粒细胞和粒细胞巨噬细胞集落刺激因子预防儿童血液肿瘤化疗后感染效果及安全性的前瞻性、多中心研究

Efficacy and safety of granulocyte and granulocyte-macrophage colony-stimulating factors for the prevention of post-chemotherapy infections in pediatric hematologic neoplasms:a prospective multi-center study

目的探讨重组人粒细胞巨噬细胞集落刺激因子(GM-CSF)和人粒细胞集落刺激因子(G-CSF)预防儿童血液肿瘤化疗后感染的有效性和安全性。方法收集2016年7月至2018年6月在6家三级甲等医院住院化疗的134例患儿,其中复旦大学附属儿科医院60例,上海交通大学医学院附属新华医院38例,苏州大学附属儿童医院29例,青岛大学医学院附属医院4例,西北妇女儿童医院2例,山东省千佛山医院1例。以随机数字表法将患儿分为GM-CSF组(38例)、G-CSF组(45例)、GM-CSF+G-CSF组(51例)。比较3组间感染、中性粒细胞绝对计数(ANC)恢复时间、血小板计数(Plt)降低以及不良反应发生情况。结果所有患儿化疗后骨髓抑制期共发生感染64例(47.8%),其中GM-CSF组18例(47.4%),G-CSF组20例(44.4%),GM-CSF+G-CSF组26例(51.0%);G-CSF组患儿呼吸道感染发生率高于GM-CSF组和GM-CSF+G-CSF组[22.2%(10/45)比2.6%(1/38)、4.0%(2/51),χ^(2)=12.00,P=0.002]。所有患儿ANC恢复至≥1.5×10^(9)/L的中位时间为10.5 d(8 d,15 d),其中GM-CSF组为12 d(10 d,16 d),G-CSF组为9 d(8 d,12 d),GM-CSF+G-CSF组为10 d(8 d,16 d)。所有患儿中101例(75.4%)骨髓抑制期Plt<50×10^(9)/L,79例(59.0%)Plt<20×10^(9)/L。3组间Plt<50×10^(9)/L和<20×10^(9)/L的发生率差异均无统计学意义(均P>0.05)。所有患儿中24例(17.9%)发生不良反应,包括发热20例(14.9%),咽痛2例(1.5%),恶心1例(0.7%),腹泻1例(0.7%);未发生2级以上不良反应。3组间不良反应发生率比较,差异无统计学意义(P>0.05)。结论GM-CSF和G-CSF预防儿童血液肿瘤化疗后骨髓抑制期感染的效果相当,二者联用耐受性较好。单用GM-CSF及其与G-CSF联用的呼吸道感染发生率较低,可能与GM-CSF对肺部感染起作用有关。

Objective To explore the efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor(GM-CSF)and human granulocyte colony-stimulating factor(G-CSF)for the prevention of post-chemotherapy infections in pediatric hematologic neoplasms.Methods A total of 134 children hospitalized for chemotherapy in 6 tertiary hospitals from July 2016 to June 2018 were collected,including 60 cases in Children's Hospital of Fudan University,38 cases in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,29 cases in Children's Hospital Affiliated to Soochow University,4 cases in the Affiliated Hospital of Qingdao University,2 cases in Northwestern Women and Children's Hospital,and 1 case in Shandong Provincial Qianfoshan Hospital.The children were divided into GM-CSF group(38 cases),G-CSF group(45 cases)and GM-CSF+G-CSF group(51 cases)by using random number table method.The incidence of infections,the recovery time of absolute neutrophil counting(ANC),the decrease of blood platelet count(Plt)and the incidence of adverse reactions were compared among the three groups.Results In all children,a total of 64 cases(47.8%)had infections during the myelosuppression phase after chemotherapy,of which 18 cases(47.4%)in GM-CSF group,20 cases(44.4%)in G-CSF group,and 26 cases(51.0%)in GM-CSF+G-CSF group.The incidence of respiratory infection in G-CSF group was higher than that in GM-CSF group and GM-CSF+G-CSF group[22.2%(10/45)vs.2.6%(1/38),4.0%(2/51),χ^(2)=12.00,P=0.002].The median time to recovery of ANC>1.5×10^(9)/L was 10.5 d(8 d,15 d)in all children,12 d(10 d,16 d)in GM-CSF group,9 d(8 d,12 d)in G-CSF group,and 10 d(8 d,16 d)in GM-CSF+G-CSF group.In all children,a total of 101 cases(75.4%)had Plt<50×10^(9)/L during the myelosuppression phase,and 79 cases(59.0%)had Plt<20×10^(9)/L.The differences in the incidence of Plt<50×10^(9)/L and<20×10^(9)/L among the three groups were not statistically significant(both P>0.05).In all children,the adverse reactions occurred in 24 cases(17.9%),including 20 cases(14.9%)of fever,2 cases(1.5%)of sore throat,1 case(0.7%)of nausea,and 1 case(0.7%)of diarrhea;no adverse reactions of grade 2 or above occurred.The difference in the incidence of adverse reactions among the three groups was not statistically significant(P>0.05).Conclusions The efficacy of GM-CSF and G-CSF for the prevention of infections in pediatric hematologic neoplasms during the myelosuppression phase after chemotherapy is roughly equivalent,and combination of both has a good tolerance.The incidence of respiratory infection using GM-CSF alone or GM-CSF+G-CSF is low,which might benefit from the effect of GM-CSF on lung infections.