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

Abstract 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...

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Main Authors: Nathan D. Montgomery, Cara Randall, Matthew Painschab, Ryan Seguin, Bongani Kaimila, Edwards Kasonkanji, Takondwa Zuze, Robert Krysiak, Marcia K. Sanders, Avian Elliott, Melissa B. Miller, Coxcilly Kampani, Fred Chimzimu, Maurice Mulenga, Blossom Damania, Tamiwe Tomoka, Yuri Fedoriw, Dirk P. Dittmer, Satish Gopal
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.2710
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author Nathan D. Montgomery
Cara Randall
Matthew Painschab
Ryan Seguin
Bongani Kaimila
Edwards Kasonkanji
Takondwa Zuze
Robert Krysiak
Marcia K. Sanders
Avian Elliott
Melissa B. Miller
Coxcilly Kampani
Fred Chimzimu
Maurice Mulenga
Blossom Damania
Tamiwe Tomoka
Yuri Fedoriw
Dirk P. Dittmer
Satish Gopal
author_facet Nathan D. Montgomery
Cara Randall
Matthew Painschab
Ryan Seguin
Bongani Kaimila
Edwards Kasonkanji
Takondwa Zuze
Robert Krysiak
Marcia K. Sanders
Avian Elliott
Melissa B. Miller
Coxcilly Kampani
Fred Chimzimu
Maurice Mulenga
Blossom Damania
Tamiwe Tomoka
Yuri Fedoriw
Dirk P. Dittmer
Satish Gopal
author_sort Nathan D. Montgomery
collection DOAJ
description Abstract 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.
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spelling doaj-art-51029e26ebfa45efb3c4f63ab7ca75212025-08-25T10:14:04ZengWileyCancer Medicine2045-76342020-01-019255256110.1002/cam4.2710High pretreatment plasma Epstein‐Barr virus (EBV) DNA level is a poor prognostic marker in HIV‐associated, EBV‐negative diffuse large B‐cell lymphoma in MalawiNathan D. Montgomery0Cara Randall1Matthew Painschab2Ryan Seguin3Bongani Kaimila4Edwards Kasonkanji5Takondwa Zuze6Robert Krysiak7Marcia K. Sanders8Avian Elliott9Melissa B. Miller10Coxcilly Kampani11Fred Chimzimu12Maurice Mulenga13Blossom Damania14Tamiwe Tomoka15Yuri Fedoriw16Dirk P. Dittmer17Satish Gopal18Department of Pathology & Laboratory Medicine University of North Carolina Chapel Hill NC USADepartment of Pathology & Laboratory Medicine University of North Carolina Chapel Hill NC USALineberger Comprehensive Cancer Center University of North Carolina Chapel Hill NC USAUNC Project‐Malawi Lilongwe MalawiUNC Project‐Malawi Lilongwe MalawiUNC Project‐Malawi Lilongwe MalawiUNC Project‐Malawi Lilongwe MalawiUNC Project‐Malawi Lilongwe MalawiLineberger Comprehensive Cancer Center University of North Carolina Chapel Hill NC USAUNC Healthcare Chapel Hill NC USADepartment of Pathology & Laboratory Medicine University of North Carolina Chapel Hill NC USAUNC Project‐Malawi Lilongwe MalawiUNC Project‐Malawi Lilongwe MalawiUNC Project‐Malawi Lilongwe MalawiLineberger Comprehensive Cancer Center University of North Carolina Chapel Hill NC USAUNC Project‐Malawi Lilongwe MalawiDepartment of Pathology & Laboratory Medicine University of North Carolina Chapel Hill NC USALineberger Comprehensive Cancer Center University of North Carolina Chapel Hill NC USALineberger Comprehensive Cancer Center University of North Carolina Chapel Hill NC USAAbstract 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.https://doi.org/10.1002/cam4.2710diffuse large B‐cell lymphomaEpstein‐Barr virusHIVprognosissub‐Saharan Africa
spellingShingle Nathan D. Montgomery
Cara Randall
Matthew Painschab
Ryan Seguin
Bongani Kaimila
Edwards Kasonkanji
Takondwa Zuze
Robert Krysiak
Marcia K. Sanders
Avian Elliott
Melissa B. Miller
Coxcilly Kampani
Fred Chimzimu
Maurice Mulenga
Blossom Damania
Tamiwe Tomoka
Yuri Fedoriw
Dirk P. Dittmer
Satish Gopal
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
Cancer Medicine
diffuse large B‐cell lymphoma
Epstein‐Barr virus
HIV
prognosis
sub‐Saharan Africa
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic diffuse large B‐cell lymphoma
Epstein‐Barr virus
HIV
prognosis
sub‐Saharan Africa
url https://doi.org/10.1002/cam4.2710
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