Prospective Measurement of EBV-DNA in Plasma and Peripheral Blood Mononuclear Cells of Extranodal NK/T-Cell Lymphoma, Nasal Type.
2009
Abstract 135 Background: Peripheral blood of patients with extranodal NK/T-cell lymphoma, nasal type (ENKL) contains fragmented Epstein-Barr virus (EBV) DNA. Measurement of the circulating viral DNA load has been reported to be useful for the diagnosis, monitoring and prognostication of the disease. However, there are two different subjects for analysis, plasma/serum component and mononuclear cells (MNC). Most reports do not compare both samples from the same patients, and are biased by a retrospective manner of accrual. Therefore, it remains unclear which samples are more useful subjects. Materials and Methods: To evaluate clinical significance of peripheral blood EBV-DNA copy number for ENKL, we conducted a prospective study to analyze EBV-DNA with quantitative polymerase chain reaction. Inclusion criteria are as follows: (1) Diagnosis of ENKL or aggressive NK-cell leukemia by biopsy or cytology. (2) Patients without other serious complications and those tolerable for chemotherapy and/or radiotherapy. (3) No prior history of chemotherapy or radiotherapy. (4) Patients with written informed consent. Primary endpoint was a prognostic value of EBV-DNA copy number to predict 2-year overall survival. Secondary endpoints were comparison of EBV-DNA copy number and pretreatment characteristics and prognostic capability of EBV-DNA during/after treatments. Three times of analysis, pre-treatment, mid-treatment, post-treatment, at central laboratory was to be performed for each patient. Results: A total of 33 patients were registered from June 2004 to March 2007. All patients were diagnosed with ENKL and male/female ratio was 21/12. The median age was 56 years old, ranging from 18 to 81. 19 patients were in stage IE, 3 in stage IIE, and 11 in stage IV. 13 patients had B-symptom and 14 had elevated serum LDH level. ECOG performance status was low (0–2) in 29 patients, but was 3 in 2 patients. IPI was high-intermediate/high in 11. First line treatment included concurrent chemoradiotherapy in 16, radiotherapy followed by chemotherapy in 8, and chemotherapy alone in 6. Pretreatment MNC and plasma EBV-DNA were detectable in 6 and 14 patients, respectively. The maximum copy numbers were 780 copies/microgram DNA for MNC and 71000 copies/mL for plasma. Significant correlation was observed between mononuclear and plasma EBV-DNA copies (r = 0.8741, P Conclusions: Our study shows pretreatment plasma EBV-DNA copy number is a good indicator for both response to treatment and overall survival. Measurement of the plasma EBV-DNA is useful for prospective clinical trials and general practice. Disclosures: Oshimi: Eisai Pharmaceutical Company: Employment.
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