Abstract:

Objective    To explore the main causes of deceased cases and factors related with Epstein-Barr virus associated hemophagocytic lymphohistiocytosis（EBV-HLH） fatality. Methods    A retrospective study was performed on EBV-HLH cases admitted to Beijing Children’s Hospital between June 2003 and October 2010. All patients’ medical records were reviewed and analyzed. Follow-up was taken to get the prognosis information of all cases. Statistical evaluation was conducted using multivariate and univariate analysis. Results    In the 90 cases of follow-up results， 32 were alive while another 58 were deceased and the overall fatality rate was 64.4%. Most patients （33/36） without undergoing chemotherapy died in short time after diagnosis of HLH （usually less than two months）. The fatality rate was as high as 87.8% in non-chemotherapy group while it was 44.9% in chemotherapy group. Despite being given chemotherapy， 8 patients died within 2 months of diagnosis while 14 cases died 2 months after diagnosis. Seven of 8 patients suffered from severe infection， while 6 cases had severe coagulopathy and 7 cases had multiple organ failure. Causes of late deaths mainly included non-remission of the disease after chemotherapy （9 in 14） and relapse of HLH （4 in 14）. The fibrinogen was lower in deceased group than in survived group， while lactate dehydrogenase was higher. Logistic regression analysis showed that longer than 4 weeks of illness prior to diagnosis （OR=3.436）， non-chemotherapy （OR=11.09） and lower fibrinogen level （OR=1.866） were independent factors related with EBV-HLH fatality. Conclusion    EBV-HLH is a severe disease in pediatric patients with poor outcome and high fatality rate. Severe infection， coagulopathy and multiple organ failure are the main reasons which cause the early deaths， while non-remission of the disease after chemotherapy or relapse of HLH cause deaths after two months of diagnosis. Longer than 4 weeks of illness prior to diagnosis， non-chemotherapy and lower fibrinogen level are factors related to EBV-HLH fatality.

Key words: Epstein-Barr virus, hemophagocytic lymphohistiocytosis, fatality, risk factors

摘要：

目的    探讨儿童EB病毒感染相关噬血细胞淋巴组织细胞增生症（Epstein-Barr virus associated hemophagocytic lymphohistiocytosis， EBV-HLH）的主要死因及相关危险因素。方法    回顾性分析首都医科大学附属北京儿童医院2003年6月至2010年10月收治的103例EBV-HLH 患儿临床资料，并对其转归进行随访。采用单因素及多因素分析方法进行统计学分析。结果    本组失访13例。随访成功的90例患儿中，存活32例，死亡58例，病死率为64.4%。其中未进行化疗的36例患儿病死率高达87.8%，其中33例在诊断后2个月内死亡；接受化疗患儿（化疗组）的病死率为44.9%。化疗组8例诊断后早期死亡病例，其中7例发生重症感染；6例发生严重的凝血功能障碍；7例发生脏器功能衰竭。14例晚期死亡病例中，9例患儿在化疗后病情持续不缓解并最终死亡；4例在停药后出现复发而死亡。单因素分析显示死亡组较存活组患儿的纤维蛋白原水平更低，而乳酸脱氢酶更高（P1 = 0.033、P2 = 0.005，均< 0.05）； Logistics回归分析显示，发病-诊断时间大于4周、未进行化疗及低纤维蛋白原均为与EBV-HLH患儿死亡相关的危险因素，其死亡危险度分别为3.436、11.09和1.866。结论    儿童EBV-HLH预后差、病死率高。重症感染、凝血功能障碍及脏器功能衰竭是早期死亡主要原因；持续疾病活动及复发为晚期死亡的主要原因。发病-诊断时间大于4周、未进行化疗及低纤维蛋白原水平为与EBV-HLH死亡相关的危险因素。

关键词: Epstein-Barr病毒, 噬血细胞淋巴组织细胞增生症, 死亡, 危险因素