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      Clinical outcome of Epstein–Barr virus-positive diffuse large B-cell lymphoma of the elderly in the rituximab era

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          Abstract

          Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma. The incidence of Epstein–Barr virus (EBV)-positive DLBCL in Asian and Latin American countries ranges from 8 to 10%. The prognosis of patients with EBV-positive DLBCL is controversial. To compare the clinical outcome of EBV-positive and EBV-negative patients with DLBCL in the rituximab era, we analyzed 239 patients with de novo DLBCL diagnosed between January 2007 and December 2011. The presence of EBV in lymphoma cells was detected using EBV-encoded RNA in situ hybridization, and it was found that 18 (6.9%) of 260 patients with diagnosed DLBCL tested positive. Among the 260 cases, 216 cases were treated with rituximab plus chemotherapy, as were 8 EBV-positive DLBCL patients. The median overall survival and progression-free survival times in patients with EBV-positive DLBCL were 8.7 months and 6.8 months, respectively. The median overall survival and progression-free survival could not be determined in EBV-negative DLBCL patients ( P = 0.0002 , P < 0.0001, respectively). The outcome of patients with EBV-positive DLBCL remains poor, even in the rituximab era.

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          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.

          Bertrand Coiffier, Catherine Thieblemont, Eric Van Den Neste … (2010)
          We report the outcome of patients included in the LNH-98.5 study, which compared cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to rituximab plus CHOP (R-CHOP) therapy in 399 patients with diffuse large B-cell lymphoma (DLBCL) aged 60 to 80 years, with a median follow-up time of 10 years. Clinical event information was updated in all living patients (with the exception of 3 patients) in 2009. Survival end points were improved in patients treated with R-CHOP: the 10-year progression-free survival was 36.5%, compared with 20% with CHOP alone, and the 10-year overall survival was 43.5% compared with 27.6%. The same risk of death due to other diseases, secondary cancers, and late relapses was observed in both study arms. Relapses occurring after 5 years represented 7% of all disease progressions. The results from the 10-year analysis confirm the benefits and tolerability of the addition of rituximab to CHOP. Our findings underscore the need to treat elderly patients as young patients, with the use of curative chemotherapy.
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            Progress and problems in understanding and managing primary Epstein-Barr virus infections.

            Oludare A Odumade, Henry Balfour, Oludare Odumade (2011)
            Epstein-Barr virus (EBV) is a gammaherpesvirus that infects a large fraction of the human population. Primary infection is often asymptomatic but results in lifelong infection, which is kept in check by the host immune system. In some cases, primary infection can result in infectious mononucleosis. Furthermore, when host-virus balance is not achieved, the virus can drive potentially lethal lymphoproliferation and lymphomagenesis. In this review, we describe the biology of EBV and the host immune response. We review the diagnosis of EBV infection and discuss the characteristics and pathogenesis of infectious mononucleosis. These topics are approached in the context of developing therapeutic and preventative strategies.
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              Age-related EBV-associated B-cell lymphoproliferative disorders constitute a distinct clinicopathologic group: a study of 96 patients.

              Takashi Oyama, Kazuhito Yamamoto, Naoko Asano … (2007)
              We have recently reported EBV+ B-cell lymphoproliferative disorders (LPD) occurring predominantly in elderly patients, which shared features of EBV+ B-cell neoplasms arising in the immunologically deteriorated patients despite no predisposing immunodeficiency and were named as senile or age-related EBV+ B-cell LPDs. To further characterize this disease, age-related EBV+ B-cell LPDs were compared with EBV-negative diffuse large B-cell lymphomas (DLBCL). Among 1,792 large B-cell LPD cases, 96 EBV+ cases with available clinical data set were enrolled for the present study. For the control group, 107 patients aged over 40 years with EBV-negative DLBCL were selected. We compared clinicopathologic data between two groups and determined prognostic factors by univariate and multivariate analysis. Patients with age-related EBV+ B-cell LPDs showed a higher age distribution and aggressive clinical features or parameters than EBV-negative DLBCLs: 44% with performance status >1, 58% with serum lactate dehydrogenase level higher than normal, 49% with B symptoms, and higher involvement of skin and lung. Overall survival was thus significantly inferior in age-related EBV+ group than in DLBCLs. Univariate and multivariate analyses further identified two factors, B symptoms and age older than 70 years, independently predictive for survival. A prognostic model using these two variables well defined three risk groups: low risk (no adverse factors), intermediate risk (one factor), and high risk (two factors). These findings suggest that age-related EBV+ B-cell LPDs constitute a distinct group, and innovative therapeutic strategies such as EBV-targeted T-cell therapy should be developed for this uncommon disease.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancer Sci
                Journal ID (iso-abbrev): Cancer Sci
                Journal ID (publisher-id): cas
                Title: Cancer Science
                Publisher: BlackWell Publishing Ltd (Oxford, UK )
                ISSN (Print): 1347-9032
                ISSN (Electronic): 1349-7006
                Publication date (Print): September 2014
                Publication date (Electronic): 08 September 2014
                Volume: 105
                Issue: 9
                Pages: 1170-1175
                Affiliations
                [1 ]Department of Hematology–Oncology, School of Medicine, Tokai University Isehara, Japan
                [2 ]Department of Pathology, School of Medicine, Tokai University Isehara, Japan
                [3 ]Department of Hematology, Ozawa Hospital Odawara, Japan
                [4 ]Department of Hematology, Ebina General Hospital Ebina, Japan
                [5 ]Department of Hematology, Red Cross Hadano Hospital Hadano, Japan
                [6 ]Department of Hematology, Atsugi Satoh Hospital Atsugi, Japan
                Author notes
                Correspondence Ai Sato, Department of Hematology–Oncology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan., Tel: +81-463-93-1121; Fax: +81-463-92-4511;, E-mail: mogumogu@ 123456is.icc.u-tokai.ac.jp

                Funding information Tokai University.

                Article
                DOI: 10.1111/cas.12467
                PMC ID: 4462402
                PubMed ID: 24974976
                SO-VID: 5b9ebede-9c36-4ae9-8b84-7cd0931cc3b1
                Copyright © © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
                License:

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 10 February 2014
                Date revision received : 06 June 2014
                Date accepted : 13 June 2014
                Categories
                Subject: Original Articles

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: diffuse large b-cell lymphoma,epstein–barr virus (ebv),prognosis
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: diffuse large b-cell lymphoma, epstein–barr virus (ebv), prognosis

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