Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: Correlative analysis from a large North American cooperative group trial

Jennifer A. Kanakry, Hailun Li, Lan L. Gellert, M. Victor Lemas, Wen Son Hsieh, Fangxin Hong, King L. Tan, Randy D. Gascoyne, Leo I. Gordon, Richard I. Fisher, Nancy L. Bartlett, Patrick Stiff, Bruce D. Cheson, Ranjana Advani, Thomas P Miller, Brad S. Kahl, Sandra J. Horning, Richard F. Ambinder

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Abstract

Epstein-Barr virus (EBV) is associated with Hodgkin lymphoma (HL) and can be detected by in situ hybridization (ISH) of viral nucleic acid (EBER) in tumor cells. We sought to determine whether plasma EBV-DNA could serve as a surrogate for EBER-ISH and to explore its prognostic utility in HL. Specimens from the Cancer Cooperative Intergroup Trial E2496 were used to compare pretreatment plasma EBV-DNA quantification with EBV tumor status by EBER-ISH. A cutoff of >60 viral copies/100 μL plasma yielded 96% concordance with EBER-ISH. Pretreatment and month 6 plasma specimens were designated EBV(-) or EBV(+) by this cutoff. Patients with pretreatment EBV(1) plasma (n = 54) had inferior failure-free survival (FFS) compared with those with pretreatment EBV(-) plasma (n = 274), log-rank P = .009. By contrast, no difference in FFS was observed when patients were stratified by EBER-ISH. Pretreatment plasma EBV positivity was an independent predictor of treatment failure on multivariate analyses. At month 6, plasma EBV(+) patients (n = 7) had inferior FFS compared with plasma EBV(-) patients (n = 125), log-rank P = .007. These results confirm that plasma EBV-DNA is highly concordant with EBER-ISH in HL and suggest that it may have prognostic utility both at baseline and after therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003389.

Original languageEnglish (US)
Pages (from-to)3547-3553
Number of pages7
JournalBlood
Volume121
Issue number18
DOIs
StatePublished - May 2 2013

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Human Herpesvirus 4
Hodgkin Disease
Viruses
Plasmas
DNA
In Situ Hybridization
Survival
Tumors
Neoplasms
Treatment Failure
Nucleic Acids
Multivariate Analysis
Cells

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma : Correlative analysis from a large North American cooperative group trial. / Kanakry, Jennifer A.; Li, Hailun; Gellert, Lan L.; Lemas, M. Victor; Hsieh, Wen Son; Hong, Fangxin; Tan, King L.; Gascoyne, Randy D.; Gordon, Leo I.; Fisher, Richard I.; Bartlett, Nancy L.; Stiff, Patrick; Cheson, Bruce D.; Advani, Ranjana; Miller, Thomas P; Kahl, Brad S.; Horning, Sandra J.; Ambinder, Richard F.

In: Blood, Vol. 121, No. 18, 02.05.2013, p. 3547-3553.

Research output: Contribution to journalArticle

Kanakry, JA, Li, H, Gellert, LL, Lemas, MV, Hsieh, WS, Hong, F, Tan, KL, Gascoyne, RD, Gordon, LI, Fisher, RI, Bartlett, NL, Stiff, P, Cheson, BD, Advani, R, Miller, TP, Kahl, BS, Horning, SJ & Ambinder, RF 2013, 'Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: Correlative analysis from a large North American cooperative group trial', Blood, vol. 121, no. 18, pp. 3547-3553. https://doi.org/10.1182/blood-2012-09-454694
Kanakry, Jennifer A. ; Li, Hailun ; Gellert, Lan L. ; Lemas, M. Victor ; Hsieh, Wen Son ; Hong, Fangxin ; Tan, King L. ; Gascoyne, Randy D. ; Gordon, Leo I. ; Fisher, Richard I. ; Bartlett, Nancy L. ; Stiff, Patrick ; Cheson, Bruce D. ; Advani, Ranjana ; Miller, Thomas P ; Kahl, Brad S. ; Horning, Sandra J. ; Ambinder, Richard F. / Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma : Correlative analysis from a large North American cooperative group trial. In: Blood. 2013 ; Vol. 121, No. 18. pp. 3547-3553.
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abstract = "Epstein-Barr virus (EBV) is associated with Hodgkin lymphoma (HL) and can be detected by in situ hybridization (ISH) of viral nucleic acid (EBER) in tumor cells. We sought to determine whether plasma EBV-DNA could serve as a surrogate for EBER-ISH and to explore its prognostic utility in HL. Specimens from the Cancer Cooperative Intergroup Trial E2496 were used to compare pretreatment plasma EBV-DNA quantification with EBV tumor status by EBER-ISH. A cutoff of >60 viral copies/100 μL plasma yielded 96{\%} concordance with EBER-ISH. Pretreatment and month 6 plasma specimens were designated EBV(-) or EBV(+) by this cutoff. Patients with pretreatment EBV(1) plasma (n = 54) had inferior failure-free survival (FFS) compared with those with pretreatment EBV(-) plasma (n = 274), log-rank P = .009. By contrast, no difference in FFS was observed when patients were stratified by EBER-ISH. Pretreatment plasma EBV positivity was an independent predictor of treatment failure on multivariate analyses. At month 6, plasma EBV(+) patients (n = 7) had inferior FFS compared with plasma EBV(-) patients (n = 125), log-rank P = .007. These results confirm that plasma EBV-DNA is highly concordant with EBER-ISH in HL and suggest that it may have prognostic utility both at baseline and after therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003389.",
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AU - Li, Hailun

AU - Gellert, Lan L.

AU - Lemas, M. Victor

AU - Hsieh, Wen Son

AU - Hong, Fangxin

AU - Tan, King L.

AU - Gascoyne, Randy D.

AU - Gordon, Leo I.

AU - Fisher, Richard I.

AU - Bartlett, Nancy L.

AU - Stiff, Patrick

AU - Cheson, Bruce D.

AU - Advani, Ranjana

AU - Miller, Thomas P

AU - Kahl, Brad S.

AU - Horning, Sandra J.

AU - Ambinder, Richard F.

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N2 - Epstein-Barr virus (EBV) is associated with Hodgkin lymphoma (HL) and can be detected by in situ hybridization (ISH) of viral nucleic acid (EBER) in tumor cells. We sought to determine whether plasma EBV-DNA could serve as a surrogate for EBER-ISH and to explore its prognostic utility in HL. Specimens from the Cancer Cooperative Intergroup Trial E2496 were used to compare pretreatment plasma EBV-DNA quantification with EBV tumor status by EBER-ISH. A cutoff of >60 viral copies/100 μL plasma yielded 96% concordance with EBER-ISH. Pretreatment and month 6 plasma specimens were designated EBV(-) or EBV(+) by this cutoff. Patients with pretreatment EBV(1) plasma (n = 54) had inferior failure-free survival (FFS) compared with those with pretreatment EBV(-) plasma (n = 274), log-rank P = .009. By contrast, no difference in FFS was observed when patients were stratified by EBER-ISH. Pretreatment plasma EBV positivity was an independent predictor of treatment failure on multivariate analyses. At month 6, plasma EBV(+) patients (n = 7) had inferior FFS compared with plasma EBV(-) patients (n = 125), log-rank P = .007. These results confirm that plasma EBV-DNA is highly concordant with EBER-ISH in HL and suggest that it may have prognostic utility both at baseline and after therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003389.

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