title: Epstein-Barr virus DNA load in chronic lymphocytic leukemia is an independent predictor of clinical course and survival.
abstract: The relation between Epstein-Barr virus (EBV) DNA load and clinical course of patients with chronic lymphocytic leukemia (CLL) is unknown. We assessed EBV DNA load by quantitative PCR at CLL presentation in mononuclear cells (MNC) of 220 prospective patients that were enrolled and followed-up in two major Institutions. In 20 patients EBV DNA load was also assessed on plasma samples. Forty-one age-matched healthy subjects were tested for EBV DNA load on MNC. Findings were validated in an independent retrospective cohort of 112 patients with CLL. EBV DNA load was detectable in 59%, and high (≥2000 copies/µg DNA) in 19% of patients, but it was negative in plasma samples. EBV DNA load was significantly higher in CLL patients than in healthy subjects (P < .0001). No relation was found between high EBV load and clinical stage or biological variables, except for 11q deletion (P = .004), CD38 expression (P = .003), and NOTCH1 mutations (P = .05). High EBV load led to a 3.14-fold increase in the hazard ratio of death and to a shorter overall survival (OS; P = .001). Poor OS was attributable, at least in part, to shorter time-to-first-treatment (P = .0008), with no higher risk of Richter's transformation or second cancer. Multivariate analysis selected high levels of EBV load as independent predictor of OS after controlling for confounding clinical and biological variables. EBV DNA load at presentation is an independent predictor of OS in patients with CLL.
authors.affiliation: Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
authors.affiliation: Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Falisi
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.affiliation: Department of Microbiology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Pascarella
authors.affiliation: Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Omar
authors.initials: O
authors.lastname: Perbellini
authors.affiliation: Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carli
authors.affiliation: Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Novella
authors.affiliation: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Giaretta
authors.affiliation: Research Center LURM (University Laboratory of Medical Research), University of Verona, Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cavallini
authors.affiliation: Research Center LURM (University Laboratory of Medical Research), University of Verona, Verona, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Scupoli
authors.affiliation: Section of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.|Istituto Oncologico Veneto(IOV)-IRCCS, Padova, Italy.
authors.forename: Anita
authors.initials: A
authors.lastname: De Rossi
authors.affiliation: Department of Pathology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Emanuele Stefano Giovanni
authors.initials: ES
authors.lastname: D'Amore
authors.affiliation: Department of Microbiology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Rassu
authors.affiliation: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.affiliation: Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pizzolo
authors.affiliation: Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Achille
authors.initials: A
authors.lastname: Ambrosetti
authors.affiliation: Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Rodeghiero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D004279:DNA, Viral / Q000097:blood / Q000235:genetics*; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D019562:Viral Load / Q000235:genetics*
chemical_list: D004279:DNA, Viral
keywords: CLL; EBV DNA; Epstein-Barr virus; chronic lymphocytic leukemia