Outcomes among North American patients with diffuse large B-cell lymphoma are independent of tumor Epstein-Barr virus positivity or immunosuppression

Abstract

The prevalence, presenting clinical and pathological characteristics, and outcomes for patients with diffuse large B-cell lymphoma that is Epstein-Barr virus positive remain uncertain as does the impact of congenital or iatrogenic immunosuppression. Patients with newly diagnosed diffuse large B-cell lymphoma with available tissue arrays were identified from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource. Patients infected with human immunodeficiency virus or who had undergone a prior organ transplant were excluded. Epstein-Barr virus-associated ribonucleic acid testing was performed on all tissue arrays. A history of significant congenital or iatrogenic immunosuppression was determined for all patients. At enrollment, 16 of the 362 (4.4%) biopsies were positive for Epstein-Barr virus. Thirty-nine (10.8%) patients had a significant history of immunosuppression. Patients with Epstein-Barr-positive diffuse large B-cell lymphoma had no unique clinical characteristics but on pathology exhibited a higher frequency of CD30 positivity (25.0% versus 8.1%, respectively; P<0.01), and non-germinal-center subtype (62.5% versus 34.1%, respectively; P<0.01). No baseline clinical characteristics were associated with a history of immunosuppression. With a median follow up of 59 months, and after adjustment for International Prognostic Index, there was no association of Epstein-Barr virus positivity or immunosuppression with event-free survival at 24 months (odds ratio=0.49; 95% confidence interval: 0.13–1.84 and odds ratio=0.81; 95% confidence interval: 0.37–1.77) or overall survival (hazard ratio=0.86; 95% confidence interval: 0.38–1.97 and hazard ratio=1.00; 95% confidence interval: 0.57–1.74). In contrast to non-Western populations, our North American population had a low prevalence of Epstein-Barr virus-positive diffuse large B-cell lymphoma that did not convey an adverse prognosis. A history of immunosuppression, while known to be a risk factor for the development of diffuse large B-cell lymphoma, did not affect subsequent prognosis.

Clinical characteristics and prognostic significance of EBER positivity in diffuse large B-cell lymphoma: A meta-analysis

“…The incidence of EBER positivity in these studies ranged from 1.4% to 14.9%. Ten studies were from Asian countries [ 10 , 11 , 15 – 20 , 22 , 24 ], two from Caucasian countries [ 14 , 23 ], and one from Peru [ 21 ]. The HRs with 95% CIs were directly extracted in 9 original studies [ 11 , 14 , 15 , 18 – 20 , 22 – 24 ].…”

The tumour microenvironment is immuno‐tolerogenic and a principal determinant of patient outcome in EBV‐positive diffuse large B‐cell lymphoma

“…The differences in the TME between patients have not been accounted for in previous studies and may explain why the inferior survival in patients with EBV -pos DLBCL treated by R-CHOP has been demonstrated in some studies but not confirmed in all. [4][5][6][7][8][9] Application of NanoString™ enabled genes reflective of the TME to be simultaneously interrogated along with EBV-tissue status. Intratumoral T-cell infiltration has previously been shown to be prognostic in DLBCL treated with R-CHOP.…”

“…Results of large population-based series that have formally examined the impact of EBV-tissue status in patients with de novo DLBCL treated with frontline R-CHOP immuno-chemotherapy have been conflicting. [5][6][7]35 It remains unclear to what extent these differences reflect ethnic variations between studies conducted in either predominantly Asian or Caucasian population, and further large-scale studies in new geographic localities are required. However, addition of rituximab to CHOP ("R-CHOP") improves response and survival.…”

“…[1][2][3] In some studies, but not in others, it has been associated with poor outcome with standard "R-CHOP" (rituximab-cyclophosphamide/doxorubicin/vincristine/ prednisolone) immuno-chemotherapy. [4][5][6][7][8][9] Recent studies indicate EBV -pos DLBCL occurs in both younger and older patients and that age does not influence pathological characteristics. 4,10 Epstein-Barr virus represents a foreign antigen against which healthy EBV-specific cytotoxic T-cell (CTL) immunity has been extensively characterised.…”

EBV positive DLBCL, NOS

“…In contrast to non-Western populations, the North American population had a low prevalence of EBV+ DLBCL that did not convey an adverse prognosis. A history of immunosuppression, while known to be a risk factor for the development of diffuse large B-cell lymphoma, did not affect subsequent prognosis (Tracy SI et al, 2018).…”