title: Increased Levels of Plasma Epstein Barr Virus DNA Identify a Poor-Risk Subset of Patients With Advanced Stage Cutaneous T-Cell Lymphoma.
abstract: Outcomes in advanced stage (AS) cutaneous T-cell lymphomas (CTCL) are poor but with great variability. Epstein-Barr virus (EBV) is associated with a subset of non-Hodgkin lymphomas. Frequency of plasma EBV-DNA (pEBVd) detection, concordance with EBV RNA (EBER) in tumor tissue, codetection of plasma cytomegalovirus DNA (pCMVd), and prognostic effect in AS CTCL are unknown.
  
  
  
  Patients (n = 46; 2006-2013) with AS CTCL (≥IIB) were retrospectively studied. pEBVd and pCMVd were longitudinally measured using quantitative real-time polymerase chain reaction. EBER in situ hybridization (ISH) was performed on tumor samples. Survival from time of diagnosis (ToD) and time of progression to AS was assessed.
  
  
  
  Plasma EBV-DNA and pCMVd were detected in 37% (17 of 46) and 17% (8 of 46) of AS CTCL patients, respectively. pCMVd detection was significantly more frequent in pEBVd-positive (pEBVd(+)) than pEBVd(-) patients (35% vs. 7%; P = .038). Tumor tissue for EBER-ISH was available in 14 of 17 pEBVd(+) and 22 of 29 pEBVd(-) patients; 12 of 14 (85.7%) pEBVd(+) patients were EBER(+) versus 0 of 22 pEBVd(-) patients. Frequency of large cell transformation (LCT) tended to be greater in pEBVd(+) patients, but was not significant (10 of 14 pEBVd(+) vs. 10 of 23 pEBVd(-); P = .17). No notable differences in rates of increased levels of serum lactate dehydrogenase (LDH) were observed (17 of 17 pEBVd(+) vs. 27 of 29 pEBVd(-)). pEBVd detection was associated with significantly worse survival from ToD (P = .021) and time of progression to AS (P = .0098).
  
  
  
  Detection of cell-free plasma EBV-DNA was highly concordant with the presence of EBERs in tumor tissue, predicted survival independent of LDH and LCT, and should be further studied as a biomarker in AS CTCL.
authors: Division of Hematology, University of Colorado, Denver, CO. Electronic address: bradley.haverkos@ucdenver.edu.
authors: Bradley M
authors: BM
authors: Haverkos
authors: Department of Pathology, University of Virginia, Charlottesville, VA.
authors: Alejandro A
authors: AA
authors: Gru
authors: Department of Pediatrics Health Informatics Institute, University of South Florida, Tampa, FL.
authors: Susan M
authors: SM
authors: Geyer
authors: Center for Biostatistics, The Ohio State University, Columbus, OH.
authors: Anissa K
authors: AK
authors: Bingman
authors: Department of Pathology, The Ohio State University, Columbus, OH.
authors: Jessica A
authors: JA
authors: Hemminger
authors: The Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH; Division of Dermatology, The Ohio State University, Columbus, OH.
authors: Anjali
authors: A
authors: Mishra
authors: Department of Dermatology, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR.
authors: Henry K
authors: HK
authors: Wong
authors: Department of Pathology, The Ohio State University, Columbus, OH.
authors: Preeti
authors: P
authors: Pancholi
authors: The Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH.
authors: Aharon G
authors: AG
authors: Freud
authors: The Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH; Division of Hematology, The Ohio State University, Columbus, OH.
authors: Michael A
authors: MA
authors: Caligiuri
authors: The Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH; Division of Hematology, The Ohio State University, Columbus, OH.
authors: Robert A
authors: RA
authors: Baiocchi
authors: The Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH; Division of Hematology, The Ohio State University, Columbus, OH. Electronic address: pierluigi.porcu@osumc.edu.
authors: Pierluigi
authors: P
authors: Porcu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D001706:Biopsy; D004279:DNA, Viral; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000821:virology*; D005260:Female; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D012867:Skin / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D004279:DNA, Viral
keywords: Biomarker; CTCL; EBV; MF; Mycosis fungoides; biomarker