title: HHV-6 infection after allogeneic hematopoietic stem cell transplantation: From chromosomal integration to viral co-infections and T-cell reconstitution patterns.
abstract: OBJECTIVE
  Human herpes virus 6 (HHV-6) can reactivate after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and may be associated with significant clinical manifestations.
  
  
  METHODS
  Case control study of HHV-6 infections after allo-HSCT. Chromosomal integration (ciHHV-6) for viral loads ≥ 5.5-log10 copies/mL was investigated. Viral co-infections, T-cell recovery, risk factors and outcome were compared in HHV-6- and non-HHV-6-infected patients. Antiviral treatment strategies were reviewed.
  
  
  RESULTS
  Among 366 adult allo-HSCT recipients, 75 HHV-6 infections occurred. Three (4%) recipients were ciHHV-6. HHV-6 infections were associated with CMV (p = 0.05; sdHR 1.73, CI 0.99-3.02) and/or BKV infections (p < 0.0001; sdHR 4.63, CI 2.04-10.53) but not EBV reactivation (p = 0.34). A slower CD8+ T-cells recovery was observed until 6 months after allo-HSCT in the HHV-6-infected group (p < 0.001), independently of acute and/or chronic graft-versus-host disease. The overall probability of survival after allo-HSCT was diminished for active HHV-6-infected patients (p = 0.0326). Cord blood unit recipients had a higher risk of developing HHV-6 infection compared to bone marrow recipients (p = 0.0007; sdHR 3.82, CI 1.76-8.27). Anti-HHV-6 treatment achieved complete response in only 2/3 of the cases.
  
  
  CONCLUSIONS
  In this series of allo-HSCT recipients, 4% were ciHHV-6, active HHV-6 infection was likely associated with CMV and BKV co-reactivations, delayed CD8+ T-cell recovery and poorer outcome.
authors.affiliation: Hematology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Quintela
authors.affiliation: Virology Laboratory, Laboratoire de Virologie Est, Hospices Civils de Lyon, F-69677 Bron, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Escuret
authors.affiliation: Infectious Diseases Department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, F-69004 Lyon, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Roux
authors.affiliation: Sorbonne Universités, UPMC, CIMI-Paris UMRS CR7, Inserm U1135, PVI Team, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Bonnafous
authors.affiliation: Hematology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Lila
authors.initials: L
authors.lastname: Gilis
authors.affiliation: Hematology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Barraco
authors.affiliation: Hematology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Labussière-Wallet
authors.affiliation: Hematology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Duscastelle-Leprêtre
authors.affiliation: Hematology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Franck-Emmanuel
authors.initials: FE
authors.lastname: Nicolini
authors.affiliation: Hematology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.affiliation: Infectious Diseases Department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, F-69004 Lyon, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Chidiac
authors.affiliation: Infectious Diseases Department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, F-69004 Lyon, France; Inserm U1111 CIRI, Claude Bernard Lyon I University, Lyon, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Ferry
authors.affiliation: Virology Laboratory, Laboratoire de Virologie Est, Hospices Civils de Lyon, F-69677 Bron, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Frobert
authors.affiliation: Hematology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Morisset
authors.affiliation: Cellular Immunology Laboratory, Hôpital E. Herriot, Hospices Civils de Lyon, F-69003 Lyon, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Poitevin-Later
authors.affiliation: Cellular Immunology Laboratory, Hôpital E. Herriot, Hospices Civils de Lyon, F-69003 Lyon, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Monneret
authors.affiliation: Hematology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.affiliation: Infectious Diseases Department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, F-69004 Lyon, France; Inserm U1111 CIRI, Claude Bernard Lyon I University, Lyon, France. Electronic address: florence.ader@chu-lyon.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Ader
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D060085:Coinfection / Q000453:epidemiology / Q000473:pathology / Q000821:virology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D015654:Herpesvirus 6, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019349:Roseolovirus Infections / Q000453:epidemiology* / Q000473:pathology* / Q000821:virology; D014184:Transplantation, Homologous / Q000009:adverse effects*; D014775:Virus Activation; D016662:Virus Integration; D055815:Young Adult
keywords: BK virus; Chromosomally integrated HHV-6; Cytomegalovirus; Hematopoietic stem cell transplantation; Human herpes virus 6; T lymphocytes