Department of Oncology, Hematology and Stem Cell Transplantation, University Children's Hospital Würzburg, Würzburg, Germany.
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
PLoS One. 2020 Feb 4;15(2):e0228451. doi: 10.1371/journal.pone.0228451. eCollection 2020.
Viral reactivation occurs frequently in the context of immunodeficiency and immunosuppression after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and can cause severe complications. The aim of this single-center retrospective analysis was to characterize viral infections in the first year after HSCT, to investigate risk factors and to study the impact of viral infections on transplantation outcome. This will facilitate the identification of at-risk patients and the development of new preventive strategies. 107 pediatric allo-HSCT from January 2005 through December 2015 were analyzed for infections with Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), adenovirus (ADV), herpes simplex virus (HSV) and varicella zoster virus (VZV). Viral infections were detected after 68.2% of transplantations. The viruses most commonly encountered were HHV-6 (36/107) and EBV (30/107). Severe viral disease was rare (7/107) and none of the patients died as result of viral reactivation. Important risk factors for viral infections were higher age at HSCT, donor type and occurrence of acute graft-versus-host disease (aGvHD). Especially for EBV, transplant from an unrelated donor and in-vivo T-cell depletion (TCD) had a significant effect on infection rates, whereas for CMV the strongest effect was seen by donor and recipient serostatus with recipient seropositivity most predictive for reactivation. The occurrence of severe aGvHD was associated with EBV and ADV infections. For HSV, the recipient serostatus was identified as prognostic factor for HSV infections, while we found higher age at time of HSCT as risk factor for VZV infections. The overall survival of patients with or without viral infections did not differ significantly. Interestingly, when looking at the 85 patients in our cohort who had received an HSCT for a malignant disease, a tendency towards lower relapse rates was seen in patients affected by viral infections (HR 0.51, 95% CI 0.25 - 1.06, p = 0.072). Viral reactivations are common after pediatric allo-HSCT, though severe complications were rare in our collective. Determining risk factors for viral reactivations may help to identify patients in need of intensified monitoring and to individualize preventive strategies.
病毒再激活在异基因造血干细胞移植（allo-HSCT）后免疫缺陷和免疫抑制的情况下经常发生，并可导致严重并发症。本单中心回顾性分析的目的是描述 HSCT 后 1 年内的病毒感染情况，探讨危险因素，并研究病毒感染对移植结果的影响。这将有助于识别高危患者并制定新的预防策略。
分析了 2005 年 1 月至 2015 年 12 月期间 107 例儿科 allo-HSCT 患者的 EBV、CMV、HHV-6、ADV、HSV 和 VZV 感染情况。在 68.2%的移植后检测到病毒感染。最常见的病毒是 HHV-6（36/107）和 EBV（30/107）。严重的病毒性疾病很少见（7/107），没有患者因病毒再激活而死亡。病毒感染的重要危险因素是 HSCT 时年龄较大、供体类型和急性移植物抗宿主病（aGvHD）的发生。特别是对于 EBV，来自无关供体和体内 T 细胞耗竭（TCD）对感染率有显著影响，而对于 CMV，供体和受体的血清状态影响最大，受体血清阳性预测再激活的可能性最大。严重 aGvHD 的发生与 EBV 和 ADV 感染有关。对于 HSV，受体的血清状态被确定为 HSV 感染的预后因素，而我们发现 HSCT 时年龄较大是 VZV 感染的危险因素。有或没有病毒感染的患者的总生存率没有显著差异。有趣的是，当我们观察我们队列中 85 例接受恶性疾病 HSCT 的患者时，发现病毒感染患者的复发率较低（HR 0.51，95%CI 0.25-1.06，p=0.072）。病毒再激活在儿科 allo-HSCT 后很常见，但在我们的研究中严重并发症很少见。确定病毒再激活的危险因素可能有助于识别需要强化监测的患者，并制定个体化的预防策略。
