北京儿童医院改良噬血细胞性淋巴组织细胞增生症04方案疗效及安全性评价

Efficacy and safety of modified hemophagocytic lymphohistiocytosis 04 regimen in Beijing Children′s Hospital

目的:评价北京儿童医院(BCH)改良噬血细胞性淋巴组织细胞增生症(HLH)04方案的疗效及安全性。方法:回顾性队列研究。将2016年1月至2017年12月北京儿童医院血液肿瘤中心收治的采用BCH改良HLH-04方案(诱导期将地塞米松替换为甲泼尼龙、减低依托泊苷的剂量和频次、除自身免疫相关HLH外不使用环孢素)治疗的110例HLH患儿作为改良组,将2012年1月至2015年12月该中心收治的应用标准HLH-04方案治疗的102例HLH患儿作为对照组,对两组的早期缓解率、生存率、不良反应等方面进行比较分析。组间比较采用秩和检验或χ^(2)检验。结果:改良组患儿发病年龄为1.9(1.1,3.5)岁,男65例,女45例;对照组发病年龄为2.0(1.2,4.6)岁,男47例,女55例。两组患儿在发病年龄及性别上,差异均无统计学意义(均P>0.05)。除纤维蛋白原[1.3(1.0,1.7)比1.1(0.8,1.4)g/L,Z=-2.67,P=0.008]、自然杀伤细胞活性[13.9(13.4,16.3)%比14.9(12.0,16.1)%,Z=-2.34,P=0.028]之外,两组患儿在病因、病程、首发临床表现、实验室检查等方面差异均无统计学意义(均P>0.05)。改良组与对照组患儿2个月、3年总生存率差异均无统计学意义[84.5%(93/110)比76.5%(78/102),78.2%(86/110)比67.6%(69/102),χ^(2)=2.28、3.07,P=0.131、0.080]。骨髓抑制主要发生于前3周,发生率低于对照组[47.3%(52/110)比62.7%(64/102),χ^(2)=5.11,P=0.024]。与对照组相比,改良组真菌感染率较低[3.6%(4/110)比13.7%(14/102),χ^(2)=6.93,P=0.008]。改良组死于化疗后不良反应的患儿较少[8.0%(2/25)比30.3%(10/33),χ^(2)=4.31,P=0.038]。结论:BCH改良HLH-04方案减低了化疗强度,总体疗效不劣于标准HLH-04方案,明显降低了化疗相关骨髓抑制率、真菌感染率和病死率。

Objective To evaluate the efficacy and safety of Beijing Children′s Hospital(BCH)modified hemophagocytic lymphohistiocytosis(HLH)04 regimen in the treatment of childhood HLH.Methods A retrospective cohort study was conducted.From January 2016 to December 2017,110 children with HLH who were treated with the modified HLH-04 regimen(replacing dexamethasone with methylprednisolone during the induction period,reducing the dose and frequency of etoposide,and not using cyclosporine except for autoimmune-related HLH)at the Hematology Oncology Center of Beijing Children′s Hospital were selected as the modified group,while 102 children treated with the standard HLH-04 regimen from January 2012 to December 2015 were selected as the control group.The early remission rate,survival rate and adverse reactions of two groups were compared.Rank sum test and chi square test were used for comparison between groups.Results The age of onset in the modified group was 1.9(1.1,3.5)years,with 65 males and 45 females.The age of onset in the control group was 2.0(1.2,4.6)years,with 47 males and 55 females.No significant difference was found in age and gender between 2 groups(both P>0.05).Except for fibrinogen(1.3(1.0,1.7)vs.1.1(0.8,1.4)g/L,Z=-2.67,P=0.008)and natural killer cell activity(13.9(13.4,16.3)%vs.14.9(12.0,16.1)%,Z=-2.34,P=0.028),there were no statistically significant differences in etiology,disease duration,first clinical presentation,or laboratory tests between 2 groups(all P>0.05).At 2 months and 3 years,there were no statistically significant differences in overall survival between 2 groups(84.5%(93/110)vs.76.5%(78/102),78.2%(86/110)vs.67.6%(69/102),χ^(2)=2.28,3.07,P=0.131,0.080).The first 3 weeks were the most common time for bone marrow suppression in the modified group,with a lower incidence than in the control group(47.3%(52/110)vs.62.7%(64/102),χ^(2)=5.11,P=0.024).The modified group had a lower rate of fungal infections than the control group(3.6%(4/110)vs.13.7%(14/102),χ^(2)=6.93,P=0.008).Compared with the control group,fewer children in the modified group died as a result of side effects from chemotherapy(8.0%(2/25)vs.30.3%(10/33),χ^(2)=4.31,P=0.038).Conclusion The BCH modified HLH-04 regimen reduced the intensity of chemotherapy,with overall efficacy no worse than the standard HLH-04 regimen,and significantly reduced the rate of chemotherapy-related myelosuppression,fungal infection and mortality.