聚乙二醇化重组人粒细胞集落刺激因子在儿童急性淋巴细胞白血病的药代动力学和药效学的前瞻性对照研究

目的 探讨聚乙二醇化重组人粒细胞集落刺激因子（PEG-rhG-CSF）在儿童急性淋巴细胞白血病（ALL）患者中的药代动力学特征，分析其疗效与安全性。方法 前瞻性纳入拟使用环磷酰胺、阿糖胞苷和6-巯基嘌呤巩固治疗的儿童ALL患者，化疗结束后注射PEG-rhG-CSF（PEG-rhG-CSF组）或重组人粒细胞集落刺激因子（rhG-CSF组）。检测PEG-rhG-CSF血药浓度，同时观察两组患儿的疗效及安全性。结果 共纳入17例（PEG-rhG-CSF组9例，rhG-CSF组8例）ALL患儿。PEG-rhG-CSF组患儿峰浓度（Cmax）为348.2（范围114.7~552.0）ng/mL，达峰时间（Tmax）为48.0（范围12.0~72.0）h，半衰期（t1/2）为14.1（范围11.1~18.1）h。血药浓度曲线符合中性粒细胞介导清除机制。与rhG-CSF组相比，PEG-rhG-CSF组患儿中性粒细胞绝对值恢复正常的时间更早（P < 0.05）。两组患儿中性粒细胞绝对值最低点、中性粒细胞缺乏伴发热发生率、Ⅲ/Ⅳ度粒细胞缺乏发生率、Ⅳ度粒细胞缺乏持续时间、感染发生情况及住院时间差异均无统计学意义（P > 0.05）。两组患儿均未发生骨骼、肌肉酸痛。结论 PEG-rhG-CSF在接受巩固化疗的儿童ALL患者中药代动力学特征符合中性粒细胞介导清除机制，半衰期短，中性粒细胞恢复更快。与rhG-CSF相比，安全性无明显差异。

Pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a prospective control trial

Objective To study the pharmacokinetic characteristics, clinical effect, and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in children with acute lymphoblastic leukemia (ALL). Methods A prospective study was performed on children with ALL who cyclophosphamide, cytarabine, and 6-mercaptopurine were used for consolidation therapy. PEG-rhG-CSF (PEG-rhG-CSF group) or rhG-CSF (rhG-CSF group) was injected after chemotherapy. The plasma concentration of PEG-rhG-CSF was measured, and clinical outcome and safety were observed for both groups. Results A total of 17 children with ALL were enrolled, with 9 children in the PEG-rhG-CSF group and 8 children in the rhG-CSF group. In the PEG-rhG-CSF group, the peak concentration of PEG-rhG-CSF was 348.2 ng/mL (range 114.7-552.0 ng/mL), the time to peak was 48 hours (range 12-72 hours), and the half life was 14.1 hours (range 11.1-18.1 hours). The plasma concentration curve of PEG-rhG-CSF was consistent with the mechanism of neutrophil-mediated clearance. Compared with the rhG-CSF group, the PEG-rhG-CSF group had a significantly shorter median time to absolute neutrophil count (ANC) recovery (P < 0.05). There were no significant differences between the two groups in ANC nadir, incidence rate of febrile neutropenia, duration of grade IV neutropenia, incidence rate of infection, and length of hospital stay. No bone pain or muscle soreness was observed in either group (P > 0.05). Conclusions The pharmacokinetic characteristics of PEG-rhG-CSF in children with ALL receiving consolidation chemotherapy are consistent with the mechanism of neutrophil-mediated clearance, with a short half life and fast recovery of ANC, and there are no significant differences in safety between PEG-rhG-CSF and rhG-CSF.