title: Human herpesvirus 6 (HHV-6) reactivation and HHV-6 encephalitis after allogeneic hematopoietic cell transplantation: a multicenter, prospective study.
abstract: 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 the144 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.
authors.affiliation: Department of Hematology, Oita University Hospital, Hasama-machi, Yufu-city 879-5593, Japan. mogata@oita-u.ac.jp
authors.forename: Masao
authors.initials: M
authors.lastname: Ogata
authors.forename: Takako
authors.initials: T
authors.lastname: Satou
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kadota
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Saito
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okumura
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Ueki
authors.forename: Koji
authors.initials: K
authors.lastname: Nagafuji
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kako
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Uoshima
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Tsudo
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Itamura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects*; D004279:DNA, Viral / Q000097:blood; D018792:Encephalitis, Viral / Q000453:epidemiology* / Q000821:virology; D005260:Female; D015654:Herpesvirus 6, Human / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019349:Roseolovirus Infections / Q000453:epidemiology* / Q000821:virology; D019562:Viral Load; D014775:Virus Activation; D055815:Young Adult
chemical_list: D004279:DNA, Viral
keywords: HHV-6 encephalitis; HHV-6 reactivation; allogeneic hematopoietic cell transplantation; human herpesvirus 6; viral load