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

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 × 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.

• Authors: 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
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 18 Issue 15 Pg. 4183-90 (Aug 01 2012) ISSN: 1557-3265 [Electronic] United States
• PMID: 22675173 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• DNA, Viral
• Steroids
• Etoposide
• Asparaginase
• Ifosfamide
• Methotrexate

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Asparaginase (administration & dosage, adverse effects)
• DNA, Viral (blood, genetics)
• Epstein-Barr Virus Infections (blood, drug therapy, virology)
• Etoposide (administration & dosage, adverse effects)
• Female
• Herpesvirus 4, Human (genetics)
• Humans
• Ifosfamide (administration & dosage, adverse effects)
• Kaplan-Meier Estimate
• Leukopenia (chemically induced)
• Lymphoma, Extranodal NK-T-Cell (blood, drug therapy, virology)
• Male
• Methotrexate (administration & dosage, adverse effects)
• Middle Aged
• Nasal Mucosa (drug effects, pathology, virology)
• Neutropenia (chemically induced)
• Prognosis
• Prospective Studies
• Steroids (administration & dosage, adverse effects)
• Treatment Outcome
• Young Adult