title: The impact of monitoring Epstein-Barr virus PCR in paediatric bone marrow transplant patients: can it successfully predict outcome and guide intervention?
abstract: BACKGROUND
  Epstein-Barr virus (EBV) associated lymphoproliferative disease is a complication of haemopoietic stem cell transplantation (HSCT). In certain groups (unrelated and mismatched donor transplants, T-cell depleted) the risk may be as high as 25% with significant morbidity and mortality. Strategies to predict the impending development of this disorder and allow early intervention have therefore assumed importance. We routinely screen the peripheral blood of all recipients of allogeneic HSCT to detect EBV DNA by quantitative polymerase chain reaction (PCR) technology and report here how this correlates with clinical disease and management.
  
  
  METHODS
  Data on 28 successive patients who underwent HSCT at our institution were reviewed. The relationship between EBV reactivation demonstrated by quantitative PCR and development of post transplant lymphoproliferative disease (PTLD) was determined.
  
  
  RESULTS
  EBV reactivation occurred in 68% of patients, however only 7% developed clinical PTLD. Patients with high level reactivation (n = 9) had more frequent episodes of reactivation and all patients who progressed to overt PTLD were found in this group. In contrast none of those patients with low level reactivation (n = 10) or persistently negative results (n = 9) showed any signs of clinical disease. Anti-CD20 monoclonal antibody (Rituximab) therapy was instigated in both cases of proven PTLD and three cases of high level reactivation with successful outcomes. Response to treatment was associated with a prompt decline in viral copy number.
  
  
  CONCLUSIONS
  Our results indicate that EBV reactivation is a common occurrence in the paediatric allogeneic transplant setting and that only a proportion of patients will progress to PTLD. Frequent monitoring may help to predict those at highest risk and guide intervention.
authors.affiliation: Department of Haematology and Bone Marrow Transplantation, Manchester Royal Infirmary, Pendlebury, Manchester, UK. hayleygreenfield@tiscali.co.uk
authors.forename: Hayley M
authors.initials: HM
authors.lastname: Greenfield
authors.forename: Maged I
authors.initials: MI
authors.lastname: Gharib
authors.forename: Andrew J L
authors.initials: AJ
authors.lastname: Turner
authors.forename: Malcolm
authors.initials: M
authors.lastname: Guiver
authors.forename: Trevor
authors.initials: T
authors.lastname: Carr
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Will
authors.forename: Robert F
authors.initials: RF
authors.lastname: Wynn
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D019562:Viral Load; D014775:Virus Activation
chemical_list: D004279:DNA, Viral