title: Frequency and clinical correlates of elevated plasma Epstein-Barr virus DNA at diagnosis in peripheral T-cell lymphomas.
abstract: Epstein-Barr virus (EBV)-encoded RNAs (EBER) in tumor tissue and cell-free plasma EBV-DNA (pEBVd) are detected in EBV-associated lymphomas. Studies have suggested that EBER+ peripheral T-cell lymphomas (PTCL) have worse prognosis but the role of EBV in these neoplasms remains unclear. pEBVd is quantitative and more easily amenable to standardization than EBER, but frequency of pEBVd detection, clinical impact and agreement with EBER status in PTCL are unknown. We retrospectively assessed frequency of detectable pre-treatment pEBVd, presence of EBER in tumor tissue, and outcomes in 61 of 135 EBV-assessable PTCL patients. Fifteen of 61 patients (24.5%, 95% CI: 14-37%) were pre-treatment pEBVd+, with no significant differences in baseline characteristics or treatment between pEBVd+ and pEBVd- patients. EBER-ISH was performed on 10 pEBVd+ and 35 pEBVd- tumors. All 10 pEBVd+ patients were EBER+, but 9 pEBVd- patients were also EBER+. With median follow up of 24 months (range 1-96), overall survival (OS) was shorter in pEBVd+ compared to pEBVd- patients (13 vs. 72 months; p = 0.04). In our retrospective study, pre-treatment pEBVd was elevated in 25% of PTCL patients, was highly specific for EBER+ tumors, and was associated with shorter survival. pEBVd should be further explored as a prognostic variable and tumor biomarker in PTCL.
authors.affiliation: Division of Hematology, University of Colorado, Aurora, CO.
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Haverkos
authors.affiliation: Division of Hematology, The Ohio State University, Columbus, OH.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, VA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gru
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH.
authors.forename: Preeti
authors.initials: P
authors.lastname: Pancholi
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH.|Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH.
authors.forename: Aharon G
authors.initials: AG
authors.lastname: Freud
authors.affiliation: Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH.
authors.forename: Anjali
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Division of Hematology, The Ohio State University, Columbus, OH.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Ruppert
authors.affiliation: Division of Hematology, The Ohio State University, Columbus, OH.|Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Baiocchi
authors.affiliation: Division of Hematology, The Ohio State University, Columbus, OH.|Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Porcu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D004279:DNA, Viral / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification* / Q000472:pathogenicity; D006801:Humans; D017403:In Situ Hybridization; D016411:Lymphoma, T-Cell, Peripheral / Q000097:blood* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral
keywords: EBV; Epstein-Barr virus; PTCL; cell-free DNA; peripheral T-cell lymphoma