异基因造血干细胞移植术后患儿带状疱疹病毒感染的临床研究

Clinical study on varicella zoster virus infection in children following allogeneic hematopoietic stem cell transplantation

目的探讨异基因造血干细胞移植(allo-HSCT)后患儿带状疱疹病毒(VZV)感染的危险因素,为儿童接受allo-HSCT后并VZV感染的诊断、监测、预防及治疗提供参考。方法收集2012年1月至2015年6月在南方医科大学南方医院儿科造血干细胞移植中心367例接受allo-HSCT的患儿临床资料,回顾性分析接受allo-HSCT后合并VZV感染患儿的临床特征,并分析其危险因素。结果367例行allo-HSCT的患儿中有34例并VZV感染,发病率为9.26%,发病中位时间96.5 d(19~326 d),其中2例复发3次,1例复发2次,3例复发1次,另有4例并VZV脑炎。患儿予阿昔洛韦抗病毒治疗、输注人免疫球蛋白、调整免疫抑制剂用量及局部应用阿昔洛韦软膏,中位治疗时间13 d(7~28 d),疱疹均消退,头痛、呕吐、抽搐等神经系统症状消失。无一例因VZV感染直接导致死亡。allo-HSCT后VZV感染的发生与年龄(χ^2=6.863,P=0.009)、基础疾病(χ^2=14.793,P=0.022)、移植方式(χ^2=14.459,P=0.001)及干细胞来源(χ^2=20.585,P=0.002)有关,与性别(χ^2=0.106,P=0.745)、预处理方案是否含抗胸腺细胞球蛋白(χ^2=0.010,P=0.921)无关。结论VZV感染主要发生在allo-HSCT后12个月内,易并VZV脑炎,阿昔洛韦治疗效果好。对于存在高危因素的患儿应加强移植后VZV的监测及预防治疗。

Objective To analyze the risk factors of varicella zoster virus(VZV) infection after allogeneic hematopoietic stem cell transplantation(allo-HSCT) in children, and to provide reference for the diagnosis, monitoring and prophylaxis of VZV infection after allo-HSCT. Methods A total of 367 patients, who underwent allo-HSCT in Pediatric Transplantation Center of Nanfang Hospital Affiliated to Southern Medical University from January 2012 to June 2015 were collected.Clinical characteristics and risk factors of the patients complicated with VZV after allo-HSCT were retrospectively analyzed. Results Thirty-four patients (9.26%) were complicated with VZV infection after allo-HSCT.The median onset time was 96.5 d(19-326 d). Two of 34 patients relapsed 3 times, 1 case of them relapsed twice, 3 cases of them relapsed once, and 4 cases of 34 patients were complicated with VZV encephalitis.All cases were treated with antivirus drugs, infusion of immunoglobulin, reduction of immunosuppressant dosages, with external use of Acyclovir ointment.The median therapy time was 13 days (7-28 days). All of their herpes subsided, and neurological symptoms such as headache, vomiting and convulsion disappeared.VZV-DNA both in blood and cerebrospinal fluid turned negative.No patient had herpetic dissemination and visceral involvement, and no one died directly of VZV infection.Results indicated that age(χ^2=6.863, P=0.009), underlying disease(χ^2=14.793, P=0.022), type of HSCT(χ^2=14.459, P=0.001) and resource of stem cell (χ^2=20.585, P=0.002) were significant risk factors for VZV infection after allo-HSCT, while sex (χ^2=0.106, P=0.745) and antithymocyte globulin in conditioning regimen(χ^2=0.010, P=0.921) had no relation to it. Conclusions VZV infection mainly occur within 12 months after allo-HSCT and is prone to be complicated with VZV encephalitis.The effect of Acyclovir is good.Monitoring and prophylaxis of VZV infection after allo-HSCT should be strengthened in children with high risk factors.