title: The viral load of Epstein-Barr virus (EBV) DNA in peripheral blood predicts for biological and clinical characteristics in Hodgkin lymphoma.
abstract: OBJECTIVE
  The Epstein-Barr virus (EBV) is present in the malignant Hodgkin/Reed-Sternberg (HRS) cells of 20% to 40% cases of Hodgkin lymphoma (HL) in Western countries. We were interested in the detection and quantification of cell-free plasma EBV-DNA as an indicator of biological and clinical characteristics in EBV-associated HL.
  
  
  METHODS
  EBV was detected in peripheral blood compartments (whole blood, plasma, and mononuclear cells) at diagnosis by real-time PCR for the EBNA (EB nuclear antigen) region (n = 93) and in HRS cells by in situ hybridization for EBV-encoded small RNAs (EBER; n = 63). These data were correlated to histological and clinical characteristics, EBV serology, circulating cell-free DNA, and interleukin (IL)-6 levels.
  
  
  RESULTS
  Detection of EBV-DNA in plasma had a high specificity (90%), but a relatively low sensitivity (65%) to predict for EBV association. The viral load was higher in patients with advanced stage disease, older age in the presence of B-symptoms, and international prognostic score more than 2. The presence of EBV in HRS cells and higher plasma EBV-DNA copy numbers correlated to an increased frequency of tumor-infiltrating CD68+ macrophages in lymph node biopsies. Plasma EBV-DNA load correlated to circulating cell-free DNA and IL-6 levels, and inversely correlated to lymphocyte counts and EBNA1 antibody titers.
  
  
  CONCLUSIONS
  Although the presence of EBV-DNA in peripheral blood cannot be regarded as a surrogate marker for EBER, the plasma EBV-DNA load at HL diagnosis is an indicator of disease activity and biological characteristics associated with negative prognosis. Moreover, the inverse correlation to EBNA1 antibody titers and lymphocyte counts may indicate a reduction in immunosurveillance, favoring the expansion of EBV-HRS cells in HL.
authors.affiliation: Institute of Hematology, Microbiology, and Pathological Anatomy, Catholic University S Cuore, Rome, Italy. stefan.hohaus@rm.unicatt.it
authors.forename: Stefan
authors.initials: S
authors.lastname: Hohaus
authors.forename: Rosaria
authors.initials: R
authors.lastname: Santangelo
authors.forename: Manuela
authors.initials: M
authors.lastname: Giachelia
authors.forename: Barbara
authors.initials: B
authors.lastname: Vannata
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Massini
authors.forename: Annarosa
authors.initials: A
authors.lastname: Cuccaro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.forename: Valeriana
authors.initials: V
authors.lastname: Cesarini
authors.forename: Tonia
authors.initials: T
authors.lastname: Cenci
authors.forename: Francesco
authors.initials: F
authors.lastname: D'Alo
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Voso
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fadda
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Leone
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Larocca
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004279:DNA, Viral / Q000032:analysis*; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000254:growth & development*; D006689:Hodgkin Disease / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019562:Viral Load / Q000502:physiology*; D055815:Young Adult
chemical_list: D004279:DNA, Viral