Diagnostic and prognostic implications of circulating cell-free Epstein-Barr virus DNA in natural killer/T-cell lymphoma.

Abstract

Natural killer/T-cell (NK/T-cell) lymphoma is a highly aggressive tumor for which no serological tumor marker has yet been established to be useful clinically. We investigated the potential of circulating EBV DNA as a tumor marker for this malignancy. A real-time quantitative PCR assay was used to measure circulating EBV DNA. Plasma EBV DNA levels were measured in 18 patients with NK/T-cell lymphoma at presentation and during therapy. Plasma EBV DNA was detected in 17 of the 18 patients (median, 659 copies/ml; interquartile range, 181-17,042 copies/ml) but in none of 35 control subjects (p < 0.0001). Serial measurements of plasma EBV DNA levels during therapy showed a close correlation between clinical response and changes in plasma EBV DNA levels. Clinically responding patients showed a fall of plasma EBV DNA levels to low or undetectable levels, whereas those who failed therapy showed a rapid increase in plasma EBV DNA levels. Most importantly, patients with high baseline plasma EBV DNA levels (> or = 600 copies/ml) demonstrated a significantly inferior survival than those with low baseline plasma EBV DNA (< 600 copies/ml; 21% versus 78%; P = 0.024). Plasma EBV DNA, as measured by real-time quantitative PCR, is a useful tumor marker for diagnosis, disease monitoring, and prediction of outcome in patients with NK/T-cell lymphoma.