title: Reactivation of Human Herpes Virus-6 After Pediatric Stem Cell Transplantation: Risk Factors, Onset, Clinical Symptoms and Association With Severity of Acute Graft-Versus-Host Disease.
abstract: METHODS
  To study clinical symptoms, timing and consequences of human herpesvirus-6 (HHV-6) reactivation after pediatric allogeneic stem cell transplantation (SCT), HHV-6 was investigated by plasma polymerase chain reaction in a cohort of 106 pediatric SCT recipients.
  
  
  RESULTS
  HHV-6 viremia was detected post-SCT in 48% of the patients with a median time of onset at 20 days after SCT. In week 3 and 4 post-SCT, HHV-6 is the most common infectious agent detected. In up to 30% of the patients with fever of unknown origin, HHV-6 was the only detected infectious agent to explain fever. Patients transplanted with an unrelated donor or receiving serotherapy were at increased risk of HHV-6 reactivation. The onset of HHV-6 reactivation coincided with the appearance of lymphocytes and monocytes in peripheral blood. Treatment with alemtuzumab (MabCampath) delayed both lymphocyte and monocyte engraftment and, concomitantly, onset of HHV-6 reactivation was delayed in those cases. HHV-6 reactivation was not associated with an increased incidence of acute graft-versus-host disease (GvHD). However, progression to grade II-IV GvHD was in 9 of 10 patients associated with HHV-6 reactivation before GvHD (P = 0.006) and HHV-6 was the only infection with such an association.
  
  
  CONCLUSIONS
  HHV-6 frequently reactivates after pediatric SCT around the time of mononuclear cell engraftment and is associated with an increased severity of GvHD. HHV-6 may explain fever of unknown origin in 30% of the patients early after SCT. Assessment of HHV-6 reactivation in patients early after SCT can be instrumental for clinical decision making.
authors.affiliation: From the *Department of Pediatrics, †Department of Medical Microbiology, ‡Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands; and §Division of Hematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Dirk H J
authors.initials: DH
authors.lastname: Verhoeven
authors.forename: Eric C J
authors.initials: EC
authors.lastname: Claas
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Jol-van der Zijde
authors.forename: Joyphi C P
authors.initials: JC
authors.lastname: Thijssen
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
authors.forename: Robbert G M
authors.initials: RG
authors.lastname: Bredius
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Aloys C M
authors.initials: AC
authors.lastname: Kroes
authors.forename: R Maarten
authors.initials: RM
authors.lastname: Egeler
authors.forename: Marco W
authors.initials: MW
authors.lastname: Schilham
authors.forename: Maarten J D
authors.initials: MJ
authors.lastname: van Tol
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005076:Exanthema; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications / Q000453:epidemiology / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D015654:Herpesvirus 6, Human; D006801:Humans; D007223:Infant; D007962:Leukocytes; D008297:Male; D012307:Risk Factors; D019349:Roseolovirus Infections / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology; D014766:Viremia; D014775:Virus Activation; D055815:Young Adult