Human Herpesvirus 6 (HHV-6) Reactivation and HHV-6 Encephalitis After Allogeneic Hematopoietic Cell Transplantation: A Multicenter, Prospective Study

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.