再生障碍性贫血患者亲缘单倍体异基因造血干细胞移植后EB病毒感染危险因素及生存分析

Risk factors and survival of EBV-infected aplastic anemia patients after haploid allogeneic hematopoietic stem cell transplantation

摘要:

目的 分析再生障碍性贫血(AA)患者进行单倍体异基因造血干细胞移植(Haplo-HSCT)后EB病毒(EBV)感染危险因素及患者生存情况。方法 回顾性分析2019年1月1日—2022年10月31日某院血液科78例进行Haplo-HSCT的AA患者临床资料,观察EBV血症、临床诊断的EBV相关性疾病(EBV病)及淋巴细胞增殖性疾病(PTLD)发生情况及出现时间,并分析其危险因素及生存情况。结果 78例患者中男性38例,女性40例,中位年龄33(9~56)岁,其中53例患者发生EBV再激活,总发生率67.9%,发生EBV再激活的中位时间为移植后33(13, 416)d。EBV再激活患者中,单纯EBV血症49例(62.8%),可能的EBV疾病2例(2.6%),已经证实的EBV疾病(PTLD)2例(2.6%)。单因素提示,移植时患者年龄＜40岁、脐血辅助回输、移植后发生急性移植物抗宿主病(aGVHD)、合并巨细胞病毒(CMV)感染是AA患者进行Haplo-HSCT后发生EBV再激活的独立危险因素,多因素分析提示合并CMV感染是AA患者进行Haplo-HSCT后发生EBV再激活的独立危险因素(P=0.048)。干细胞回输前使用利妥昔单抗干预是EBV再激活时间长短的影响因素(P＜0.05)。单纯EBV血症病死率为8.2%,EBV病病死率为50.0%,PTLD病死率为100%。EBV再激活患者2年总生存率为85.3%,EBV未激活患者2年生存率为90.7%,差异无统计学意义(P=0.897),但应用利妥昔单抗治疗的患者其2年生存率低于未使用的患者,差异有统计学意义(P=0.046)。结论 EBV再激活是AA患者进行Haplo-HSCT后常见的严重并发症之一,影响患者的预后和生存。

Abstract:

Objective To analyze the risk factors and survival status of Epstein-Barr virus (EBV) infection in patients with aplastic anemia (AA) after haploid allogeneic hematopoietic stem cell transplantation (Haplo-HSCT). Methods Clinical data of 78 AA patients who underwent Haplo-HSCT in the hematology department of a hospital from January 1, 2019 to October 31, 2022 were analyzed retrospectively. The occurrence and onset time of EBV viremia, EBV-related diseases (EBV diseases), and post-transplant lymphoproliferative disorders (PTLD) were observed, risk factors and survival status were analyzed. Results Among the 78 patients, 38 were males and 40 were females, with a median age of 33 (9-56) years old; 53 patients experienced EBV reactivation, with a total incidence of 67.9%, and the median time for EBV reactivation was 33 (13, 416) days after transplantation. Among patients with EBV reactivation, 49 cases (62.8%) were simple EBV viremia, 2 cases (2.6%) were possible EBV di-seases, and 2 cases (2.6%) were already confirmed EBV diseases (PTLD). Univariate analysis showed that age 1<40 years old at the time of transplantation, umbilical cord blood infusion, occurrence of acute graft-versus-host disease(aGVHD) after transplantation, and concurrent cytomegalovirus (CMV) infection were independent risk factors for EBV reactivation in AA patients after Haplo-HSCT. Multivariate analysis showed that concurrent CMV infection was an independent risk factor for EBV reactivation in AA patients after Haplo-HSCT (P=0.048). Ritu-ximab intervention before stem cell reinfusion was a factor affecting the duration of EBV reactivation (P<0.05). The mortality of EBV viremia, EBV diseases, and PTLD alone were 8.2%, 50.0%, and 100%, respectively. The 2-year overall survival rate of patients with and without EBV reactivation were 85.3%, and 90.7%, respectively, difference was not statistically significant (P=0.897). However, patients treated with rituximab had 2-year lower survival rate than those who did not use it, with a statistically significant difference (P=0.046). Conclusion EBV reactivation is one of the serious complications in AA patients after Haplo-HSCT, which affects the prognosis and survival of patients.