Detection of free circulating Epstein-Barr virus DNA in plasma of patients with Hodgkin’s disease

Musacchio, Juliane; Carvalho, Maria da Glória da Costa; Morais, José Carlos; Silva, Nathalie Henriques; Scheliga, Adriana; Romano, Sérgio; Spector, Nelson

doi:10.1590/s1516-31802006000300009

Cited by 21 publications

(24 citation statements)

References 15 publications

(14 reference statements)

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“…8 Others have reported an association between detectable plasma EBV-DNA and higher stage disease. 10 A recent study of patients with newly diagnosed or relapsed HL found pretreatment plasma EBV-DNA to be associated with EBV status by EBER-ISH and noted that plasma EBV-DNA levels declined with treatment. 11 Herein, we examine the relationship in HL between plasma EBV-DNA measurement and EBV tumor status and explore the utility of plasma EBV-DNA as a prognostic marker at diagnosis and 6-month follow-up.…”

Section: Epstein-barr Virus (Ebv) Is a Gammaherpesvirus Present Inmentioning

confidence: 99%

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

Kanakry

Gellert

et al. 2013

Blood

117

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• Plasma EBV-DNA is highly concordant with EBV tumor status in Hodgkin lymphoma.• Plasma EBV-DNA has prognostic significance in Hodgkin lymphoma, both before therapy and at month 6 of follow-up.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 mL plasma yielded 96% concordance with EBER-ISH. Pretreatment and month 6 plasma specimens were designated EBV(-) or EBV(1) by this cutoff. Patients with pretreatment EBV(1) plasma (n 5 54) had inferior failure-free survival (FFS) compared with those with pretreatment EBV(-) plasma (n 5 274), log-rank P 5 .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(1) patients (n 5 7) had inferior FFS compared with plasma EBV(-) patients (n 5 125), log-rank P 5 .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. (Blood. 2013;121(18):3547-3553)

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Section: Epstein-barr Virus (Ebv) Is a Gammaherpesvirus Present Inmentioning

confidence: 99%

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

Kanakry

Gellert

et al. 2013

Blood

117

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“…Their real-time quantitative PCR resulted in a lower overall positivity rate: 69% (18/26) samples from EBV-positive HL and 10% (2/20) samples from EBV-negative cases were positive. Using conventional PCR, Musacchio et al [3] observed similar results: 91% (10/11) of EBV-positive HL patients were EBV-DNA-positive in plasma, and 16% (3/19) of cases without LMP1 had detectable free circulating EBV-DNA.…”

mentioning

confidence: 71%

“…Latent EBV genomes are found in the malignant Reed-Sternberg/Hodgkin cells in approximately 30-50% of patients with HL in Western countries. Several studies have reported presence of EBV-DNA in the blood of patients with EBV-positive HL [3] . However, the significance of EBV-DNA monitoring is debated.…”

mentioning

confidence: 99%

Can We Use EBV-DNA Monitoring to Predict Disease Relapse in EBV-Positive Hodgkin Lymphoma Patients?

Špaček¹,

Hubáček

Marková³

et al. 2010

Acta Haematol

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“…Patients with untreated EBV(+) lymphomas or EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) consistently have EBV DNA detected in plasma, often at high copy number (Martelius et al 2010;Lei et al 2001Lei et al , 2002Kanakry et al 2013;Musacchio et al 2006;Donati et al 2006;Gallagher et al 1999;Elazary et al 2007;Teramura et al 2002;Morishima et al 2014;Suwiwat et al 2007;Beutel et al 2009). Across EBV(+) lymphomas of B-, T-, and NK-cell lineage, EBV DNA has been demonstrated to be detectable in the plasma prior to therapy in the majority of patients and to be markedly elevated in many (Machado et al 2010;Au et al 2004;Kanakry et al 2013).…”

Section: Ebv(+) Lymphomas and Lymphoproliferative Disordersmentioning

confidence: 99%

The Biology and Clinical Utility of EBV Monitoring in Blood

Kanakry

Ambinder

2015

Epstein Barr Virus Volume 2

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Epstein-Barr virus (EBV) DNA in blood can be quantified in peripheral blood mononuclear cells, in circulating cell-free (CCF) DNA specimens, or in whole blood. CCF viral DNA may be actively released or extruded from viable cells, packaged in virions or passively shed from cells during apoptosis or necrosis. In infectious mononucleosis, viral DNA is detected in each of these kinds of specimens, although it is only transiently detected in CCF specimens. In nasopharyngeal carcinoma, CCF EBV DNA is an established tumor marker. In EBV-associated Hodgkin lymphoma and in EBV-associated extranodal NK-/T-cell lymphoma, there is growing evidence for the utility of CCF DNA as a tumor marker.

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Detection of free circulating Epstein-Barr virus DNA in plasma of patients with Hodgkin’s disease

Abstract: EBV DNA was present in 91% of patients with EBV-associated Hodgkins disease, and in all patients with HIV-associated Hodgkins disease. EBV DNA prevalence was higher in patients with advanced disease, irrespective of HIV status.

Cited by 21 publications

References 15 publications

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

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

Can We Use EBV-DNA Monitoring to Predict Disease Relapse in EBV-Positive Hodgkin Lymphoma Patients?

The Biology and Clinical Utility of EBV Monitoring in Blood

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