聚乙二醇化重组人G-CSF促进淋巴瘤患者自体造血干细胞移植后造血重建的效果及安全性

Effect and safety of pegylated recombinant human G-CSF on hematopoietic reconstitution after autologous hematopoietic stem cell transplantation in lymphoma patients

目的观察聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)在淋巴瘤患者自体造血干细胞移植(auto-HSCT)后促进造血重建的效果及安全性。方法对2016年4月至2021年12月上海交通大学医学院附属瑞金医院149例接受auto-HSCT的淋巴瘤患者进行回顾性分析。75例于移植后第1、8天分别给予PEG-rhG-CSF 100μg/kg皮下注射1次;74例于移植后第1天开始予以重组人粒细胞集落刺激因子(rhG-CSF)5~10µg·kg^(-1)·d^(-1)皮下注射,至中性粒细胞绝对计数(ANC)>1.5×10^(9)/L持续3 d停药。结果①PEG-rhG-CSF组、rhG-CSF组中性粒细胞植入时间分别为9.5(7~17)d、10(8~22)d(P=0.007),3级粒细胞缺乏持续时间分别为2(0~7)d、1.5(0~4)d(P=0.030),4级粒细胞缺乏持续时间分别为9(5~16)d、9.5(6~23)d(P=0.010);血小板植入时间、Ⅳ级贫血发生率及持续时间及移植后1个月内血小板输注量、红细胞输注量差异均无统计学意义(P值均>0.05)。②PEG-rhG-CSF组、rhG-CSF组粒细胞缺乏伴发热的发生率分别为84.0%(63/75)、82.4%(61/74)(P=0.798),中位持续时间分别为4(1~10)d、5.5(1~24)d(P=0.005)。③PEG-rhG-CSF组、rhG-CSF组感染发生率分别为22.7%(17/75)、31.1%(23/74)(P=0.247),血流感染发生率分别为5.3%(4/75)、9.5%(7/74)(P=0.336)。④PEG-rhG-CSF组、rhG-CSF组住院天数分别为31.5(23~43)d、37(25~75)d(P<0.001)。⑤PEG-rhG-CSF组、rhG-CSF组移植后6个月无病生存(DFS)率分别为(96.4±2.5)%、(94.7±2.6)%(P=0.638),总生存(OS)率分别为100.0%、(98.6±1.3)%(P=0.312)。结论淋巴瘤患者auto-HSCT后应用PEG-rhG-CSF在促进中性粒细胞植入、缩短粒细胞缺乏伴发热持续时间方面优于rhG-CSF,移植后感染发生率、移植后6个月DFS率及OS率与rhG-CSF无显著差异。

Objective Efficacy and safety analysis of pegylated recombinant human granulocyte colony stimulating factor(PEG-rhG-CSF)in promoting hematopoietic recovery after autologous hematopoietic stem cell transplantation(auto-HSCT)in patients with lymphoma.Methods A total of 149 patients after auto-HSCT in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled in this study from April 2016 to December 2021.There were 75 cases in the PEG-rhG-CSF group who were given a single subcutaneous dose of 100µg/kg on the first day and+8 d,while 74 cases in the rhG-CSF group were given a dose of 5-10µg·kg^(-1)·d^(-1) by subcutaneous injection from+1d continuing to an absolute value of neutrophil(ANC)of more than 1.5×10^(9)/L.Results①The time of grade 3/4 agranulocytosis and neutrophil implantation in the PEG-rhG-CSF group were significantly different from that in rhG-CSF group(P=0.010,0.030,0.007).There were no significant differences in the platelet implantation time,anemia incidence and duration,and platelet and red blood cell infusion within 1 month after transplantation between groups.②The agranulocytosis with fever incidence in PEG-rhG-CSF group was similar to that in rhG-CSF group(84.0%vs 82.4%,P=0.798),but the duration was shorter in the PEG-rhG-CSF group(4.0 d vs 5.5 d,P=0.005).③The incidence of infection in the PEG-rhG-CSF and the rhG-CSF groups were 22.7%(17/75)and 31.1%(23/74),respectively(P=0.247),and the bloodstream infection incidence were 5.3%(4/75)and 9.5%(7/74),respectively(P=0.336).④The PEG-rhG-CSF group and rhG-CSF group’s mean length of hospital stay were 31.5(23-43)days and 37(25-75)days,respectively(P<0.001).⑤The PEG-rhG-CSF group and rhG-CSF group’s disease-free survival rates were(96.4±2.5)%and(94.7±2.6)%(P=0.638),respectively,and the OS rates were 100.0%and(98.6±1.3)%(P=0.312),respectively.Conclusion PEG-rhG-CSF application after auto-HSCT in patients with lymphoma can promote hematopoietic granulocyte reconstruction and shorten hospital stay,but has no significant effect on the incidence of infection,disease-free survival,and overall survival after transplantation.