中枢神经系统EBV感染对EBV相关噬血细胞综合征患者预后的影响

Effect of EBV infection in central nervous system on prognosis of patients with EBV-associated hemophagocytic lymphohistiocytosis

目的:探讨中枢神经系统EB病毒(EBV)感染对EBV相关噬血细胞综合征(EBV-HLH)患者预后的影响。方法:回顾性分析2017年1月1日—2019年9月1日我院血液科诊治的88例EBV-HLH患者的临床资料,该88例患者全部完善腰椎穿刺及脑脊液EBV-DNA检测。临床资料包括患者性别、年龄、脑脊液EBVDNA拷贝数、脑脊液白细胞、潘氏试验、脑脊液总蛋白、脑脊液葡萄糖,是否行异基因造血干细胞移植(allo-HSCT)、预后、生存时间等。结果:EBV^(+)患者(44例)的脑脊液白细胞、潘氏试验、脑脊液总蛋白、脑脊液葡萄糖指标与EBV^(-)患者(44例)比较,差异均无统计学意义;EBV^(+)患者的生存时间明显差于EBV-患者(7.3个月vs 8.2个月,P=0.049)。行allo-HSCT患者(60例)的生存时间明显优于未行allo-HSCT患者(28例)(9.8个月vs 4.7个月,P=0.040)。在44例脑脊液EBV-DNA阳性患者中,行allo-HSCT患者(32例)的生存时间明显优于未行allo-HSCT患者(12例)(19.6个月vs 4.3个月,P<0.001)。此44例患者脑脊液最高EBV-DNA拷贝数的中位数为1.0×10^(4)拷贝/mL,以1.0×10^(4)拷贝/mL为界,脑脊液EBV-DNA拷贝数高的患者(17例)生存时间明显差于脑脊液EBV-DNA拷贝数低的患者(27例)(5.2个月vs 17.0个月,P=0.030)。在31例多次进行脑脊液EBV-DNA检测的患者中,27例患者首次脑脊液EBV-DNA阳性。将此27例患者根据脑脊液EBV-DNA是否由阳性转为阴性分组,脑脊液EBV-DNA阳性转为阴性患者(16例)的生存时间明显优于脑脊液EBV-DNA持续阳性患者(11例)(9.4个月vs 5.0个月,P=0.038)。结论:在EBV-HLH患者中,中枢神经系统EBV感染是一个不良预后因素。脑脊液EBV-DNA拷贝数及变化趋势对EBV-HLH患者的预后存在影响,监测脑脊液EBVDNA拷贝数变化具有重要意义。对于脑脊液EBV-DNA阳性的EBV-HLH患者,allo-HSCT可以改善其预后。

Objective:To explore the effect of EBV infection in central nervous system on the prognosis of patients with EBV^(-)associated hemophagocytic lymphohistiocytosis(EBV-HLH).Methods:Clinical data of 88patients with EBV-HLH diagnosed and treated in our hospital from January 1,2017to September 1,2019were retrospectively analyzed.All 88patients completed lumbar puncture and cerebrospinal fluid EBV-DNA detection.Clinical data included patients'gender,age,copy number of EBV-DNA in cerebrospinal fluid,cerebrospinal fluid leukocytes,pan test,cerebrospinal fluid total protein and glucose in routine biochemical examination of cerebrospinal fluid,whether allogeneic hematopoietic stem cell transplantation(allo-HSCT)was performed,prognosis,survival time and so on.Results:There was no significant difference in cerebrospinal fluid leukocytes,pan test,cerebrospinal fluid total protein and glucose between EBV^(+)patients(44cases)and EBV-patients(44cases),and the survival time in EBV^(+)patients was significantly worse than that in EBV-patients(7.3months vs 8.2months,P=0.049).The survival time in patients underwent allo-HSCT(60cases)was significantly better than that in patients without allo-HSCT(28cases)(9.8months vs 4.7months,P=0.040).Among the 44patients with EBV-DNA positive in cerebrospinal fluid,the survival time in patients underwent allo-HSCT(32cases)was significantly better than that in patients without allo-HSCT(12cases)(19.6months vs 4.3months,P<0.001).The median of the highest EBV-DNA copy number in cerebrospinal fluid was 1.0×10^(4)copies/mL,taking 1.0×10^(4)copies/mL as the boundary,the survival time of patients with high EBV-DNA copy number in cerebrospinal fluid(17cases)was significantly worse than that of patients with low EBV-DNA copy number in cerebrospinal fluid(27cases)(5.2months vs 17.0months,P=0.030).Among 31patients who underwent cerebrospinal fluid EBV-DNA detection for many times,27cases were positive for EBV-DNA in cerebrospinal fluid for the first time.And they were divided into 2groups according to whether the cerebrospinal fluid EBV-DNA detection changed from positive to negative.The survival time of patients in the cerebrospinal fluid EBV-DNA changed from positive to negative group(16cases)was significantly better than that in the cerebrospinal fluid EBV-DNA continuous positive group(11cases)(9.4months vs 5.0months,P=0.038).Conclusion:EBV infection of the central nervous system is a poor prognostic factor in patients with EBV-HLH.The EBV-DNA copy number and changes in EBV-DNA in cerebrospinal fluid can affect the prognosis of patients with EBV-HLH.It is of great significance to monitor the changes in EBV-DNA copy number in the cerebrospinal fluid.Allo-HSCT can improve the prognosis of EBV-HLH patients with EBV-DNA positive in cerebrospinal fluid.