异基因造血干细胞移植后EBV感染临床危险因素分析

Clinical risks analysis of EBV infection in patients with allogeneic hematopoietic stem cell transplantation

目的 分析异基因造血干细胞移植（allo-HSCT）后EBV感染情况及其危险因素.方法 回顾性分析2012年1月1日至2014年7月31日单中心736例行allo-HSCT患者的临床资料,观察EBV血症、临床诊断的EBV相关疾病（EBV病）及淋巴细胞增殖性疾病（PTLD）发生情况,并分析其危险因素.结果 736例患者中男302例,女434例,中位年龄31（2～62）岁,其中181例患者发生EBV感染,总发生率为24.6％,EBV感染发生的中位时间为57（16～892）d.EBV感染患者中,EBV血症163例（90.0％）,EBV病13例（7.2％）,PTLD 5例（2.8％）.130例患者EBV病毒载量高于1.0＆#215; 104拷贝数/ml,其中67例使用利妥昔单抗抢先治疗,该组患者EBV病及PTLD总发生率显著低于未使用利妥昔单抗抢先治疗患者（6.0％对22.2％,P=0.009）.所有感染EBV患者的总病死率为27.6％,单纯EBV血症病死率为24.5％,EBV病病死率为53.8％,PTLD病死率为60.0％.单因素及多因素分析均提示预处理过程中采用抗胸腺细胞免疫球蛋白（ATG）、HLA不全相合移植、慢性移植物抗宿主病（cGVHD）及CMV感染是allo-HSCT后发生EBV感染的独立危险因素.且EBV初次感染发生时间与采用骨髓或脐血移植（OR=1.156,95％CI1.022～2.250,P=0.039）及cGVHD的发生（OR=0.620,95％ CI 0.453～0.849,P=0.003）密切相关.结论 EBV感染为allo-HSCT后常见并发症,EBV病及PTLD病死率高.EBV感染发生的独立危险因素为处理过程中采用ATG、HLA不全相合移植、cGVHD及CMV感染,采用利妥昔单抗抢先治疗能明显减少EBV相关疾病的发生.

Objective To analyze the prevalence of Epstein Barr Virus （EBV） infection in patients following allogeneic hematopoietic stem cell transplantation （allo-HSCT）.Methods The occurrence of EBV viremia,EBV disease and post-transplant lymphoproliferative disease （PTLD） were retrospectively analyzed in 736 patients received allo-HSCT in single-center from 1 st January 2012 through July 3 l th,2014.Results Of 736 patients （302 male and 434 females） with a median age of 31 （2 to 62） years old,EBV infection occurred in 181 patients,the total incidence of EBV infection was 27.6%,with a median time of 57 （16 to 829） days.The cumulative incidences of probable EBV disease and PTLD were 7.2% （13/181） and 2.8% （5/181）.Viral load higher than 1.0＆#215; 104copies/ml occurs in 130 patients,of which 67 patients received rituximab as pre-empty prophylaxis and significantly reduced the incidences of probable EBV disease and PTLD （6.0% vs 22.2%,P=0.009）.The mortality was 27.6% in all patients with EBV infection：24.5% in EBV viremia,53.8% in probable EBV disease,and 60.6% in PTLD.By univariate and multivariate analysis,the use of anti-thymocyte globulin （ATG）,HLA-mismatch HSCT,cGVHD and CMV reactivation were independent risk factors for EBV infection.The time of first EBV reactivation was closely related with cGVHD（OR=0.620,95% CI 0.453-0.849,P=0.003） and bone marrow or cord blood （OR=1.156,95% CI 1.022-2.250,P=0.039）as source of stem cells for transplantation.Conclusion EBV reactivation is a common complication in patients with allo-HSCT,especially high mortality in PTLD and probable EBV disease.The use of ATG,HLA-mismatch HSCT,cGVHD and CMV reactivation were independent risk factors for EBV infection.The usage of rituximab as pre-empty prophylaxis may reduce the incidences of probable EBV disease and PTLD.