聚乙二醇化重组人粒细胞刺激因子预防儿童急性淋巴细胞白血病化疗后中性粒细胞减少的临床观察

Clinical observation of pegylated recombinant human granulocyte colony-stimulating factor to prevent the chemotherapy-induced neutropenia in children with acute lymphoblastic leukemia

目的观察聚乙二醇化重组人粒细胞刺激因子(PEG-rhG-CSF)预防儿童急性淋巴细胞白血病(ALL)化疗后中性粒细胞减少的临床效果及安全性。方法回顾性分析北京大学人民医院儿科2018-06-13-2019-06-27 25例ALL患儿接受大剂量阿糖胞苷联合伊达比星方案(IA方案)化疗后PEG-rhG-CSF组和普通重组人粒细胞集落刺激因子(rhG-CSF)组的临床资料,对2组患儿中性粒细胞减少症的程度、持续时间、发热性中性粒细胞减少症(FN)和不良反应等进行比较。结果 25例ALL患儿均为B细胞型ALL。在40轮IA化疗中,应用PEG-rhG-CSF组(20轮)与应用普通rhG-CSF组(20轮)的中性粒细胞最低值(U=150.5,P=0.173)及Ⅳ度中性粒细胞减少开始时间(U=182.0,P=0.817)差异无统计学意义。PEG-rhG-CSF组患儿Ⅳ度中性粒细胞减少恢复时间及持续时间分别为(10.58±0.90)、(3.95±1.88) d,均短于rhG-CSF组的(12.65±1.98)和(6.25±2.07) d,差异有统计学意义,U值分别为64.0和79.0,P值分别为0.006和0.001。PEG-rhG-CSF组患儿使用普通rhG-CSF的天数(3.0±0.97) d少于rhG-CSF组的(6.25±2.07) d,差异有统计学意义,U=23.0,P=0.013。PEG-rhG-CSF和rhG-CSF组患儿的FN发生率分别为30%(6/20)和20%(4/20),差异无统计学意义,χ2=0.533,P=0.716。最常见的不良反应包括骨痛及白细胞过高。PEG-rhG-CSF组患儿白细胞过高发生率为70%(14/20),高于rhG-CSF组的20%(4/20),χ2=10.101,P=0.004。结论在儿童ALL强化疗后预防性使用PEG-rhG-CSF能缩短Ⅳ度中性粒细胞减少时间,减少普通rhG-CSF的使用,且安全性较好,在临床实践中具有应用前景。

Objective To detect the effect and safety of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in preventing the chemotherapy-induced neutropenia in children with acute lymphoblastic leukemia(ALL).Methods We retrospectively collected and analyzed the clinical data in PEG-rhG-CSF group and recombinant human granulocyte colony-stimulating factor(rhG-CSF) group of 25 ALL children after high-dose cytarabine combined with idabisin regimen(IA regimen) chemotherapy in department of pediatrics,Peking University People’s Hospital between June 13,2018 and June 27,2019.The severity and duration of neutropenia,the rate of febrile neutropenia(FN) and adverse reactions were compared between two groups.Results All 25 children were diagnosed with B-ALL.In 40 cycles of IA,the two groups(20 cycles each) had no statistical difference in the lowest absolute value of neutrophils(U=150.5,P=0.173) and the onset time of degree Ⅳ neutropenia(U=182.0,P=0.817).The recovery time and duration of Ⅳ degree neutropenia in PEG-rhG-CSF group were(10.58±0.90)days and(3.95±1.88)days respectively,both were shorter than those in rhG-CSF group,which were(12.65±1.98)days(U=64.0,P=0.006)and(6.25±2.07)days(U=79.0,P=0.001).Children in PEG-rhG-CSF group used rhG-CSF for(3.0±0.97)days that was less than rhG-CSF group which was(6.25±2.07)days,and the difference was statistically significant(U =23.0,P=0.013).The incidence of FN of PEG-rhG-CSF group was 30%(6/20)and rhG-CSF group was 20%(4/20)with no significant difference between the two groups(x^(2)=0.533,P=0.716).The most common adverse reactions included bone pain and leukocyte overshoot.The incidence of leukocyte overshoot in PEG-rhG-CSF group was 70%(14/20),higher than that in rhG-CSF group which was20%(4/20;x^(2)=10.101,P=0.004).Conclusions After high dose chemotherapy,the preventive use of PEG-rhG-CSF in ALL children can shorten the duration of neutropenia and reduce the use of rhG-CSF,and the process is also quite safe.PEG-rhG-CSF has an application prospect in clinical practice.