title: Plasma Epstein-Barr virus (EBV) DNA is a biomarker for EBV-positive Hodgkin's lymphoma.
abstract: OBJECTIVE
  Latent Epstein-Barr virus (EBV) genomes are found in the malignant cells of approximately one-third of Hodgkin's lymphoma (HL) cases. Detection and quantitation of EBV viral DNA could potentially be used as a biomarker of disease activity.
  
  
  METHODS
  Initially, EBV-DNA viral load was prospectively monitored from peripheral blood mononuclear cells (PBMC) in patients with HL. Subsequently, we analyzed viral load in plasma from a second cohort of patients. A total of 58 patients with HL (31 newly diagnosed, 6 relapsed, and 21 in long-term remission) were tested. Using real-time PCR, 43 PBMC and 52 plasma samples were analyzed.
  
  
  RESULTS
  EBV-DNA was detectable in the plasma of all EBV-positive patients with HL prior to therapy. However, viral DNA was undetectable following therapy in responding patients (P = 0.0156), EBV-positive HL patients in long-term remission (P = 0.0011), and in all patients with EBV-negative HL (P = 0.0238). Conversely, there was no association seen for the EBV-DNA load measured from PBMC in patients with active EBV-positive HL patients as compared with EBV-negative HL, or patients in long-term remission. EBV-DNA load in matched plasma/PBMC samples were not correlated.
  
  
  CONCLUSIONS
  We show that free plasma EBV-DNA has excellent sensitivity and specificity, and can be used as a noninvasive biomarker for EBV-positive HL and that serial monitoring could predict response to therapy. Additional prospective studies are required to further evaluate the use of free plasma EBV-DNA as a biomarker for monitoring response to treatment in patients with EBV-positive HL.
authors.affiliation: Tumour Immunology Laboratory, Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Department of Haematology, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Maher K
authors.initials: MK
authors.lastname: Gandhi
authors.forename: Eleanore
authors.initials: E
authors.lastname: Lambley
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Burrows
authors.forename: Ujjwal
authors.initials: U
authors.lastname: Dua
authors.forename: Suzanne
authors.initials: S
authors.lastname: Elliott
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
authors.forename: Max
authors.initials: M
authors.lastname: Wolf
authors.forename: Kerrie
authors.initials: K
authors.lastname: Clarke
authors.forename: Craig
authors.initials: C
authors.lastname: Underhill
authors.forename: Tony
authors.initials: T
authors.lastname: Mills
authors.forename: Peter
authors.initials: P
authors.lastname: Mollee
authors.forename: Devinder
authors.initials: D
authors.lastname: Gill
authors.forename: Paula
authors.initials: P
authors.lastname: Marlton
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood*; D020031:Epstein-Barr Virus Infections / Q000097:blood* / Q000821:virology; D005260:Female; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006689:Hodgkin Disease / Q000097:blood* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000821:virology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D012307:Risk Factors; D012680:Sensitivity and Specificity; D019562:Viral Load
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral