Epstein-Barr virus positive diffuse large B-cell lymphoma predict poor outcome, regardless of the age

Ting-Xun Lu, Jin-Hua Liang, Yi Miao, Lei Fan, Li Wang, Xiao-Yan Qu, Lei Cao, Qi-Xing Gong, Zhen Wang, Zhi-Hong Zhang, Wei Xu, Jian-Yong Li, Ting-Xun Lu, Jin-Hua Liang, Yi Miao, Lei Fan, Li Wang, Xiao-Yan Qu, Lei Cao, Qi-Xing Gong, Zhen Wang, Zhi-Hong Zhang, Wei Xu, Jian-Yong Li

Abstract

Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly is defined as patients older than 50 years alone. However, recent studies showed young patients with sound immune status could also be affected. In this study, we investigated the clinical features and outcomes of patients with EBV positive DLBCL in the different age groups using different EBER cut-off values. The prevalence of EBV positive DLBCL was 14.0% (35/250) and 10.4% (26/250) for EBER cut-off of 20% and 50%, respectively. With both EBER cut-off values, patients with EBV DLBCL shared many unfavorable prognostic characteristics, regardless of age. EBV positive patients, both in the elderly and young groups, showed significantly worse overall survival and progression-free survival than negative cases. Moreover, no significant differences of outcomes were identified between different age groups with EBV positive DLBCL. In conclusion, EBV positive DLBCL patients, regardless of age, shared similar poor prognostic features and showed worse outcome than negative cases. We suggest that the age criterion of EBV positive DLBCL of the elderly, and possibly the name itself, be modified in future.

Figures

Figure 1. The overall survival and progession-free…
Figure 1. The overall survival and progession-free survival of the whole cohort.
The EBV positive patients had significantly worse OS (a,c) and PFS (b,d) than the negative ones with both EBER cut-off values. Abbreviations: EBER: Epstein-Barr virus-encoded RNA; EBV: Epstein-Barr virus; OS: overall survival; PFS: progression-free survival.
Figure 2. The survival differences of elderly…
Figure 2. The survival differences of elderly DLBCL with EBV status.
The EBV positive patients of the elderly group showed significantly worse OS (a,c) and PFS (b,d) than negative ones, regardless of the EBER cut-off values. Abbreviations: EBER: Epstein-Barr virus-encoded RNA; EBV: Epstein-Barr virus; OS: overall survival; PFS: progression-free survival.
Figure 3. The survival differences of young…
Figure 3. The survival differences of young DLBCL with EBV status.
The EBV positive patients of the young group showed significantly worse OS (a,c) and PFS (b,d) than negative ones, regardless of the EBER cut-off values. Abbreviations: EBER: Epstein-Barr virus-encoded RNA; EBV: Epstein-Barr virus; OS: overall survival; PFS: progression-free survival.
Figure 4. The survival differences of EBV…
Figure 4. The survival differences of EBV positive DLBCL beween different age groups.
The EBV positive DLBCL of the elderly group showed similar OS (a,c) and PFS (b,d) with the young ones, regardless of the EBER cut-off values. Abbreviations: EBER: Epstein-Barr virus-encoded RNA; EBV: Epstein-Barr virus; OS: overall survival; PFS: progression-free survival.

References

    1. Jaffe E. S. & Pittaluga S. Aggressive B-cell lymphomas: a review of new and old entities in the WHO classification. Hematology Am Soc Hematol Educ Program 2011, 506–514 (2011).
    1. Campo E. et al. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood 117, 5019–5032 (2011).
    1. Swerdlow S. H. et al. WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC, (2008).
    1. Park S. et al. The impact of Epstein-Barr virus status on clinical outcome in diffuse large B-cell lymphoma. Blood 110, 972–978 (2007).
    1. Oyama T. et al. Age-related EBV-associated B-cell lymphoproliferative disorders constitute a distinct clinicopathologic group: a study of 96 patients. Clin Cancer Res 13, 5124–5132 (2007).
    1. Kuze T. et al. The characteristics of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma: comparison between EBV(+) and EBV(−) cases in Japanese population. Jpn J Cancer Res 91, 1233–1240 (2000).
    1. Ok C. Y. et al. Prevalence and clinical implications of epstein-barr virus infection in de novo diffuse large B-cell lymphoma in Western countries. Clin Cancer Res 20, 2338–2349 (2014).
    1. Gibson S. E. & Hsi E. D. Epstein-Barr virus-positive B-cell lymphoma of the elderly at a United States tertiary medical center: an uncommon aggressive lymphoma with a nongerminal center B-cell phenotype. Hum Pathol 40, 653–661 (2009).
    1. Coiffier B. et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood 116, 2040–2045 (2010).
    1. Feugier P. et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 23, 4117–4126 (2005).
    1. Ahn J. S. et al. Clinical outcome of elderly patients with Epstein-Barr virus positive diffuse large B-cell lymphoma treated with a combination of rituximab and CHOP chemotherapy. Am J Hematol 88, 774–779 (2013).
    1. Morales D. et al. Epstein-Barr virus as a prognostic factor in de novo nodal diffuse large B-cell lymphoma. Leuk Lymphoma 51, 66–72 (2010).
    1. Sato A. et al. Clinical outcome of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly in the rituximab era. Cancer Sci 105, 1170–1175 (2014).
    1. Hong J. Y. et al. EBV-positive diffuse large B-cell lymphoma in young adults: is this a distinct disease entity? Ann Oncol 26, 548–555 (2014).
    1. Montes-Moreno S. et al. EBV-positive diffuse large B-cell lymphoma of the elderly is an aggressive post-germinal center B-cell neoplasm characterized by prominent nuclear factor-kB activation. Mod Pathol 25, 968–982 (2012).
    1. Beltran B. E. et al. EBV-positive diffuse large b-cell lymphoma in young immunocompetent individuals. Clin Lymphoma Myeloma Leuk 11, 512–516 (2011).
    1. Cohen M. et al. Epstein-Barr virus-positive diffuse large B-cell lymphoma association is not only restricted to elderly patients. Int J Cancer 135, 2816–2824 (2014).
    1. Hofscheier A. et al. Geographic variation in the prevalence of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly: a comparative analysis of a Mexican and a German population. Mod Pathol 24, 1046–1054 (2011).
    1. Castillo J. J. et al. Epstein-barr virus-positive diffuse large B-cell lymphoma of the elderly: what we know so far. Oncologist 16, 87–96 (2011).
    1. Ok C. Y. et al. EBV-positive diffuse large B-cell lymphoma of the elderly. Blood 122, 328–340 (2013).
    1. Visco C. et al. Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Leukemia 26, 2103–2113 (2012).
    1. Meyer P. N. et al. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab. J Clin Oncol 29, 200–207 (2011).
    1. Choi W. W. et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res 15, 5494–5502 (2009).
    1. Hans C. P. et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103, 275–282 (2004).
    1. Cheson B. D. et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32, 3059–3068 (2014).
    1. Beltran B. E. et al. EBV-positive diffuse large B-cell lymphoma of the elderly: a case series from Peru. Am J Hematol 86, 663–667 (2011).
    1. Adams H. J. et al. False-negative FDG-PET in histologically proven extensive large cell bone marrow involvement in diffuse large B-cell lymphoma. Am J Hematol 90, 10.1002/ajh.23986 (2015).
    1. Troppan K. T. et al. C-reactive protein level is a prognostic indicator for survival and improves the predictive ability of the R-IPI score in diffuse large B-cell lymphoma patients. Br J Cancer 111, 55–60 (2014).
    1. Tisi M. C. et al. Anemia in diffuse large B-cell non-Hodgkin lymphoma: the role of interleukin-6, hepcidin and erythropoietin. Leuk Lymphoma 55, 270–275 (2014).
    1. Duletic-Nacinovic A. et al. Serum IL-6, IL-8, IL-10 and beta2-microglobulin in association with International Prognostic Index in diffuse large B cell lymphoma. Tumori 94, 511–517 (2008).
    1. Vlasveld L. T. et al. Elevated serum CA-125 concentrations due to expression by a diffuse large B-cell lymphoma. Ann Clin Biochem 37 (Pt 4), 545–548 (2000).
    1. Nicolaides C. et al. Diffuse large cell lymphomas: identification of prognostic factors and validation of the International Non-Hodgkin’s Lymphoma Prognostic Index. A Hellenic Cooperative Oncology Group Study. Oncology 55, 405–415 (1998).
    1. Coutinho R. et al. Poor concordance among nine immunohistochemistry classifiers of cell-of-origin for diffuse large B-cell lymphoma: implications for therapeutic strategies. Clin Cancer Res 19, 6686–6695 (2013).
    1. Hu S. et al. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program. Blood 121, 4021–4031 (2013).
    1. Yoon D. H. et al. Ki-67 expression as a prognostic factor in diffuse large B-cell lymphoma patients treated with rituximab plus CHOP. Eur J Haematol 85, 149–157 (2010).
    1. Miyazaki K. et al. CD5-positive diffuse large B-cell lymphoma: a retrospective study in 337 patients treated by chemotherapy with or without rituximab. Ann Oncol 22, 1601–1607 (2011).
    1. Slack G. W. et al. CD30 expression in de novo diffuse large B-cell lymphoma: a population-based study from British Columbia. Br J Haematol 167, 608–617 (2014).
    1. Hu S. et al. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Blood 121, 2715–2724 (2013).
    1. Martin-Perez D. et al. Epstein-Barr virus microRNAs repress BCL6 expression in diffuse large B-cell lymphoma. Leukemia 26, 180–183 (2012).
    1. Wong H. H., Wang J. Epstein-Barr virus positive diffuse large B-cell lymphoma of the elderly. Leuk Lymphoma 50, 335–340 (2009).
    1. Vockerodt M. et al. The Epstein-Barr virus and the pathogenesis of lymphoma. J Pathol 235, 312–322 (2015).
    1. Zelenetz. A. D. et al. NCCN Clinical Practice Guidelines in Oncology. Non-Hodgkin’s Lymphomas. Version 1, 160–161 (2015).
    1. Andrade T. A. et al. A microRNA signature profile in EBV+ diffuse large B-cell lymphoma of the elderly. Oncotarget 5, 11813–11826 (2014).
    1. Ozsan N. et al. Epstein-Barr virus (EBV) positive diffuse large B cell lymphoma of the elderly-experience of a single center from Turkey. Pathol Res Pract 209, 471–478 (2013).
    1. Morscio J. et al. Gene expression profiling reveals clear differences between EBV-positive and EBV-negative posttransplant lymphoproliferative disorders. Am J Transplant 13, 1305–1316 (2013).
    1. Wada N. et al. Epstein-barr virus in diffuse large B-Cell lymphoma in immunocompetent patients in Japan is as low as in Western Countries. J Med Virol 83, 317–321 (2011).
    1. Kato H. et al. Gene expression profiling of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways. Cancer Sci 105, 537–544 (2014).
    1. De Unamuno Bustos B. et al. Epstein-Barr virus-positive diffuse large B-cell lymphoma in an elderly patient. Clin Exp Dermatol 39, 484–487 (2014).
    1. Scuto A. et al. STAT3 inhibition is a therapeutic strategy for ABC-like diffuse large B-cell lymphoma. Cancer Res 71, 3182–3188 (2011).
    1. Lam L. T. et al. Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-{kappa}B pathways in subtypes of diffuse large B-cell lymphoma. Blood 111, 3701–3713 (2008).
    1. Lei T. et al. Targeting of DICE1 tumor suppressor by Epstein-Barr virus-encoded miR-BART3* microRNA in nasopharyngeal carcinoma. Int J Cancer 133, 79–87 (2013).
    1. Jansson M. D. & Lund A. H. MicroRNA and cancer. Mol Oncol 6, 590–610 (2012).

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