Pretreatment EBV-DNA Copy Number Is Predictive of Response and Toxicities to SMILE Chemotherapy for Extranodal NK/T-cell Lymphoma, Nasal Type

PURPOSE: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is an Epstein-Barr virus (EBV)-associated lymphoma for which a new chemotherapeutic regimen called SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) recently showed promising results. EXPERIMENTAL DESIGN: The amount of EBV-DNA was prospectively measured in whole-blood and plasma samples by real-time quantitative PCR from 26 patients registered in the SMILE phase II study. RESULTS: Before treatment, the EBV-DNA was detected in 22 samples of whole blood with a median number of 3,691 copies/mL (range: 0-1.14 × 10(7)), but 15 samples of plasma with a median of 867 copies/mL (range: 0-1.27 × 10(7)). Results of these 2 measurements of EBV-DNA well correlated (R(2) = 0.994, P < 0.001). The overall response rate to SMILE was significantly higher in patients with less than 10(5) copies/mL of EBV-DNA in whole blood at enrollment (90% vs. 20%, P = 0.007) and in patients with less than 10(4) copies/mL of EBV-DNA in plasma (95% vs. 29%, P = 0.002). The incidence of grade 4 toxicity of SMILE other than leukopenia/neutropenia was significantly higher in patients with 10(5) copies/mL of EBV-DNA or more in whole blood (100% vs. 29%, P = 0.007) than that of others and in patients with 10(4) copies/mL or more in plasma (86% vs. 26%, P = 0.002). CONCLUSIONS: These findings suggest that whole blood is more sensitive for clinical use than plasma. The EBV-DNA amount in whole blood was useful for predicting tumor response, toxicity, and prognosis after SMILE chemotherapy for ENKL.