Bradley M Haverkos1, Alejandro A Gru2, Susan M Geyer3, Anissa K Bingman4, Jessica A Hemminger5, Anjali Mishra6, Henry K Wong7, Preeti Pancholi5, Aharon G Freud8, Michael A Caligiuri9, Robert A Baiocchi9, Pierluigi Porcu10. 1. Division of Hematology, University of Colorado, Denver, CO. Electronic address: bradley.haverkos@ucdenver.edu. 2. Department of Pathology, University of Virginia, Charlottesville, VA. 3. Department of Pediatrics Health Informatics Institute, University of South Florida, Tampa, FL. 4. Center for Biostatistics, The Ohio State University, Columbus, OH. 5. Department of Pathology, The Ohio State University, Columbus, OH. 6. 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. 7. Department of Dermatology, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR. 8. The Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH. 9. 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. 10. 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.
Abstract
INTRODUCTION: 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 AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.
INTRODUCTION: 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 ASCTCL are unknown. PATIENTS AND METHODS: Patients (n = 46; 2006-2013) with ASCTCL (≥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. RESULTS: Plasma EBV-DNA and pCMVd were detected in 37% (17 of 46) and 17% (8 of 46) of ASCTCLpatients, 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). CONCLUSION: 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 ASCTCL.
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Authors: Bradley M Haverkos; Ying Huang; Alejandro Gru; Preeti Pancholi; Aharon G Freud; Anjali Mishra; Amy S Ruppert; Robert A Baiocchi; Pierluigi Porcu Journal: Int J Cancer Date: 2017-04-15 Impact factor: 7.396
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