Superiority of Epstein-Barr Virus (EBV) DNA in the Plasma over Whole Blood in Prognostication of Extranodal NK/T Cell Lymphoma, Nasal Type (ENKTL)

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.2846-2846
• Main Authors: Ha, Joo Young, Sung, Heungsup, Jung, Ah Ra, Lee, Yoon Sei, Lee, Sang-wook, Ryu, Jin-Sook, Chae, Eun Jin, Kim, Kyoung Won, Huh, Jooryung, Park, Chan-Sik, Kim, Dong-Joon, Kim, Seon-Ok, Suh, Cheolwon, Yoon, Dok Hyun
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-129772

Background Extranodal natural killer T cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma, of which pathogenesis is related to Epstein-Barr virus (EBV) infection. The presence of EBV-DNA in blood is a well-known prognosticator, which is also included in a prognostic model, PINK-E (Kim SJ et al, Lancet Oncol 2016). Furthermore, its presence after treatment is known to be a predictor of the treatment failure (Kim SJ et al, Lancet Haematol 2015). However, no consensus have been made on which blood sample (i.e, whole blood vs. plasma) is best to be used for the test. While EBV in plasma is known to have a higher specificity and sensitivity for EBV-related diseases as compared with EBV in peripheral blood mononuclear cells (Kanakry JA et al., Blood 2016), PINK-E model incorporated EBV status regardless of types of samples. We aimed to compare the prognostic performance of EBV DNA titers from whole blood (WB) and plasma. Method The EBV DNA viral load was measured in both WB and plasma samples by real-time quantitative PCR at the time of diagnosis, during and after completion of planned treatment. DNA was extracted using Artus® EBV RG PCR kit (Qiagen Inc.). The limit of detection level was 2.66 log copies/mL according to the manufacturer. Prognostic accuracy was compared by using time-dependent receiver operating characteristic (ROC) curves and corresponding area under the curve (AUC) values. Results A total of 60 patients with newly diagnosed ENKTL between September 2014 and September 2018 were included in this analysis. Twenty nine patients (48.3%) were in stage I, 6 (10.0%) in stage II, and 25 (41.7%) in stage IV. Forty six (76.7 %) patients had nasal involvement. Among them, 33 patients underwent concurrent chemoradiotherapy with weekly cisplatin and 53 received L-asparaginase containing chemotherapy (VIDL, n=46, 86.8%; SMILE, n=7, 13.2%) as definitive treatment or after chemoradiotherapy. Fifty two patients were evaluable for response: 33 (63.5%) complete response, 9 (17.3%) partial response, and 10 (19.2%) progressive disease. With a median follow-up duration of 34.1 months (range, 1.2-57.5 months), 2-year progression-free survival (PFS) and overall survival (OS) rates were 55.0% and 63.0%, respectively. EBV-DNA was detected in 37 (61.7%) in pretreatment WB and 23 patients (38.3%) in plasma samples respectively (Table 1). There was moderate agreement (ƙ=0.49) between the tests. Discordant results were noted in 16 (26.7%) patients, 15 of whom we