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
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DOI：
10.1182/blood-2012-09-454694
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发表时间：
2013-05-02
期刊：
影响因子：
20.3
通讯作者：
Ambinder, Richard F.
中科院分区：
文献类型：
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作者：
Kanakry, Jennifer A.;Li, Hailun;Ambinder, Richard F.
EB病毒（Epstein-Barr virus，EBV）与霍奇金淋巴瘤（Hodgkin lymphoma，HL）相关，可通过病毒核酸原位杂交（in-situ hybridization，ISH）在肿瘤细胞中检测到。我们试图确定血浆EBV-DNA是否可以作为EBER-ISH的替代物，并探讨其在HL中的预后效用。来自癌症协作组间试验E2496的样本用于比较治疗前血浆EBV-DNA定量与EBER-ISH的EBV肿瘤状态。以>60个病毒拷贝/100 μ L血浆为临界值，与EBER-ISH的一致性为96%。治疗前和第6个月的血浆标本按此临界值指定为EBV（-）或EBV（1）。与治疗前EBV（-）血浆患者（n = 274）相比，治疗前EBV（1）血浆患者（n = 54）的无失败生存期（FFS）较差，对数秩P = 0.009。相比之下，当患者按EBER-ISH分层时，FFS没有观察到差异。多因素分析显示，治疗前血浆EBV阳性是治疗失败的独立预测因子。第6个月时，血浆EBV（1）患者（n = 7）的FFS低于血浆EBV（-）患者（n = 125），对数秩P = 0.007。这些结果证实了血浆EBV-DNA与HL中的EBER-ISH高度一致，并表明其在基线和治疗后均具有预后效用。该试验在www.clinicaltrials.gov上注册为#NCT00003389。
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 mu L 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 = 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(1) 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.