title: Epstein-Barr virus (EBV) reactivation in allogeneic stem-cell transplantation: relationship between viral load, EBV-specific T-cell reconstitution and rituximab therapy.
abstract: BACKGROUND
  Monitoring of Epstein-Barr virus (EBV) reactivation after allogeneic hematopoietic stem-cell transplantation markedly improved with quantitative real-time polymerase chain reaction amplification of EBV DNA and visualization of EBV-specific CD8+ T cells with peptide-human leukocyte antigen (HLA) class I tetramers. We decided to combine these methods to evaluate posttransplant EBV reactivation and rituximab therapy.
  
  
  METHODS
  We followed 56 patients treated with an HLA-genoidentical sibling (n=32), an HLA-matched unrelated donor (MUD, n=19), or an unrelated cord-blood transplant (n=5). EBV DNA was quantified in plasma and in peripheral blood mononuclear cells (PBMC). Patient CD8+ T cells were stained with a panel of eight tetramers.
  
  
  RESULTS
  EBV DNA was detected in half of the patients, mainly in the MUD group (17/19). In 19 patients, viral DNA was detected only in the cellular compartment. All patients who controlled reactivation without rituximab and despite a viral load of greater than 500 genome equivalents (gEq)/150,000 PBMC mounted an EBV-specific CD8+ T-cell response in greater than 1.4% of CD3+CD8+ T cells. Plasmatic EBV genome was found in nine patients preceded by a high cellular viral load. Three of these patients controlled the reactivation before or without the introduction of rituximab, and they all developed a significant and increasing EBV-specific T-cell response. Patients with EBV-specific T cells at the onset of reactivation controlled viral reactivation without rituximab.
  
  
  CONCLUSIONS
  This study emphasizes the benefit of an early and close monitoring of EBV reactivation and CD8+-specific immune responses to initiate rituximab only when necessary and before the immune response becomes overwhelmed by the viral burden.
authors.affiliation: Laboratoire d'Immunologie et d'Histocompatibilité, Unité INSERM U396, Institut Universitaire d'Hématologie, AP/HP, Hôpital Saint-Louis, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Clave
authors.forename: Félix
authors.initials: F
authors.lastname: Agbalika
authors.forename: Véronique
authors.initials: V
authors.lastname: Bajzik
authors.forename: Régis
authors.initials: R
authors.lastname: Peffault de Latour
authors.forename: Mélanie
authors.initials: M
authors.lastname: Trillard
authors.forename: Claire
authors.initials: C
authors.lastname: Rabian
authors.forename: Catherine
authors.initials: C
authors.lastname: Scieux
authors.forename: Agnès
authors.initials: A
authors.lastname: Devergie
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.forename: Patricia
authors.initials: P
authors.lastname: Ribaud
authors.forename: Lionel
authors.initials: L
authors.lastname: Adès
authors.forename: Christèle
authors.initials: C
authors.lastname: Ferry
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Hélène
authors.initials: H
authors.lastname: Esperou
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.forename: Hélène
authors.initials: H
authors.lastname: Moins-Teisserenc
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D002648:Child; D020031:Epstein-Barr Virus Infections / Q000628:therapy* / Q000821:virology*; D005312:Fetal Blood / Q000166:cytology; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D019520:Living Donors; D008875:Middle Aged; D011159:Population Surveillance; D011184:Postoperative Period; D000069283:Rituximab; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous; D019562:Viral Load; D014775:Virus Activation
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab