title: Management of Epstein-Barr virus (EBV) reactivation after allogeneic stem cell transplantation by simultaneous analysis of EBV DNA load and EBV-specific T cell reconstitution.
abstract: BACKGROUND
  Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation and may progress to life-threatening lymphoproliferative disease (EBV-LPD) in the absence of adequate EBV-specific T cell immunity. Quantification of EBV DNA load in asymptomatic individuals who are at risk is a useful (although not entirely predictive) indicator of progression to EBV-LPD and guide for preemptive treatment with CD20 antibodies.
  
  
  METHODS
  With the aim of improving the identification of patients at risk, we retrospectively analyzed, within a cohort of 25 consecutive allogeneic stem cell transplant recipients at risk for EBV-LPD, the pattern of T cell reconstitution during EBV reactivation in all preemptively treated patients (8 patients).
  
  
  RESULTS
  In 6 of 8 cases, a significant T cell reconstitution (i.e., a CD3+ T cell count of >300 cells/microL) was documented during EBV reactivation, which included an expansion of EBV-specific memory T cells, as shown by human leukocyte antigen class I tetramer analysis. Additional evidence for the antiviral potential of this T cell reconstitution was obtained prospectively from a cohort of 14 consecutive allogeneic stem cell transplant recipients at risk for EBV-LPD. EBV reactivation occurred in 3 patients. Preemptive treatment was successfully withheld for 2 of these patients in light of concurrent (EBV-specific) T cell recovery.
  
  
  CONCLUSIONS
  We conclude that analysis of the level of (EBV-specific) T cell reconstitution during EBV reactivation is an important second parameter, in addition to quantification of EBV DNA load, that will be instrumental in a more accurate definition of patients at risk for EBV-LPD who, given their immunoincompetence, will be most certainly dependent on preemptive interventions.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nicola E
authors.initials: NE
authors.lastname: Annels
authors.forename: Jayant S
authors.initials: JS
authors.lastname: Kalpoe
authors.forename: Robbert G M
authors.initials: RG
authors.lastname: Bredius
authors.forename: Eric C
authors.initials: EC
authors.lastname: Claas
authors.forename: Aloys C M
authors.initials: AC
authors.lastname: Kroes
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hislop
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
authors.forename: R Maarten
authors.initials: RM
authors.lastname: Egeler
authors.forename: Maarten J D
authors.initials: MJ
authors.lastname: van Tol
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood*; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D008212:Lymphocyte Depletion; D012189:Retrospective Studies; D000069283:Rituximab; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D019562:Viral Load; D014775:Virus Activation / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D004279:DNA, Viral; D007155:Immunologic Factors; D000069283:Rituximab