Clinical Research Papers:
Prognostic impact of Epstein-Barr virus (EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia
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Jin-Hua Liang1,*, Rui Gao2,*, Yi Xia1, Robert Peter Gale3, Rui-Ze Chen1, Yu-Qiong Yang1, Li Wang1, Xiao-Yan Qu1, Hai-Rong Qiu1, Lei Cao1, Min Hong1, Rong Wang1, Yan Wang1, Lei Fan1, Yao-Yu Chen1, Zhi-Bin Hu4, Jian-Yong Li1,5 and Wei Xu1
1 Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
2 Nanjing Medical University, Nanjing, China
3 Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom
4 Department of Epidemiology and Biostatistics, Nanjing Medical University, School of Public Health, Nanjing, China
5 Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
* These authors have contributed equally to this work
Wei Xu, email:
Jian-Yong Li, email:
Keywords: chronic lymphocytic leukemia; Epstein-Barr virus; prognosis
Received: July 26, 2015 Accepted: October 09, 2015 Published: November 02, 2015
Epstein-Barr virus (EBV)-DNA is detected in the blood of some persons with chronic lymphocytic leukemia (CLL) at diagnosis. Whether this is important in the development or progression of CLL is controversial. We interrogated associations between blood EBV-DNA copy number and biological and clinical variables in 243 new-diagnosed consecutive subjects with CLL. Quantification of EBV-DNA copies was done by real-time quantitative PCR (RQ-PCR). All subjects had serological evidence of prior EBV-infection. However, only 24 subjects (10%) had a EBV-DNA-positive test at diagnosis. EBV-DNA-positive subjects at diagnosis had lower hemoglobin concentrations and platelet levels, higher thymidine kinase-1 and serum ferritin levels, un-mutated IGHV genes and a greater risk of Richter transformation compared with EBV-DNA-negative subjects. Percent CD20-, CD148- and ZAP70-positive cells and mean fluorescence intensity (MFI) of each cluster designation were also increased in EBV-DNA-positive subjects at diagnosis. EBV-DNA test positivity was associated with a briefer time-to-treatment interval (HR 1.85; [95% confidence interval, 1.13, 3.03]; P=0.014) and worse survival (HR 2.77; [1.18, 6.49]; P=0.019). Reduction in EBV copies was significantly associated with therapy-response. A positive blood EBV-DNA test at diagnosis and sequential testing of EBV copies during therapy were significantly associated with biological and clinical variables, time-to-treatment, therapy-response and survival. If validated these data may be added to CLL prognostic scoring systems.
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