title: Plasma EBV-DNA monitoring in Epstein-Barr virus-positive Hodgkin lymphoma patients.
abstract: Epstein-Barr virus (EBV) is associated with approximately one-third of Hodgkin lymphoma (HL) cases. EBV-DNA is often present in the plasma and whole blood of EBV-associated HL patients. However, the significance of EBV-DNA monitoring is debated. In a cohort of 165 adult HL patients, EBV-DNA viral load was prospectively monitored both in the plasma and whole blood. Diagnostic tissue samples of all patients were histologically reviewed; in 72% nodular sclerosis was detected, 24% presented with mixed cellularity (MC), and 5% had other type of HL. Tissues from 150 patients were also analyzed for the presence of latent EBV infection using in situ hybridization for EBV-encoded RNA (EBER) and immunohistochemistry for latent membrane protein (LMP1). Using these methods, 29 (19%) patients were classified as EBV positive. Using real-time quantitative PCR, 22 (76%) of EBV-positive HL patients had detectable EBV-DNA in the plasma and 19 (66%) patients in whole blood prior to therapy. In the group of EBV-negative HL cases, three (2%) patients had detectable plasma EBV-DNA and 30 (25%) patients whole blood EBV-DNA before treatment. EBV-positive HL was significantly associated with EBV-DNA positivity both in the plasma and whole blood in pretreatment samples, increasing age and MC subtype. Serial analysis of plasma EBV-DNA showed that response to therapy was associated with decline in viral load. Moreover, significantly increased plasma EBV-DNA level recurred before disease relapse in one patient. Our results further suggest that the assessment of plasma EBV-DNA viral load might be of value for estimation of prognosis and follow-up of patients with EBV-positive HL.
authors.affiliation: Department of Clinical Hematology, University Hospital Kralovske Vinohrady, Charles University, Prague, Czech Republic. m.spacek@fnkv.cz
authors.forename: Martin
authors.initials: M
authors.lastname: Spacek
authors.forename: Petr
authors.initials: P
authors.lastname: Hubacek
authors.forename: Jana
authors.initials: J
authors.lastname: Markova
authors.forename: Miroslav
authors.initials: M
authors.lastname: Zajac
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Vernerova
authors.forename: Katerina
authors.initials: K
authors.lastname: Kamaradova
authors.forename: Jan
authors.initials: J
authors.lastname: Stuchly
authors.forename: Tomas
authors.initials: T
authors.lastname: Kozak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018153:Czech Republic / Q000453:epidemiology; D004279:DNA, Viral / Q000097:blood*; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006689:Hodgkin Disease / Q000097:blood / Q000473:pathology / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000097:blood; D055815:Young Adult
chemical_list: D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; C106732:Epstein-Barr virus encoded RNA 2; D012367:RNA, Viral; D014763:Viral Matrix Proteins