Disparity analysis and prognostic value of pretreatment whole blood <scp>Epstein‐Barr</scp> virus <scp>DNA</scp> load and Epstein‐Barr encoding region status in lymphomas: A retrospective multicenter study in Huaihai Lymphoma Working Group

Shen, Ziyuan; Hu, Lingling; Yao, Mingkang; He, Chenlu; Liu, Qinhua; Wang, Fei; Gu, Weiying; Wang, Ying; Dong, Maxia; Zhu, Taigang; Yin, Ting; Li, Fēi; Jin, Yingliang; Huang, Shuiping; Zhang, Hao; Sang, Wei

doi:10.1002/ijc.33802

Cited by 16 publications

(19 citation statements)

References 29 publications

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“…2C). Our results tie well with previous studies wherein the PEDL in different EBER groups [17]. Our data is similar to studies from Shen et al [17], nevertheless, the median pretreatment PEDL is much lower than that of them.…”

Section: Discussionsupporting

confidence: 93%

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High plasma EBV-DNA load and positive EBER status associated with viral recurrence and persistent infection in early treatment of lymphoma

et al. 2022

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The relationship between plasma EBV-DNA load (PEDL) and Epstein-Barr virus (EBV)-encoded small RNA (EBER) during early treatment of lymphoma remains unclear. We explored discrepancies in PEDL and variables associated with EBER, and evaluated the consistency between EBER and qualitative analysis of PEDL (qPEDL). Serial measurements of PEDL were performed to determine the dynamic changes of PEDL in early treatment of lymphoma. As a result, the median PEDL of NHL-NKT was higher than that of NHL-B, the median PEDL of ENKTCL was higher than that of DLBCL, and the median PEDL of EBER positive was higher than that of EBER negative. Age, Ki-67 ≧ 80%, Bcl-2 ≧ 80%, p53 and qPEDL were related to EBER. The PEDL could distinguish NHL-B, DLBCL, NHL-NKT and ENKTCL from other lymphoma subtypes. EBER-positive patients spent more time with viral "turn negative (TN)" and "continuous positive (CP)", and less time with viral "continuous negative (CN)". The median PEDL of CP was higher than that of TN. In conclusion, although EBER affects the levels of PEDL in general, it has poor concordance with qPEDL. Our results show, for the rst time, that high PEDL and positive EBER present a strong association with viral recurrence and persistent infection in the early treatment of lymphoma.

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Section: Discussionsupporting

confidence: 93%

“…Our results tie well with previous studies wherein the PEDL in different EBER groups [17]. Our data is similar to studies from Shen et al [17], nevertheless, the median pretreatment PEDL is much lower than that of them. It is worth noting that they have used whole blood samples including circulating tumor cells and other EBV-infected cells.…”

Section: Discussionsupporting

confidence: 93%

High plasma EBV-DNA load and positive EBER status associated with viral recurrence and persistent infection in early treatment of lymphoma

et al. 2022

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“…The prevalence of EBV is higher in developing countries, but our study embraces only a small number of studies in Africa and South America. In addition, although some studies have shown that EBV-DNA can be used as a prognostic marker for EBV-associated HL, the choice of compartments of peripheral blood and cut-off copies of EBV-DNA is different in various studies ( 37 , 51 , 77 , 78 ). Given the different criteria in the related original studies, we did not include the studies of using PCR method to detect EBV infection.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of Epstein−Barr virus infection in Hodgkin lymphoma: A systematic review and meta-analysis

Zhang

Tao

et al. 2022

Front. Oncol.

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IntroductionEpstein−Barr virus (EBV) contributes significantly to the development and occurrence of B-cell lymphomas. However, the association between EBV infection status and clinical outcomes in Hodgkin lymphoma (HL) patients has long been controversial. Therefore, we aimed to estimate the prognostic significance of EBV infection in HL survival.MethodsWe searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant cohort studies from the date of their inception to February 20, 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS), Failure-free survival (FFS), Progression-free survival (PFS), Event-free survival (EFS) and disease-specific survival (DSS) were extracted from the studies or calculated. Subgroup analyses were conducted independently on the five survival outcomes to investigate the source of heterogeneity.ResultsA total of 42 qualified studies involving 9570 patients were identified in our meta-analysis. There was an association between EBV positivity and significantly poorer OS (HR=1.443, 95% CI: 1.250-1.666) and DSS (HR=2.312, 95% CI: 1.799-2.972). However, the presence of EBV in HL showed no effect on FFS, PFS or EFS. In subgroup analyses of OS, DSS and FFS stratified by age groups, EBV positivity was associated with poorer prognosis in elderly patients. Meanwhile, in children and adolescents with EBV-positive HL, we also observed a trend toward a better prognosis, though the results were not statistically significant.ConclusionsEBV-positive status is associated with poor OS and DSS in HL patients. EBV infection should therefore be considered a valuable prognostic marker and risk-stratifying factor in HL, especially in older patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022328708.

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“…EBV infection is closely associated with BL, which leads to the di culties in treating refractory/relapsed BL patients. In addition, high EBV DNA load is associate with poor prognosis in many EBV positive lymphoma subtypes [1,4,5]. However, current treatment options ignored the EBV-positive status of BL due to di culty in eliminating the latent EBV [28].…”

Section: Discussionmentioning

confidence: 99%

“…Despite multi-drugs intensive chemotherapy has improved the prognosis of patients with BL to some extent, patients with refractory/relapsed BL still have poor prognosis, with long-term survival rate of only 10%-20% [2,3]. Moreover, lymphoma patients with high EBV DNA load were shown to have poor prognosis [4][5]. Unfortunately, the current chemotherapy regimens could not eliminate EBV.…”

Section: Introductionmentioning

confidence: 99%

Chidamide induces EBV lytic infection and synergistically with tenofovir eliminate EBV-positive Burkitt lymphoma and inhibit EBV DNA replication

Xu¹,

Zhang²,

Tu³

et al. 2022

Preprint

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Purpose The prognosis of patients with EBV- associated refractory/ relapsed Burkitt lymphoma (BL) is poor and there is no effective way to completely eliminate latent EBV infection. EBV was shown to transform from latency to lytic phase by histone deacetylase (HDAC) inhibitors, and EBV lytic activation could be inhibited by tenofovir, a potent inhibitor of EBV lytic DNA replication. Herein, we explored the anti-tumor effect and EBV clearance ability of novel HDAC inhibitor chidamide combined with tenofovir in EBV positive BL. Methods Raji, Namalwa and CA46 cells were used to evaluate the effects of chidamide combined with tenofovir on their cell viability, cell cycle and apoptosis induction. The EBV DNA copies and mRNA level of EBV related genes were detected by qPCR.Western blotting was performed to detect the cell cycle and apoptosis related pathways in BL cells. BL cell tumor-bearing NSG mice model was used to detect the anti-tumor effects of chidamide combined with tenofovir in vivo. Results In the study, chidamide exhibited HDAC inhibitory activity and downregulated the mRNA levels of HDAC1, 2, 3. Further, chidamide inhibited BL cell proliferation, arrested cell cycle progression, and induced BL cell apoptosis mainly through regulating MAPK pathway. Additionally, chidamide upregulated EBV DNA load and promoted the transcription of lytic genes including BZLF1, BMRF1, BMRF2 and BMLF1. Compared with chidamide alone, the addition of tenofovir further induced growth arrest and apoptosis, inhibited EBV lytic genes transcription and lytic DNA replication induced by chidamide in EBV positive BL cells. Furthermore, our in vivo data showed enhancive tumor-suppression effects of chidamide combined with tenofovir in BL cell tumor-bearing mice model. Conclusions The above data confirmed a synergistic effect of chidamide combined with tenofovir in inducing growth inhibition and apoptosis in EBV-positive BL cells.

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Disparity analysis and prognostic value of pretreatment whole blood Epstein‐Barr virus DNA load and Epstein‐Barr encoding region status in lymphomas: A retrospective multicenter study in Huaihai Lymphoma Working Group

Cited by 16 publications

References 29 publications

High plasma EBV-DNA load and positive EBER status associated with viral recurrence and persistent infection in early treatment of lymphoma

High plasma EBV-DNA load and positive EBER status associated with viral recurrence and persistent infection in early treatment of lymphoma

The prognostic value of Epstein−Barr virus infection in Hodgkin lymphoma: A systematic review and meta-analysis

Chidamide induces EBV lytic infection and synergistically with tenofovir eliminate EBV-positive Burkitt lymphoma and inhibit EBV DNA replication

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