Pretreatment EBV-DNA copy number is predictive of response and toxicities to SMILE chemotherapy for extranodal NK/T-cell lymphoma, nasal type

Yoshinori Ito, Hiroshi Kimura, Yoshinobu Maeda, Chizuko Hashimoto, Fumihiro Ishida, Koji Izutsu, Noriyasu Fukushima, Yasushi Isobe, Jun Takizawa, Yuichi Hasegawa, Hajime Kobayashi, Seiichi Okamura, Hikaru Kobayashi, Motoko Yamaguchi, Junji Suzumiya, Rie Hyo, Shigeo Nakamura, Keisei Kawa, Kazuo Oshimi, Ritsuro Suzuki

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Abstract

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 × 107), but 15 samples of plasma with a median of 867 copies/mL (range: 0-1.27 × 107). Results of these 2 measurements of EBV-DNA well correlated (R2 = 0.994, P < 0.001). The overall response rate to SMILE was significantly higher in patients with less than 105 copies/mL of EBV-DNA in whole blood at enrollment (90% vs. 20%, P = 0.007) and in patients with less than 104 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 105 copies/mL of EBV-DNA or more in whole blood (100% vs. 29%, P = 0.007) than that of others and in patients with 104 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.

Original languageEnglish
Pages (from-to)4183-4190
Number of pages8
JournalClinical Cancer Research
Volume18
Issue number15
DOIs
Publication statusPublished - Aug 1 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ito, Y., Kimura, H., Maeda, Y., Hashimoto, C., Ishida, F., Izutsu, K., Fukushima, N., Isobe, Y., Takizawa, J., Hasegawa, Y., Kobayashi, H., Okamura, S., Kobayashi, H., Yamaguchi, M., Suzumiya, J., Hyo, R., Nakamura, S., Kawa, K., Oshimi, K., & Suzuki, R. (2012). Pretreatment EBV-DNA copy number is predictive of response and toxicities to SMILE chemotherapy for extranodal NK/T-cell lymphoma, nasal type. Clinical Cancer Research, 18(15), 4183-4190. https://doi.org/10.1158/1078-0432.CCR-12-1064