van der Wouw P A, van Leeuwen R, van Oers R H, Lange J M, Danner S A
Department of Internal Medicine (AIDS Unit), University of Amsterdam, The Netherlands.
Br J Haematol. 1991 Jul;78(3):319-24. doi: 10.1111/j.1365-2141.1991.tb04443.x.
Twelve male patients, eight with the acquired immunodeficiency syndrome (AIDS) and four with AIDS related complex (ARC), who had zidovudine associated neutropenia (less than 1 x 10(9) neutrophils/l) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) in a phase I/II study. Treatment consisted of daily subcutaneous injections with G-CSF in a weekly increasing dose of 0.4, 2, 5 or 10 micrograms/kg body weight until a neutrophil count of more than 3 x 10(9) neutrophils/l was observed. This effective dose was continued for up to 4 weeks, followed by 4 weeks observation period without G-CSF treatment. Two patients (both with ARC) reached target neutrophil counts at the lowest G-CSF dose, whereas nine patients needed 2 micrograms/kg. One patient discontinued treatment before he reached target neutrophil counts. Mean (+/- SD) neutrophil counts before and after 1 and 4 weeks of effective dose treatment were 0.65(+/- 0.188) x 10(9), 6.016(+/- 2.595) x 10(9) and 5.54(+/- 4.237) x 10(9)/l respectively (P less than 0.01). The number of monocytes increased from 0.171(+/- 0.113) to 0.501(+/- 0.274) and 0.474(+/- 0.374) x 10(9)/l after 1 and 4 weeks of treatment (P less than 0.01). Other haematologic parameters did not change significantly. Two weeks post-treatment the numbers of neutrophils and monocytes had returned to pre-treatment values. Mild side effects consisting of bone, joint or muscle pain were observed in three patients. Two patients (both with AIDS) did not complete the study. One patient stopped treatment because of fever and malaise, attributable to a generalized cytomegalovirus (CMV) infection and one patient had to stop zidovudine treatment because of severe thrombocytopenia. We conclude that G-CSF increases the number of circulating neutrophilic granulocytes in zidovudine-treated patients at relatively low doses and with few side-effects.
12名男性患者参与了一项I/II期研究，其中8名患有获得性免疫缺陷综合征（AIDS），4名患有艾滋病相关综合征（ARC），这些患者均出现了齐多夫定相关性中性粒细胞减少症（中性粒细胞计数低于1×10⁹/升），接受了重组人粒细胞集落刺激因子（G-CSF）治疗。治疗方法为每日皮下注射G-CSF，每周剂量递增，分别为0.4、2、5或10微克/千克体重，直至观察到中性粒细胞计数超过3×10⁹/升。达到有效剂量后持续治疗4周，随后为4周的无G-CSF治疗观察期。2名患者（均为ARC患者）在最低G-CSF剂量时达到了目标中性粒细胞计数，而9名患者需要2微克/千克的剂量。1名患者在达到目标中性粒细胞计数之前停止了治疗。有效剂量治疗1周和4周前后的平均（±标准差）中性粒细胞计数分别为0.65（±0.188）×10⁹、6.016（±2.595）×10⁹和5.54（±4.237）×10⁹/升（P<0.01）。治疗1周和4周后，单核细胞数量从0.171（±0.113）增加到0.501（±0.274）和0.474（±0.374）×10⁹/升（P<0.01）。其他血液学参数无明显变化。治疗后两周，中性粒细胞和单核细胞数量恢复到治疗前水平。3名患者出现了包括骨、关节或肌肉疼痛在内的轻度副作用。2名患者（均为AIDS患者）未完成研究。1名患者因发热和不适停止治疗，原因是全身性巨细胞病毒（CMV）感染，另1名患者因严重血小板减少症不得不停止齐多夫定治疗。我们得出结论，G-CSF能以相对低剂量且副作用较少的方式增加齐多夫定治疗患者循环中性粒细胞的数量。
