HERPESVIRUS INFECTIONS REACTIVATION IN ONCOLOGICAL PEDIATRIC PATIENTS

S. Lapaeva, Y. Toshina, Y. Dinikina
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Abstract

Herpesvirus infection (HVI) reactivation in children with cancer is a common complication during the period of postcytostatic immunosuppression and occurs mostly after courses of high-dose chemotherapy (HDCT) with hematopoietic stem cell transplantation (HSCT). Clinical manifestations can range from asymptomatic viral reactivation and chemo-induced cytopenia worsening to fatal outcomes of the disease coupled with multiorgan involvement. The purpose of the research was to analyze cases of HVI reactivation in oncological pediatric patients in order to identify the risk factors for HVI development, features of its clinical manifestations and the effectiveness of antiviral therapy. Materials and methods used: a single-center retrospective cohort study was provided. The register of HVI reactivation cases in patients receiving antitumor therapy at the V.A. Almazov National Medical Research Centre of the Ministry of Healthcare of Russia (Saint Petersburg, Russia) in Jan. 2017-Jul. 2021 was analyzed. Routine monitoring of HVI reactivation (CMV, HHV-6A/B, EBV) included determination of viral DNA in patients’ biological materials by PCR using the AmpliSens test system on a Rotor-Gene device (amplifier). Results: 40 cases of HVI reactivation were registered, 22 (55%) were associated with cytomegalovirus infection (CMV), 4 (10%) with human herpes virus 6 (HHV-6A/B), 3 (7.5%) with Epstein-Barr virus (EBV) and 11 (27.5%) mixed. DNAemia was registered in 55%, organ damage in 45%. More often, reactivation of HVI developed after allogeneic HSCT (alloHSCT) (42,5%), autologous HSCT (autoHSCT) (40%). A statistically significant decrease of HVI reactivation cases was observed in patients after alloHSCT without TCRaβ depletion (53% v. 5,5%, p=0.036). Antiviral therapy was carried out in all patients. The first-line drug most often was ganciclovir (60%). Second line antiviral therapy was required in 10% of cases and those were the only CMV infection cases. Conclusion: a statistically significant decrease of HVI reactivation cases was observed in patients without TCRaβ depletion in alloHSCT. The clinical signs usually are not specific and require routine laboratory monitoring. Adequate antiviral therapy allowed achieving infectious control over HVI in most of the cases.
儿科肿瘤患者的疱疹病毒感染再活化
癌症患儿的疱疹病毒感染(HVI)再活化是细胞抑制后免疫抑制期的常见并发症,主要发生在造血干细胞移植(HSCT)的高剂量化疗(HDCT)疗程之后。临床表现从无症状的病毒再激活、化疗引起的全血细胞减少恶化到多器官受累的致命后果。本研究的目的是分析肿瘤儿科患者的 HVI 再激活病例,以确定 HVI 发生的风险因素、临床表现特征和抗病毒治疗的有效性。所用材料和方法:这是一项单中心回顾性队列研究。该研究分析了俄罗斯医疗保健部 V.A. Almazov 国家医学研究中心(俄罗斯圣彼得堡)2017 年 1 月至 2021 年 7 月接受抗肿瘤治疗患者的 HVI 再激活病例登记。对HVI再活化(CMV、HHV-6A/B、EBV)的常规监测包括使用Rotor-Gene设备(放大器)上的AmpliSens检测系统,通过PCR法测定患者生物材料中的病毒DNA。结果登记的 40 例 HVI 再激活病例中,22 例(55%)与巨细胞病毒感染(CMV)有关,4 例(10%)与人类疱疹病毒 6(HHV-6A/B)有关,3 例(7.5%)与爱泼斯坦-巴尔病毒(EBV)有关,11 例(27.5%)为混合感染。55%的患者出现DNA血症,45%的患者出现器官损伤。异基因造血干细胞移植(alloHSCT)(42.5%)和自体造血干细胞移植(autoHSCT)(40%)后出现 HVI 再激活的比例更高。在未进行TCRaβ清除的异基因造血干细胞移植后,HVI再激活病例明显减少(53% 对 5.5%,P=0.036)。所有患者都接受了抗病毒治疗。最常见的一线药物是更昔洛韦(60%)。10%的病例需要进行二线抗病毒治疗,这些是唯一的 CMV 感染病例。结论:在异体母细胞移植中未发现TCRaβ耗竭的患者中,HVI再激活病例在统计学上显著减少。临床症状通常不具有特异性,需要进行常规实验室监测。适当的抗病毒治疗可使大多数病例的 HVI 感染得到控制。
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