Epstein-Barr virus DNA load in chronic lymphocytic leukemia is an independent predictor of clinical course and survival
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Carlo Visco1, Erika Falisi1, Ken H. Young2, Michela Pascarella3, Omar Perbellini4, Giuseppe Carli1, Elisabetta Novella1, Davide Rossi5, Ilaria Giaretta1, Chiara Cavallini6, Maria Teresa Scupoli6, Anita De Rossi7,8, Emanuele Stefano Giovanni D’Amore9, Mario Rassu3, Gianluca Gaidano5, Giovanni Pizzolo4, Achille Ambrosetti4 and Francesco Rodeghiero1
1 Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy
2 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
3 Department of Microbiology, San Bortolo Hospital, Vicenza, Italy
4 Section of Hematology, Department of Medicine, University of Verona, Verona, Italy
5 Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy
6 Research Center LURM (University Laboratory of Medical Research), University of Verona, Verona, Italy
7 Section of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
8 Istituto Oncologico Veneto(IOV)-IRCCS, Padova, Italy
9 Department of Pathology, San Bortolo Hospital, Vicenza, Italy
Carlo Visco, email:
Keywords: Epstein-Barr virus, chronic lymphocytic leukemia, CLL, EBV DNA
Received: April 30, 2015 Accepted: May 09, 2015 Published: June 10, 2015
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.
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