珠蛋白生成障碍性贫血患儿造血干细胞移植术后带状疱疹病毒感染危险因素及预后分析

Risk factors and prognosis of varicella zoster virus infection following hematopoietic stem cell transplantation in children with thalassemia

目的探讨珠蛋白生成障碍性贫血患儿行异基因造血干细胞移植术(allo-HSCT)后感染带状疱疹病毒(VZV)的危险因素及其对患儿预后的影响。方法回顾性收集2012年1月至2020年12月深圳市儿童医院血液肿瘤科造血干细胞移植中心行allo-HSCT的446例珠蛋白生成障碍性贫血患儿的临床资料, 总结发生VZV感染者的临床特征, 根据是否发生VZV进行分组, 组间比较采用χ^(2)检验, 分析其发生的危险因素, 采用Kaplan-Meier法分析2组患儿的预后。结果 446例患儿中19例发生了VZV感染, 发生率为4.3%, 发生的中位时间为移植术后5个月(1.5~11.0个月), 其中5例并发VZV脑炎。患儿予阿昔洛韦加或不加膦甲酸钠抗病毒治疗、输注人免疫球蛋白、局部外涂阿昔洛韦乳膏治疗, 治疗7~28 d(中位治疗时间14 d)疱疹均消退, 合并VZV脑炎者神经系统症状均消失。19例患儿中有1例死亡, 但非VZV感染直接导致死亡, 而是VZV感染后继发植入功能不良, 于VZV感染后5个月发生重症肺炎而死亡。allo-HSCT珠蛋白生成障碍性贫血患儿VZV感染的发生与供者年龄(P=0.010)有关, 与患儿移植时年龄(P=0.378)、性别(P=0.653)、疾病分级(P=0.912)、移植供者类型(P=0.205)、干细胞来源(P=0.624)及急性移植物抗宿主病(P=0.277)均无关。VZV感染对allo-HSCT珠蛋白生成障碍性贫血患儿的预后无显著影响(P=0.241)。结论珠蛋白生成障碍性贫血患儿allo-HSCT术后VZV感染易并发VZV脑炎。脐血移植是高危因素。VZV感染可能不影响allo-HSCT珠蛋白生成障碍性贫血患儿的预后。

Objective To investigate the risk factors and prognosis of varicella zoster virus(VZV)infection in children with thalassemia after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods The clinical data of 446 children with thalassemia who underwent allo-HSCT from January 2012 to December 2020 in the Department of Hematology and Oncology,Shenzhen Children′s Hospital were retrospectively collected.The clinical features of the patients with VZV infection were analyzed.The patients were divided into different groups according to whether they had VZV infection.Categorical variables between groups were compared using the chi-square tests to investigate the risk factors that were associated with the development of VZV.Survival time was analyzed by the Kaplan-Meier method.Results VZV incidence was 4.3%(19/446 cases),and the median onset time was 5 months(1.5-11.0 months)after allo-HSCT.Of the 19 cases with VZV infection,5 cases were complicated with VZV encephalitis.All cases were treated with antiviral agents(Acyclovir alone,or both Acyclovir and Foscarnet),intravenous immunoglobulin and external use of Acyclovir ointment.After 7-28 days of treatment(median treatment time:14 days),all of their herpes subsided,and the neurological symptoms of patients with VZV encephalitis disappeared.One of the 19 children died.The death was not directly caused by VZV infection,but by secondary graft dysfunction and severe pneumonia 5 months after VZV infection.The incidence of VZV infection following allo-HSCT in children with thalassemia was related to the age of the donor(P=0.010),but not to the age of the patient(P=0.378),gender(P=0.653),disease grade of thalassemia(P=0.912),type of the donor(P=0.205),source of stem cells(P=0.624)and acute graft versus host disease(P=0.277).VZV infection had no significant effect on the prognosis of thalassemia children after allo-HSCT(P=0.241).Conclusions Thalassemia children with VZV infection after allo-HSCT are prone to be complicated with VZV encephalitis.Cord blood transplantation is a high risk factor.VZV infection may not have an impact on survival of children with thalassemia after allo-HSCT.