Whole blood Epstein-Barr virus DNA load as a diagnostic and prognostic surrogate: extranodal natural killer/T-cell lymphoma

Abstract

We investigated the value of Epstein-Barr virus (EBV) DNA load in unfractionated whole blood for the diagnosis and prognosis of EBV-associated lymphoma. From July 2004 to July 2007, we compared EBV DNA loads in 101 patients with lymphoma and 105 control individuals. The median copy number of EBV was higher in patients with EBV-positive lymphoma (p<0.001). In patients with natural killer (NK)/T-cell lymphomas, the median EBV DNA load at presentation was significantly related to the stage (p = 0.011) and response (p = 0.026). The newly proposed classification model for NK/T cell lymphoma showed EBV DNA load differed significantly between patients with upper and extra-upper aerodigestive tracts (p = 0.017). In 16 patients with NK/T-cell lymphoma monitored serially, EBV DNA load correlated well with the treatment response and clinical course. Further prospective studies are required to evaluate the diagnosing and monitoring role of whole blood EBV DNA for uniformly treated patients.

Clinical implications of plasma Epstein-Barr virus DNA in early-stage extranodal nasal-type NK/T-cell lymphoma patients receiving primary radiotherapy

“…[22][23][24][38][39][40][41] Several small cohort of studies have demonstrated that a high EBV-DNA load is associated with advanced stage, poor clinical response, B-symptoms, and elevated LDH levels in NKTCL (supplemental Table 1, available on the Blood Web site; see the Supplemental Materials link at the top of the online article). [31][32][33][34][35] Our results confirmed that pretreatment EBV-DNA levels correlate with B-symptoms, elevated LDH levels, and an IPI score of 1-2 in early-stage NKTCL. Interestingly, the median concentrations of EBV-DNA (491 copies/mL) in this series were similar to previous studies in low-risk patients who presented with early-stage disease, in which EBV-DNA was detected at relatively low levels (median, 349 or 659 copies/ mL).…”

“…31,33 Preliminary results in a small cohort of NKTCL patients have shown that patients with high concentrations of pretreatment EBV-DNA and detectable EBV-DNA levels after treatment have an extremely poor survival rate. [31][32][33][34][35] In this large series of early-stage patients with a favorable prognosis, a survival difference in patients with various EBV-DNA loads was also observed. The pretreatment EBV-DNA level of Յ 500 copies/mL and undetectable EBV-DNA levels after treatment predicted better survival rates in patients with early-stage NKTCL.…”

“…31,33 In contrast, significantly higher EBV-DNA levels (median, 6.36 ϫ 10 4 or 6.1 ϫ 10 7 copies/mL) have been observed in high-risk patients with advanced-stage disease or tumors that are located in the extra-upper aerodigestive tract. 32,34 NKTCL is closely associated with EBV infection. The positivity of EBV in the tumor tissue has been shown to be Ͼ 90%, and plasma EBV-DNA is detected in the majority (Ͼ 80%) of patients with NKTCL.…”

“…[27][28][29][30] Because of the rarity of the disease, the correlation between EBV-DNA levels and prognosis has been explored in small cohorts (n Ͻ 40) of NKTCL patients with different pathologic subtypes, clinical stages, primary locations, and treatment regimens. [31][32][33][34][35] The predictive value of potential biomarkers is dependent on the primary treatment, especially with the use of primary radiotherapy for earlystage NKTCL. Therefore, we performed a prospective study to ascertain the correlation between plasma EBV-DNA levels with clinical features and survival in early-stage NKTCL patients treated with primary radiotherapy.…”

Prognostic relevance of pretransplant Deauville score on PET-CT and presence of EBV DNA in patients who underwent autologous stem cell transplantation for ENKTL

“…15,16 The test used hybridization probes to detect a gene fragment encoding a single copy of the EBV gene EBNA 1. The primers and probes in the kit were specific for amplifying and detecting the EBV DNA.…”