局部反应。粒细胞集落刺激因子（G-CSF）在该疾病中也已显示可增加中性粒细胞，且未出现过敏反应。
