造血干细胞移植治疗Wiskott-Aldrich综合征60例分析

Therapeutic efficacy of hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome in 60 children

目的:评估造血干细胞移植(HSCT)对于Wiskott-Aldrich综合征(WAS)的治疗效果,并探讨影响预后的相关因素。方法:回顾性分析2006年1月至2020年12月在上海儿童医学中心接受HSCT的60例WAS患儿的临床资料。所有患儿均采用以白消安加环磷酰胺的清髓预处理方案,以环孢素加抗人胸腺球蛋白为主的移植物抗宿主病(GVHD)预防方案。观察患儿移植后植入情况、GVHD情况、移植相关并发症、免疫重建及生存情况。采用Kaplan-Meier法进行生存分析并绘制生存曲线,Log-Rank法进行单因素比较。结果:入组60例患儿均为男性,以感染和出血为主要临床特征,确诊时年龄为0.4(0.3,0.8)岁,移植年龄为1.1(0.6,2.1)岁。20例为人类白细胞抗原(HLA)全相合移植,40例为非全相合移植。有35例接受外周血HSCT,25例为脐血移植。所有病例均完全植入。急性GVHD共29例(48%),仅2例(7%)发生Ⅲ度急性GVHD,慢性GVHD发生率为23%(13/56),均为局限性。巨细胞病毒(CMV)和EB病毒血症分别为21例(35%)及20例(33%),7例发生CMV视网膜炎,3例失明。有5例(8%)患儿发生肝窦阻塞综合征,2例死亡。共有7例(12%)移植后自身免疫性血细胞减少。移植后自然杀伤细胞最早重建,B细胞、CD4^(+)T细胞均在移植后180 d左右恢复正常。本组患儿5年总生存率为93%(95%CI 86%~99%),无事件生存率为87%(95%CI 78%~95%)。无CMV复燃组无事件生存率高于有CMV复燃组[95%(37/39)比71%(15/21),χ^(2)=5.22,P=0.022]。结论:HSCT治疗WAS总体预后良好,尽早对典型患儿实施HSCT可以获得更好的疗效,移植后CMV感染是影响生存的主要因素,加强并发症管理能提高患儿生存情况。

Objective To evaluate the therapeutic efficacy of hematopoietic stem cell transplantation(HSCT)for Wiskott-Aldrich syndrome(WAS),and to analyze the factors related to the outcomes.Methods The clinical data of 60 children with WAS received HSCT in Shanghai Children′s Medical Center from January 2006 to December 2020 were retrospectively analyzed.All cases were treated with a myeloablative conditioning regimen with busulfan and cyclophosphamide,and a graft-versus-host disease(GVHD)prevention regimen based on cyclosporine and methotrexate.Implantation,GVHD,transplant-related complications,immune reconstitution and survival rate were observed.Survival analysis was performed by Kaplan-Meier method,and Log-Rank method was used for univariate comparison.Results The 60 male patients had main clinical features as infection and bleeding.The age at diagnosis was 0.4(0.3,0.8)years,and the age at transplantation was 1.1(0.6,2.1)years.There were 20 cases of human leukocyte antigen matched transplantation and 40 mismatched transplantation;35 patients received peripheral blood HSCT,and 25 cord blood HSCT.All cases were fully implanted.The incidence of acute GVHD(aGVHD)was 48%(29/60)and only 2(7%)developed aGVHD of gradeⅢ;the incidence of chronic GVHD(cGVHD)was 23%(13/56),and all cases were limited.The incidence of CMV and EBV infection was 35%(21/60)and 33%(20/60)respectively;and 7 patients developed CMV retinitis.The incidence of sinus obstruction syndrome was 8%(5/60),of whom 2 patients died.There were 7 cases(12%)of autoimmune hemocytopenia after transplantation.Natural killer cells were the earliest to recover after transplantation,and B cells and CD4^(+)T cells returned to normal at about 180 days post HSCT.The 5-year overall survival rate(OS)of this group was 93%(95%CI 86%-99%),and the event free survial rate(EFS)was 87%(95%CI 78%-95%).EFS of non-CMV reactivation group is higher than that of CMV reactivation group(95%(37/39)vs.71%(15/21),χ^(2)=5.22,P=0.022).Conclusions The therapeutic efficacy of HSCT for WAS is satisfying,and the early application of HSCT in typical cases can achieve better outcome.CMV infection is the main factor affecting disease-free survival rate,which can be improved by strengthening the management of complications.