EBV-Positive Diffuse Large B-Cell Lymphoma of the Elderly

Chapter
Part of the Cancer Growth and Progression book series (CAGP, volume 14)

Abstract

The purpose of this chapter is to provide a thorough summary of the existing knowledge of EBV-positive DLBCL of the elderly. We will discuss the pathogenesis behind EBV-driven malignant transformation of B-cells, the different EBV latency patterns associated with DLBCL, the distinct pathological characteristics of EBV-positive DLBCL, the differential diagnosis of EBV-positive DLBCL, the clinical characteristics of patients with EBV-positive DLBCL of the elderly, the potential predictive and prognostic value of EBV tumoral status in patients with DLBCL, and potential strategies for the treatment of this rare entity.

Keywords

Hodgkin Lymphoma Overall Response Rate Primary Effusion Lymphoma DLBCL Patient Classical Hodgkin Lymphoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Dr. Castillo would like to thank Dr. Roberto N. Miranda from the Division of Hematopathology at MD Anderson Cancer Center in Houston, Texas for providing the pathological images included in this chapter.

References

  1. Alizadeh AA, Eisen MB et al (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403(6769):503–511PubMedCrossRefGoogle Scholar
  2. Brimo F, Michel RP et al (2007) Primary effusion lymphoma: a series of 4 cases and review of the literature with emphasis on cytomorphologic and immunocytochemical differential diagnosis. Cancer 111(4):224–233PubMedCrossRefGoogle Scholar
  3. Castillo J, Pantanowitz L et al (2008) HIV-associated plasmablastic lymphoma: lessons learned from 112 published cases. Am J Hematol 83(10):804–809PubMedCrossRefGoogle Scholar
  4. Chang KC, Chen PC et al (2008) Changing patterns in the frequency of Hodgkin lymphoma subtypes and Epstein-Barr virus association in Taiwan. Cancer Sci 99(2):345–349PubMedCrossRefGoogle Scholar
  5. ClinicalTrials.gov. Bortezomib and Ganciclovir in treating patients with relapsed or refractory Epstein Barr virus-positive lymphoma. Available at http://clinicaltrials.gov/ct2/show/NCT00093704. Accessed 30 Aug 2010
  6. ClinicalTrials.gov. Epstein-Barr Virus (EBV)-specific T cells as therapy for relapsed/refractory EBV-positive lymphomas. Available at http://clinicaltrials.gov/ct2/show/NCT00779337. Accessed 30 Aug 2010
  7. ClinicalTrials.gov. Safety study of EBV specific cytotoxic T-cells to treat relapsed EBV-positive lymphoma. Available at http://clinicaltrials.gov/ct2/show/NCT00058617. Accessed 30 Aug 2010
  8. ClinicalTrials.gov. Study of arginine butyrate and ganciclovir/valganciclovir in EBV(+) lymphoid malignancies. Available at http://clinicaltrials.gov/ct2/show/NCT00917826. Accessed 30 Aug 2010
  9. DLBCL (1993) A predictive model for aggressive non-Hodgkin’s lymphoma. The international non-Hodgkin’s lymphoma prognostic factors project. N Engl J Med 329(14):987–994Google Scholar
  10. Fagnoni FF, Vescovini R et al (2000) Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. Blood 95(9):2860–2868PubMedGoogle Scholar
  11. Feugier P, Van Hoof A et al (2005) 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(18):4117–4126PubMedCrossRefGoogle Scholar
  12. Franceschi C, Capri M et al (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128(1):92–105PubMedCrossRefGoogle Scholar
  13. Gibson SE, Hsi ED (2009) 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(5):653–661PubMedCrossRefGoogle Scholar
  14. Glaser SL, Lin RJ et al (1997) Epstein-Barr virus-associated Hodgkin’s disease: epidemiologic characteristics in international data. Int J Cancer 70(4):375–382PubMedCrossRefGoogle Scholar
  15. Habermann TM, Weller EA et al (2006) Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 24(19):3121–3127PubMedCrossRefGoogle Scholar
  16. Hans CP, Weisenburger DD et al (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103(1):275–282PubMedCrossRefGoogle Scholar
  17. Heslop HE, Slobod KS et al (2010) Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood 115(5):925–935PubMedCrossRefGoogle Scholar
  18. Hoeller S, Tzankov A et al (2010) Epstein-Barr virus-positive diffuse large B-cell lymphoma in elderly patients is rare in Western populations. Hum Pathol 41(3):352–357PubMedCrossRefGoogle Scholar
  19. Holtan SG, Porrata LF et al (2008) mTOR inhibitor monotherapy is insufficient to suppress viremia and disease progression in Epstein-Barr virus-driven lymphoproliferative disorders (EBV-LPD). Am J Hematol 83(8):688–689PubMedCrossRefGoogle Scholar
  20. Jones K, Nourse J et al (2010) Sodium valproate in combination with ganciclovir induces lysis of EBV-infected lymphoma cells without impairing EBV-specific T-cell immunity. Int J Lab Hematol 32(1 Pt 1):e169–e174PubMedCrossRefGoogle Scholar
  21. Knecht H, Berger C et al (2001) The role of Epstein-Barr virus in neoplastic transformation. Oncology 60(4):289–302PubMedCrossRefGoogle Scholar
  22. Koch S, Larbi A et al (2008) Multiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people. Immun Ageing 5:6PubMedCrossRefGoogle Scholar
  23. Kuze T, Nakamura N et al (2000) 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(12):1233–1240PubMedCrossRefGoogle Scholar
  24. Morales D, Beltran B et al (2010) Epstein-Barr virus as a prognostic factor in de novo nodal diffuse large B-cell lymphoma. Leuk Lymphoma 51(1):66–72PubMedCrossRefGoogle Scholar
  25. Nakamura S, Jaffe E et al (2008) EBV positive diffuse large B-cell of the elderly. In: Swerdlow S, Campo E, Harris N et al (eds) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon, pp 243–244Google Scholar
  26. Naylor K, Li G et al (2005) The influence of age on T cell generation and TCR diversity. J Immunol 174(11):7446–7452PubMedGoogle Scholar
  27. Oyama T, Ichimura K et al (2003) Senile EBV+  B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol 27(1):16–26PubMedCrossRefGoogle Scholar
  28. Oyama T, Yamamoto K et al (2007) Age-related EBV-associated B-cell lymphoproliferative disorders constitute a distinct clinicopathologic group: a study of 96 patients. Clin Cancer Res 13(17):5124–5132PubMedCrossRefGoogle Scholar
  29. Park S, Lee J et al (2007) The impact of Epstein-Barr virus status on clinical outcome in diffuse large B-cell lymphoma. Blood 110(3):972–978PubMedCrossRefGoogle Scholar
  30. Perrine SP, Hermine O et al (2007) A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood 109(6):2571–2578PubMedCrossRefGoogle Scholar
  31. Pfreundschuh M, Trumper L et al (2006) CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 7(5):379–391PubMedCrossRefGoogle Scholar
  32. Rosenwald A, Wright G et al (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346(25):1937–1947PubMedCrossRefGoogle Scholar
  33. Shimoyama Y, Asano N et al (2009) Age-related EBV-associated B-cell lymphoproliferative disorders: diagnostic approach to a newly recognized clinicopathological entity. Pathol Int 59(12):835–843PubMedCrossRefGoogle Scholar
  34. Spaulding C, Guo W et al (1999) Resistance to apoptosis in human CD8+ T cells that reach replicative senescence after multiple rounds of antigen-specific proliferation. Exp Gerontol 34(5):633–644PubMedCrossRefGoogle Scholar
  35. Tan LH (2009) A practical approach to the understanding and diagnosis of lymphoma: an assessment of the WHO classification based on immunoarchitecture and immuno-ontogenic principles. Pathology 41(4):305–326PubMedCrossRefGoogle Scholar
  36. Thompson MP, Kurzrock R (2004) Epstein-Barr virus and cancer. Clin Cancer Res 10(3):803–821PubMedCrossRefGoogle Scholar
  37. Vaysberg M, Balatoni CE et al (2007) Rapamycin inhibits proliferation of Epstein-Barr virus-positive B-cell lymphomas through modulation of cell-cycle protein expression. Transplantation 83(8):1114–1121PubMedCrossRefGoogle Scholar
  38. Wong HH, Wang J (2009) Epstein-Barr virus positive diffuse large B-cell lymphoma of the elderly. Leuk Lymphoma 50(3):335–340PubMedCrossRefGoogle Scholar
  39. Yoshino T, Nakamura S et al (2006) Epstein-Barr virus involvement is a predictive factor for the resistance to chemoradiotherapy of gastric diffuse large B-cell lymphoma. Cancer Sci 97(2):163–166PubMedCrossRefGoogle Scholar
  40. Zinkernagel RM, Moskophidis D et al (1993) Effector T-cell induction and T-cell memory versus peripheral deletion of T cells. Immunol Rev 133:199–223PubMedCrossRefGoogle Scholar
  41. Zou P, Kawada J et al (2007) Bortezomib induces apoptosis of Epstein-Barr virus (EBV)-transformed B cells and prolongs survival of mice inoculated with EBV-transformed B cells. J Virol 81(18):10029–10036PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.The Warren Alpert Medical School of Brown UniversityProvidenceUSA
  2. 2.Division of Hematology and OncologyThe Miriam HospitalProvidenceUSA

Personalised recommendations