High pretreatment plasma Epstein-Barr virus (EBV) DNA level is a poor prognostic marker in HIV-associated, EBV-negative diffuse large B-cell lymphoma in Malawi.

Nathan D Montgomery,Melissa B Miller,Tamiwe Tomoka,Bongani Kaimila,Robert Krysiak,Avian Elliott,Cara Randall,Dirk P Dittmer,Coxcilly Kampani,Blossom Damania,Fred Chimzimu,Satish Gopal,Takondwa Zuze,Yuri Fedoriw,Maurice Mulenga,Edwards Kasonkanji,Marcia K Sanders,Matthew Painschab,Ryan Seguin

doi:10.1002/cam4.2710

Nathan D Montgomery, Melissa B Miller + Show 17 more

Open Access

PDF Available

https://doi.org/10.1002/cam4.2710

Copy DOI

Export

Save

Cite

Abstract
Highlights/Summary
Full-Text PDF
Similar Papers

Abstract

Listen

Plasma Epstein‐Barr virus (EBV) DNA measurement has established prognostic utility in EBV‐driven lymphomas, where it serves as a circulating tumor DNA marker. The value of plasma EBV measurement may be amplified in sub‐Saharan Africa (SSA), where advanced imaging and molecular technologies for risk stratification are not typically available. However, its utility in diffuse large B‐cell lymphoma (DLBCL) is less certain, given that only a subset of DLBCLs are EBV‐positive. To explore this possibility, we measured plasma EBV DNA at diagnosis in a cohort of patients with DLBCL in Malawi. High plasma EBV DNA at diagnosis (≥3.0 log10 copies/mL) was associated with decreased overall survival (OS) (P = .048). When stratified by HIV status, the prognostic utility of baseline plasma EBV DNA level was restricted to HIV‐positive patients. Unexpectedly, most HIV‐positive patients with high plasma EBV DNA at diagnosis had EBV‐negative lymphomas, as confirmed by multiple methods. Even in these HIV‐positive patients with EBV‐negative DLBCL, high plasma EBV DNA remained associated with shorter OS (P = .014). These results suggest that EBV reactivation in nontumor cells is a poor prognostic finding even in HIV‐positive patients with convincingly EBV‐negative DLBCL, extending the potential utility of EBV measurement as a valuable and implementable prognostic marker in SSA.

Highlights

Epstein‐Barr virus (EBV) is an oncogenic herpesvirus implicated in many lymphomas, as well as some solid tumors.[1]
LMP1 and Epstein‐Barr nuclear antigen 1 (EBNA1) are co‐expressed with Epstein‐Barr encoded RNA (EBER) in EBV's type II and III latency programs, which are typically observed in diffuse large B‐cell lymphoma (DLBCL).[24,25]
Plasma EBV is a promising lymphoma marker in human immunodeficiency virus (HIV)‐positive patients,[28] though its utility has been primarily explored in patients with EBV‐positive tumors

Summary

Introduction

Epstein‐Barr virus (EBV) is an oncogenic herpesvirus implicated in many lymphomas, as well as some solid tumors.[1] For a subset of lymphomas, such as endemic forms of Burkitt lymphoma, EBV is present in the tumor cells of most cases.[2] for other lymphomas, such as diffuse large B‐cell lymphoma (DLBCL), both. | 552 wileyonlinelibrary.com/jou rnal/cam[4]. EBV‐negative and EBV‐positive forms of disease are recognized.[3,4] The likelihood that a patient's DLBCL will be EBV‐associated is primarily related to underlying immune status, with human immunodeficiency virus (HIV) infection, iatrogenic immunosuppression, and advanced age all increasing the likelihood of EBV positivity.[5]. DLBCL is the most common subtype of lymphoma worldwide, and in sub‐Saharan Africa (SSA), the incidence of this and other aggressive B‐cell lymphomas is increasing, primarily due to HIV and population aging.[6,7,8,9] Prior studies have suggested EBV‐positivity in approximately 80%‐90% of cases of HIV‐associated DLBCL with immunoblastic cytology and approximately 30% of cases with centroblastic cytology.[5,10] By comparison, less than 10% of DLBCL arising in HIV‐negative individuals is associated with EBV.[5]

Methods

Results

Conclusion