Human Herpesvirus 6 (HHV-6) Reactivation and HHV-6 Encephalitis After Allogeneic Hematopoietic Cell Transplantation: A Multicenter, Prospective Study
Human Herpesvirus 6 (HHV-6) Reactivation and HHV-6 Encephalitis After Allogeneic Hematopoietic Cell Transplantation: A Multicenter, Prospective Study
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DOI：
10.1093/cid/cit358
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发表时间：
2013-09-01
影响因子：
11.8
通讯作者：
Fukuda, Takahiro
中科院分区：
文献类型：
--
作者：
Ogata, Masao;Satou, Takako;Fukuda, Takahiro
背景。同种异体造血细胞移植（HCT）后人类疱疹病毒6型（HHV-6）脑炎的流行病学及其与HHV-6再激活的关系尚未得到充分的描述。这项前瞻性、多中心研究调查了230名异体HCT受者的HHV-6再激活和HHV-6脑炎的流行病学。在hct后70天，每周两次前瞻性评估血浆HHV-6 DNA载量。HCT后第70天，HHV-6 DNA阳性和高水平HHV-6再激活（血浆HHV-6 DNA >= 10(4)拷贝/mL）的累积发生率分别为72.2%和37.0%。多因素分析发现，清骨髓调节（危险比[HR]， 1.9; P = 0.004）、脐带血移植（HR, 2.0; P = 0.003）和男性（HR, 1.6; P = 0.04）是显示HHV-6高水平再激活的危险因素。7例患者发生HHV-6脑炎，第70天累计发病率为3.0%。144例无高水平HHV-6再激活的患者中无一例发生HHV-6脑炎，86例高水平HHV-6再激活的患者中有7例（8.1%）发生HHV-6脑炎（P = 0.0009）。接受UCBT的患者的HHV-6脑炎患病率明显高于其他来源的患者（第70天累积发病率，7.9% vs 1.2%, P = 0.008）。在7例HHV-6脑炎患者中，中枢神经系统（CNS）症状均伴有血浆HHV-6 DNA峰值（范围：21 656 ~ 433 639拷贝/mL）。高水平的血浆HHV-6 DNA与HHV-6脑炎的高风险相关。UCBT是HHV-6脑炎的重要危险因素。异体HCT后，如果伴有高水平血浆HHV-6 DNA，则应考虑HHV-6脑炎。
Background. The epidemiology of human herpesvirus 6 (HHV-6) encephalitis after allogeneic hematopoietic cell transplantation (HCT) and its relationship with HHV-6 reactivation have not been sufficiently characterized.Methods. This prospective, multicenter study of 230 allogeneic HCT recipients investigated the epidemiology of HHV-6 reactivation and HHV-6 encephalitis. Plasma HHV-6 DNA load was prospectively evaluated twice weekly until 70 days after HCT.Results. Cumulative incidence of positive HHV-6 DNA and high-level HHV-6 reactivation (plasma HHV-6 DNA >= 10(4) copies/mL) at day 70 after HCT was 72.2% and 37.0%, respectively. Multivariate analysis identified myeloablative conditioning (hazard ratio [HR], 1.9; P = .004), umbilical cord blood transplantation (UCBT) (HR, 2.0; P = .003), and male sex (HR, 1.6; P = .04) as risk factors for displaying high-level HHV-6 reactivation. HHV-6 encephalitis occurred in 7 patients, and cumulative incidence at day 70 was 3.0%. None of the 144 patients without high-level HHV-6 reactivation and 7 of 86 patients (8.1%) with high-level HHV-6 reactivation developed HHV-6 encephalitis (P = .0009). Prevalence of HHV-6 encephalitis was significantly higher among patients receiving UCBT than in patients with other sources (cumulative incidence at day 70, 7.9% vs 1.2%, P = .008). In each of 7 patients with HHV-6 encephalitis, central nervous system (CNS) symptoms developed concomitant with peak plasma HHV-6 DNA (range, 21 656-433 639 copies/mL).Conclusions. High levels of plasma HHV-6 DNA are associated with higher risk of HHV-6 encephalitis. UCBT is a significant risk factor for HHV-6 encephalitis. HHV-6 encephalitis should be considered if CNS dysfunction develops concomitant to high-level plasma HHV-6 DNA after allogeneic HCT.