Subject(s)
Interferon-alpha/administration & dosage , Leukocytes, Mononuclear/physiology , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Adjuvants, Pharmaceutic/administration & dosage , Adult , Aged , Cells, Cultured , Drug Dosage Calculations , Female , Humans , Interferon Regulatory Factors/genetics , Interferon alpha-2 , Janus Kinases/metabolism , Male , Middle Aged , Pilot Projects , Prospective Studies , STAT Transcription Factors/metabolism , Signal Transduction , Young AdultABSTRACT
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.
Subject(s)
Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/genetics , Lymphoma, T-Cell, Cutaneous/diagnosis , Lymphoma, T-Cell, Cutaneous/mortality , Viral Load , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers , Biopsy , DNA, Viral , Epstein-Barr Virus Infections/complications , Female , Follow-Up Studies , Humans , Lymphoma, T-Cell, Cutaneous/etiology , Lymphoma, T-Cell, Cutaneous/therapy , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Skin/pathology , Survival Analysis , Treatment OutcomeABSTRACT
During 1993-2002, cats accounted for 2.7% of rabid terrestrial animals in New York but for one third of human exposure incidents and treatments. Nonbite exposures and animals of undetermined rabies status accounted for 54% and 56%, respectively, of persons receiving rabies treatments.
