1 027例儿童异基因造血干细胞移植后EB病毒感染的临床特征及其影响因素

Clinical characteristics of EB virus infection in 1 027 children undergoing allogeneic hematopoietic stem cell transplantation and influencing factors

  • 摘要:
    目的 总结儿童异基因造血干细胞移植(allo-HSCT)后EB病毒(EBV)感染的临床特征、危险因素及在利妥昔单抗抢先治疗背景下EBV感染对预后的影响。
    方法 回顾性分析深圳市儿童医院2019年1月-2023年12月allo-HSCT患者的临床资料,观察EBV血症及EBV相关移植后淋巴增殖性疾病(EBV-PTLD)发生情况,分析其危险因素及预后。
    结果 1 027例患者中有244例(23.76%)发生EBV血症,中位发病时间为移植后86.00(61.00~221.00)d,44例(4.28%)发生EBV-PTLD,中位发病时间为移植后77.00(55.50~140.50)d。多因素logistic回归分析显示移植前半年内使用利妥昔单抗是allo-HSCT后发生EBV血症的保护因素,而危险因素包括原发病为骨髓衰竭性疾病、供者EBV核心抗原抗体阳性和使用抗胸腺细胞球蛋白(ATG)。未使用ATG、ATG剂量在0~10 mg/kg及ATG剂量≥10 mg/kg的EBV血症1年累积发生率分别为10.00%、26.88%及50.00%(P<0.001)。EBV-PTLD的高危因素有受者为女性、移植后出现EBV血症、ATG剂量≥10 mg/kg,而移植前半年内使用利妥昔单抗并非EBV-PTLD的保护因素(P=0.117)。EBV血症和EBV-PTLD患者的总生存率分别为(97.50±0.010)%、(97.70±0.022)%,与未发生者之间无明显差异(P=0.634,P=0.899)。
    结论 EBV感染是儿童allo-HSCT后常见并发症,移植前半年内使用利妥昔单抗可减少EBV血症的发生,ATG剂量≥10 mg/kg是EBV血症和EBV-PTLD共同的高危因素,在利妥昔单抗抢先治疗的背景下EBV血症及EBV-PTLD可能并未显著影响患者的生存和预后。

     

    Abstract:
    OBJECTIVE To summarize the clinical characteristics, risk factors of Epstein-Barr virus (EBV) infection in children undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), and the impact of EBV infection on prognosis under the context of preemptive treatment with rituximab.
    METHODS A retrospective analysis was conducted on the clinical data of patients who underwent allo-HSCT at Shenzhen Children′s Hospital from Jan. 2019 to Dec. 2023. The occurrence of EBV viremia and EBV-associated post-transplant lymphoproliferative disease (EBV-PTLD) was observed, and their risk factors and prognosis were analyzed.
    RESULTS Among the 1 027 patients, 244 (23.76%) developed EBV viremia, with a median onset time of 86.00 (61.00~221.00) days after transplantation, while 44 patients (4.28%) developed EBV-PTLD, with a median onset time of 77.00 (55.50~140.50) days after transplantation. Multivariate logistic regression analysis revealed that the use of rituximab within six months prior to transplantation was a protective factor against EBV viremia after allo-HSCT, while risk factors included primary diseases being bone marrow failure disorders, donor EBV core antigen antibody and the use of anti-thymocyte globulin (ATG). The cumulative incidence rates of EBV viremia in 1 year were 10.00%, 26.88% and 50.00% for patients who did not receive ATG, received ATG at a dose of 0-10 mg/kg, and received ATG at a dose ≥10 mg/kg, respectively (P < 0.001). High-risk factors for EBV-PTLD included female recipients, the occurrence of EBV viremia after transplantation and ATG dosage ≥10 mg/kg, while the use of rituximab within six months prior to transplantation was not a protective factor against EBV-PTLD (P=0.117). The overall survival rates of patients with EBV viremia and EBV-PTLD were (97.50±0.010)% and (97.70±0.022)%, respectively, with no significant difference compared to those without these conditions (P=0.634, P=0.899).
    CONCLUSIONS EBV infection is a common complication in children after allo-HSCT. The use of rituximab within six months prior to transplantation can reduce the occurrence of EBV viremia. An ATG dosage ≥10 mg/kg is a common high-risk factor for both EBV viremia and EBV-PTLD. Under the context of preemptive treatment with rituximab, EB nirus viremia and EBV-PTLD may not significantly affect patient survival and prognosis.

     

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