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Lymphoma

Quantification of circulating Epstein–Barr virus DNA in NK/T-cell lymphoma treated with the SMILE protocol: diagnostic and prognostic significance

Abstract

Circulating Epstein–Barr virus (EBV) DNA is a biomarker of EBV-associated malignancies. Its significance in natural killer/T-cell lymphoma treated with the novel regimen SMILE was investigated. EBV DNA was quantified with a World Health Organization EBV standard in 910 plasma samples collected during 230 courses of SMILE in 56 patients. Median presentation EBV DNA was 1900 (0–1.4 × 107) IU/ml. Presentation EBV DNA was significantly associated with tumor load and treatment response. To examine lymphoma chemosensitivity, EBV DNA changes after SMILE were evaluated. EBV DNA after SMILE (I) significantly correlated with tumor load and treatment response. Two dynamic parameters were further analyzed: negative EBV DNA after SMILE (I) and EBV DNA change patterns during treatment (A: persistently undetectable; B: persistently detectable<presentation; C: persistently detectable>presentation). Negative EBV DNA after SMILE (I) and pattern A EBV DNA change significantly correlated with lower tumor load and superior outcome. Multivariate analysis involving presentation features, international prognostic index (IPI), Korean prognostic score and EBV DNA parameters showed that negative EBV DNA after SMILE (I) had the most significant impact (P<0.001) on overall survival and pattern A EBV DNA change had the most significant impact (P=0.002) on disease-free survival. Presentation EBV DNA, IPI and Korean prognostic scores were not independent prognostic factors.

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Acknowledgements

The authors thank Stanley Yeung for assistance in statistical analyses.

Author contributions

YLK designed the study, treated the patients, wrote and approved the manuscript. AP designed the study, performed the experiments, wrote and approved the manuscript. AYHL treated the patients, wrote and approved the manuscript. CSC treated the patients, wrote and approved the manuscript. ET treated the patients, wrote and approved the manuscript.

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Correspondence to Y-L Kwong.

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Kwong, YL., Pang, A., Leung, A. et al. Quantification of circulating Epstein–Barr virus DNA in NK/T-cell lymphoma treated with the SMILE protocol: diagnostic and prognostic significance. Leukemia 28, 865–870 (2014). https://doi.org/10.1038/leu.2013.212

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