Impact of Latent Epstein-Barr Virus Infection on Outcome in Children and Adolescents With Hodgkin's Lymphoma

2005 ◽  
Vol 23 (18) ◽  
pp. 4048-4056 ◽  
Author(s):  
Alexander Claviez ◽  
Markus Tiemann ◽  
Heike Lüders ◽  
Matthias Krams ◽  
Reza Parwaresch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Children And Adolescents ◽  
Hodgkin’S Lymphoma ◽  
Epstein Barr Virus ◽  
Hodgkin's Lymphoma ◽  
Histologic Subtype ◽  
Barr Virus ◽  
Ebv Infection ◽  
Nodular Sclerosis ◽  
Epstein Barr

Purpose The prognostic significance of latent Epstein-Barr virus (EBV) infection in Hodgkin's lymphoma (HL) is debated controversially. Especially in the pediatric age group, no conclusive data are available. Patients and Methods Eight hundred forty-two children and adolescents (median age, 13.7 years) from pediatric multicenter treatment studies HD-90 and HD-95 were studied for latent EBV infection in Hodgkin's and Reed-Sternberg cells by immunostaining against latent membrane protein 1 (LMP-1). Results were compared with established risk factors. Results Two hundred sixty-three patients (31%) were LMP positive. EBV infection correlated with sex (39% male v 23% female; P < .001), histologic subtype (69% mixed cellularity v 22% nodular sclerosis v 6% lymphocyte predominance; P < .001) and young age. With a median follow-up of 4.9 years, 820 patients (97%) are alive. Probability of overall survival at 10 years (± standard deviation) for EBV-negative and -positive patients was 98.1% ± 0.6% and 95.1% ± 1.4%, respectively (P = .017 by log-rank test). A negative effect of EBV infection became evident for patients with nodular sclerosis subtype Bennett II (P = .02), and those treated for advanced stages (P = .003). In multivariate analysis, LMP positivity was an independent factor for adverse outcome (RR = 3.08). Probability of failure-free survival (FFS) in LMP positive and negative patients was 89.1% ± 2.3% and 84.1% ± 3.9%, respectively (P = .86). Conclusion With effective combined treatment modalities in pediatric HL, latent EBV infection has no influence on FFS but is associated with an inferior overall survival in crucial subgroups.

The Impact of Latent Epstein-Barr Virus Infection on Outcome in Children and Adolescents with Hodgkin’s Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3121-3121
Author(s):  
Alexander Claviez ◽  
Markus Tiemann ◽  
Heike Lueders ◽  
Reza Parwaresch ◽  
Guenther Schellong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Children And Adolescents ◽  
Hodgkin’S Lymphoma ◽  
Epstein Barr Virus ◽  
Hodgkin's Lymphoma ◽  
Barr Virus ◽  
Ebv Infection ◽  
Nodular Sclerosis ◽  
Epstein Barr ◽  
The Impact

Abstract The prognostic significance of latent Epstein-Barr virus (EBV) infection in Hodgkin’s lymphoma (HL) is debated controversially. Especially in the pediatric age group, no conclusive data are available due to small series. 842 children and adolescents (55% male) with a median age of 13.7 years (range, 2–20) from consecutive pediatric DAL/GPOH multicenter treatment studies HD-90 and HD-95 were studied for the presence of latent EBV infection in Hodgkin and Reed-Sternberg cells by immunostaining against latent membrane protein 1 (LMP-1). Histology subtypes were as follows: nodular sclerosis (NSHL) 549, mixed cellularity (MCHL) 190, lymphocyte predominance (NLPHL) 90, lymphocyte depletion (LDHL) 6, lymphocyte-rich classical HL (LRCHL) 5, not specified 2. 88 patients had stage I, 470 had stage II, 172 had stage III and 112 had stage IV. B symptoms were present in 274 patients (33%). LMP status was compared with clinical parameters and established risk factors. A total of 263 patients (32%) were LMP positive. EBV infection correlated with gender (male 39% vs. female 23%; p&lt;.001), histological subtype (MCHL 69% vs. NSHL 22% vs. NLPHL 6%; p&lt;.001) and age (&lt;10 years 67% vs ≥10 years 28%, p&lt;.001. With a median follow-up of 4.9 years (0.3–12) 820 patients (97%) are alive. Probability of overall survival at 10 years (±SD) for EBV negative and positive patients was 98±1% and 95±1%, respectively (p=.017 by log-rank test). Probability of failure-free survival (FFS) in LMP positive and negative patients was 89±2% and 84±4%, respectively (p=.86). With respect to LMP status, a negative effect of latent EBV infection on overall survival became evident only for patients treated for advanced stages (p=.003), those with nodular sclerosis subtype Bennett II (p=.02) and B symptoms (p=.05). In a multivariate regression analysis, allocation to treatment group (RR=3.7) and LMP positivity (RR=3.01) were independent factors for overall survival and presence of B symptoms (RR=2.4) for FFS. Under current highly effective polychemotherapy with or without involved field radiotherapy in pediatric HL, latent EBV infection has no influence on FFS in univariate and multivariate analysis. LMP positivity, however, seems to be associated with an inferior overall survival in some subgroups.

Epstein-Barr Virus As a Marker of Survival After Hodgkin's Lymphoma: A Population-Based Study

2005 ◽  
Vol 23 (30) ◽  
pp. 7604-7613 ◽  
Author(s):  
Theresa H.M. Keegan ◽  
Sally L. Glaser ◽  
Christina A. Clarke ◽  
Margaret L. Gulley ◽  
Fiona E. Craig ◽  
...  
Keyword(s):  
San Francisco ◽  
Prognostic Marker ◽  
Hodgkin’S Lymphoma ◽  
Epstein Barr Virus ◽  
Young Patients ◽  
Population Based ◽  
Hodgkin's Lymphoma ◽  
Histologic Subtype ◽  
Barr Virus ◽  
Epstein Barr

Purpose Epstein-Barr virus (EBV) in Hodgkin's lymphoma (HL) cells has been considered as a prognostic marker for this heterogeneous disease, but studies have yielded mixed findings, likely because of selected patient series and failure to acknowledge an effect of age on outcome. This study assessed survival after HL in a population-based cohort large enough to examine the joint effects of EBV with other factors including age, sex, and histologic subtype. Patients and Methods Included were 922 patients with classical HL diagnosed between mid-1988 and 1997 in the Greater San Francisco Bay Area, with archived biopsy specimens assayed for EBV with immunohistochemistry and in situ hybridization. Vital status was followed through December 30, 2003 (median follow-up time, 97 months). Overall and disease-specific survival were analyzed with the Kaplan-Meier method and Cox proportional hazards regression models. Results In children less than 15 years old, EBV presence was suggestively associated (P = .07) with favorable survival. In adults aged 15 to 44 years, EBV did not affect HL outcome, although a protective effect was suggested. In older adults (45 to 96 years), EBV presence nearly doubled the risk of overall and HL-specific mortality but only for patients with nodular sclerosis (NS) histologic subtype (hazard ratio for death = 2.5; 95% CI, 1.5 to 4.3). Conclusion In HL, EBV tumor cell presence is associated with better survival in young patients and poorer survival in older patients with NS, independent of other factors. Variation in outcome by age and histology could indicate biologically distinct disease entities. Evidence that EBV is a meaningful prognostic marker may have therapeutic relevance.

scholarly journals Comparison of three methods for the detection of Epstein-Barr virus in Hodgkin’s lymphoma in paraffin-embedded tissues

2012 ◽  
Vol 7 (1) ◽  
pp. 89-92 ◽  
Author(s):  
ZONG-LI QI ◽  
XI-QUN HAN ◽  
JUN HU ◽  
GUANG-HUA WANG ◽  
JIN-WEI GAO ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Epstein Barr Virus ◽  
Hodgkin's Lymphoma ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Association between Epstein-Barr virus and Hodgkin's lymphoma in Belgium: A pathological and virological study

2007 ◽  
Vol 48 (7) ◽  
pp. 1323-1331 ◽  
Author(s):  
Mounir Trimèche ◽  
Christophe Bonnet ◽  
Sadok Korbi ◽  
Jacques Boniver ◽  
Laurence de Leval
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Epstein Barr Virus ◽  
Hodgkin's Lymphoma ◽  
Barr Virus ◽  
Virological Study ◽  
Epstein Barr

scholarly journals The H3K27me3 demethylase, KDM6B, is induced by Epstein–Barr virus and over-expressed in Hodgkin's Lymphoma

Oncogene ◽  
2011 ◽  
Vol 30 (17) ◽  
pp. 2037-2043 ◽  
Author(s):  
J A Anderton ◽  
S Bose ◽  
M Vockerodt ◽  
K Vrzalikova ◽  
W Wei ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Epstein Barr Virus ◽  
Hodgkin's Lymphoma ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Common Epstein-Barr virus (EBV) type-1 variant strains in both malignant and benign EBV-associated disorders

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1579-1585 ◽  
Author(s):  
V Schuster ◽  
G Ott ◽  
S Seidenspinner ◽  
HW Kreth
Keyword(s):  
Gastric Carcinoma ◽  
Epstein Barr Virus ◽  
Hodgkin's Lymphoma ◽  
Sequence Pattern ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

In the present study, Epstein-Barr virus (EBV) isolates from 18 malignant tumors (angioimmunoblastic lymphadenopathy [AILD], n = 4; Hodgkin's disease [HD], n = 3; pleomorphic T-cell non-Hodgkin's lymphoma [T-NHL], n = 1; B-cell non-Hodgkin's lymphoma [B-NHL], n = 8; gastric carcinoma, n = 2) as well as from 10 tonsils of EBV- seropositive children and from peripheral blood mononuclear cells of 12 children with uncomplicated infectious mononucleosis (IM) and of a boy with severe chronic active EBV infection were genotyped in the EBV nuclear antigen-2 (EBNA-2) gene. A total of 40 of 41 isolates harbored EBV type 1; in 1 specimen (tonsil), only EBV type 2 was found. Further molecular characterization of EBV type-1 wild-type isolates in the EBNA- 2 gene and in the 40-kb distant EBV-encoded small RNAs (EBER) region showed that different groups of stable EBV type-1 variant strains exist in vivo both in benign and malignant lymphatic tissue. Group 1 is composed of EBV type-1 isolates (B-NHL, n = 3; T-NHL, n = 1; HD, n = 1; IM, n = 4) that showed a B95–8-like DNA sequence pattern in both viral genes. Group 2 isolates (HD, n = 1; AILD, n = B-NHL, n = 1; tonsils of EBV-seropositive children, n = 9; IM, n = 20 showed a nucleotide change at position 49095 in the EBNA-2 gene, leading to an amino acid substitution (Pro-->Ser), and EBV type-2 sequences in the EBER region. EBV type-1 isolates that fall into group 3 (AILD, n = 3; HD, n = 1; B- NHL, n = 4; gastric carcinoma, n = 2; IM, n = 6; severe chronic active EBV infection, n = 1) were characterized by typical nucleotide changes and a 3-bp insertion (CTC; extra Leu residue) in the EBNA-2 gene and an EBV type-2-specific sequence pattern in the EBER region. These EBV type- 1 variant strains may represent the most prevalent circulating EBV type- 1 strains in the exposed population and seem not to be restricted to a certain EBV-associated disease or tumor type. However, analysis of more EBV isolates from benign and malignant lesions must show whether more EBV type-1 substrains exist in vivo.

scholarly journals Recent Advances in Diagnostic Approaches for Epstein–Barr Virus

Pathogens ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 226 ◽  
Author(s):  
Mai Abdel Haleem Abusalah ◽  
Siew Hua Gan ◽  
Mohammad A. I. Al-Hatamleh ◽  
Ahmad Adebayo Irekeola ◽  
Rafidah Hanim Shueb ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Epstein Barr Virus ◽  
Antibody Test ◽  
Hodgkin's Lymphoma ◽  
Sample Type ◽  
Barr Virus ◽  
Advantages And Disadvantages ◽  
Negative Results ◽  
Epstein Barr ◽  
The Impact

Epstein–Barr virus (EBV) is the causative agent of many diseases including infectious mononucleosis (IM), and it is associated with different subtypes of lymphoma, sarcoma and carcinoma such as Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. With the advent of improved laboratory tests for EBV, a timelier and accurate diagnosis could be made to aid better prognosis and effective treatment. For histopathological lesions, the in situ hybridization (ISH) of EBV-encoded RNA (EBER) in biopsy tissues remains the gold standard for detecting EBV. Methods such as the heterophile antibody test, immunofluorescence assays, enzyme immunoassays, Western blot, and polymerase chain reaction (PCR) are also employed in the detection of EBV in different types of samples. The determination of EBV viral load using PCR, however, is gaining more prominence in the diagnosis of EBV-associated diseases. Given the challenge of false positive/negative results that are sometimes experienced during the detection of EBV, variability in results from different laboratories, and the impact of factors such as sample type and the immunological status of patients from whom samples are collected, the need to critically examine these present methods is invaluable. This review thus presents current advances in the detection of EBV, detailing the advantages and disadvantages of the various techniques. In addition, fundamental virological concepts are highlighted to enhance the greater understanding, the proper application, and the interpretation of EBV tests.

scholarly journals Epstein-Barr Virus–Negative Hodgkin's Lymphoma After Mycosis Fungoides: Molecular Evidence for Distinct Clonal Origin

2001 ◽  
Vol 14 (2) ◽  
pp. 91-97 ◽  
Author(s):  
Marcus Kremer ◽  
Michael Sandherr ◽  
Birgit Geist ◽  
Antonello D Cabras ◽  
Heinz Höfler ◽  
...  
Keyword(s):  
Mycosis Fungoides ◽  
Hodgkin’S Lymphoma ◽  
Epstein Barr Virus ◽  
Hodgkin's Lymphoma ◽  
Molecular Evidence ◽  
Barr Virus ◽  
Clonal Origin ◽  
Epstein Barr
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