Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma in the Elderly: A Matched Case-Control Analysis

PLoS One. 2015 Jul 29;10(7):e0133973. doi: 10.1371/journal.pone.0133973. eCollection 2015.

Abstract

Background: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) in the elderly has rarely been reported. This study aimed to explore the clinical characteristics and prognosis of this entity.

Methods: In situ hybridization (ISH) analysis of Epstein-Barr virus (EBV) and immunohistochemistry was performed in 230 tumor specimens from consecutive de novo DLBCL patients over 50 years old. A matched-case control analysis (1:3) was utilized to compare EBV-positive and EBV-negative DLBCL in the elderly.

Results: A total of 16 patients (7.0%) were diagnosed with EBV-positive DLBCL. Of these 16 cases, the median age was 62 years, with a male to female ratio of 11:5. Elderly EBV-positive DLBCL patients had a higher incidence of non-germinal center B-cell (non-GCB) subtypes (87.5%) and high Ki67 (75%) and CD30 expression (93.8%). For EBV-positive patients undergoing initial chemotherapy, 7 of 16 (43.8%) had complete remission, 2 (12.5%) had partial remission, 2 (12.5%) had stable disease, and 5 (31.3%) had progressive disease. The median overall survival was 9 months for the EBV-positive patients. A matched-case control analysis suggested that EBV-positive patients had inferior survival outcomes compared with EBV-negative patients (3-year progression-free survival [PFS]: 25% vs. 76.7%, respectively; 3-year overall survival [OS]: 25% vs. 77.4%, respectively; P<0.001).

Conclusion: EBV-positive DLBCL of the elderly is associated with an inferior clinical course and inferior survival outcomes. The role of EBV in this disease and the optimal management of this subgroup warrants further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Case-Control Studies
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Etoposide / therapeutic use
  • Female
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Large B-Cell, Diffuse / virology*
  • Male
  • Middle Aged
  • Prednisone / therapeutic use
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Vincristine / therapeutic use

Substances

  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol
  • EPOCH protocol

Grants and funding

This work was supported by the National Natural Science Foundation of China (project number: 81472759, 81301903), Guangdong Natural Science Foundation (project number: S2013010016331), Science and Technology Planning Project of Guangdong Province, China (project number: 2014J4100163), Science and Technology Planning Project of Guangzhou, China (project number: 2013B021800142), Fundamental Research Funds for the Central Universities (project number: 10ykpy36), and Research Award Funds for Outstanding Young Researchers in Sun Yat-Sen Cancer Center.