血浆及全血EB病毒DNA对EB病毒相关噬血细胞性淋巴组织细胞增生症患儿预后的影响  

Prognostic significance of plasma and whole blood Epstein-Barr virus-DNA load during treatment in children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis

作　　者：张晴 崔蕾 马宏浩 王冬 赵云泽 王天有 李志刚 张蕊 Zhang Qing;Cui Lei;Ma Honghao;Wang Dong;Zhao Yunze;Wang Tianyou;Li Zhigang;Zhang Rui(Laboratory of Hematologic Diseases,Beijing Pediatric Research Institute,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China;Beijing Key Laboratory of Pediatric Hematology Oncology,Key Laboratory of Major Diseases in Children,Ministry of Education,Department of Hematology Oncology Center,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China)

机构地区：[1]国家儿童医学中心,首都医科大学附属北京儿童医院,北京市儿科研究所,血液疾病研究室,北京100045 [2]国家儿童医学中心,首都医科大学附属北京儿童医院血液肿瘤中心,儿童血液病与肿瘤分子分型北京市重点实验室,儿科重大疾病研究教育部重点实验室,北京100045

出　　处：《中华实用儿科临床杂志》2020年第15期1138-1143,共6页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金(81800189);北京市医院管理中心儿科学科协同发展中心专项经费(XTZD20180202);北京市医院管理中心"青苗"计划专项经费(QML20181205);北京市教育委员会科技发展计划一般项目(KM201910025011)。

摘　　要：目的探讨血浆及全血EB病毒(EBV)DNA水平对EBV相关噬血细胞性淋巴组织细胞增生症(EBV-HLH)患儿预后的影响。方法对2016年1月至2017年12月首都医科大学附属北京儿童医院血液肿瘤中心收治的66例EBV-HLH患儿的临床资料进行回顾性分析,包括入院时、治疗2周、治疗4周血浆及全血EBV-DNA的动态改变,并根据EBV-DNA的拷贝数将血浆EBV-DNA分为阳性组和阴性组,利用受试者工作特征曲线(ROC)将全血EBV-DNA分为高水平组及低水平组;采用χ2检验比较不同水平患儿之间预后不良发生率,Log-Rank检验评估无事件生存情况来分析其预后意义。结果单因素分析结果显示,入院时血浆或全血EBV-DNA水平对EBV-HLH预后影响不大,治疗2周及4周血浆EBV-DNA阳性(≥500拷贝/mL)或全血EBV-DNA载量>(5.04~5.09)×105拷贝/mL是影响患儿预后及无进展生存的重要因素(P<0.001)。此外中枢神经系统受累(P=0.025)、白细胞(WBC)减少(WBC≤3×109/L,P=0.031)、中性粒细胞(ANC)缺乏(ANC≤0.5×109/L,P=0.041)、血红蛋白(Hb)降低(Hb≤90 g/L,P=0.023)及清蛋白减少(≤26 g/L,P=0.012),提示也具有一定预后意义。Cox回归多因素分析显示,仅治疗4周时血浆EBV-DNA载量与中枢神经系统累及是独立预后因素(风险比率=7.139,P=0.032;风险比率=6.455;P=0.042),而不同时间点的全血及治疗2周时血浆EBV-DNA水平的预后价值较低。结论 EVB-HLH患儿治疗4周血浆EBV-DNA水平可作为早期判断病情、尽早识别预后不良的客观指标,能更好地指导EBV-HLH的治疗。Objective To evaluate the prognostic value of Epstein-Barr virus(EBV)-DNA level in plasma and whole blood in treatment of children with EBV-associated hemophagocytic lymphohistiocytosis(EBV-HLH).Methods Clinical data of 66 children with EBV-HLH,who were admitted to the Hematology and Oncology Center of Beijing Children′s Hospital,Capital Medical University from January 2016 to December 2017 were retrospectively reviewed and analyzed.The data included the dynamic changes of the EBV-DNA level in plasma(P-EBV-DNA)and whole blood(W-EBV-DNA)at the time of admission,2 and 4 weeks after treatment.P-EBV-DNA was divided into the positive group and the negative group according to the copy number of EBV-DNA,and W-EBV-DNA was divided into the high and the low level group by the receiver operating characteristic curve(ROC);the incidence of poor prognosis was compared between different groups by Chi-Square test;the event-free survival(EFS)was evaluated by the Log-Rank test to identify its prognostic significance.Results The analysis showed that both P-EBV-DNA and W-EBV-DNA at admission could not be associated with a poor outcome;P-EBV-DNA(≥500 copies/mL)or W-EBV-DNA[>(5.04-5.09)×105 copies/mL]after 2 and 4 weeks of treatment could be a good marker of a poor outcome and progression-free survival(P<0.001).Besides,central nervous system(CNS)involvement(P=0.025),sever leukopenia(WBC≤3×109/L,P=0.031),neutropenia(ANC≤0.5×109/L,P=0.041),albumin reduction(≤26 g/L,P=0.012)and hemoglobin decrease(≤90 g/L,P=0.023)at diagnosis are also associa-ted with worse outcomes.In multivariate analysis,only P-EBV-DNA at 4th week and CNS involvement were indepen-dent prognostic factors(HR=7.139,P=0.032 and HR=6.455,P=0.042,respectively).The prognostic value of W-EBV-DNA at different time points and P-EBV-DNA after 2 weeks of treatment had a lower prognostic value.Conclusions The P-EBV-DNA level after 4 weeks of treatment is a promising risk indicator for early diagnosis of disease and early recognition of poor prognosis in EBV-HLH chil

关 键 词：儿童 EB病毒相关噬血细胞性淋巴组织细胞增生症 EB病毒DNA 预后 

分 类 号：R725.5[医药卫生—儿科]