The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases

Kanakry, Jennifer A.; Hegde, Aparna; Durand, Christine M.; Massie, Allan B.; Greer, Amy; Ambinder, Richard F.; Valsamakis, Alexandra

doi:10.1182/blood-2015-09-672030

Cited by 169 publications

(146 citation statements)

References 40 publications

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“…by guest www.bloodjournal.org From prognosis. [15][16][17][18] Strong PDL1 expression correlated with excellent responses. 13 The low-dose pembrolizumab regimen (2 mg/kg) 7 was not associated with significant adverse events, even after allo-HSCT, consistent with safety of immune-checkpoint blockade after allo-HSCT.…”

Section: Pembrolizumab In Refractory Nk/t-cell Lymphomas 2441mentioning

confidence: 99%

PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase

Kwong

Chan

Tan

et al. 2017

Blood

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Section: Pembrolizumab In Refractory Nk/t-cell Lymphomas 2441mentioning

confidence: 99%

PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase

Kwong

Chan

Tan

et al. 2017

Blood

411

331

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“…Latent Epstein–Barr virus (EBV) can induce malignancies such as lymphoma and nasopharyngeal carcinoma . Lo et al .…”

Section: Can Ctdna Be Used In Cancer Screening Programmes In Definedmentioning

confidence: 99%

Cell‐free tumour DNA testing for early detection of cancer – a potential future tool

et al. 2019

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In recent years, detection of cell‐free tumour DNA (ctDNA) or liquid biopsy has emerged as an attractive noninvasive methodology to detect cancer‐specific genetic aberrations in plasma, and numerous studies have reported on the feasibility of ctDNA in advanced cancer. In particular, ctDNA assays can capture a more ‘global’ portrait of tumour heterogeneity, monitor therapy response, and lead to early detection of resistance mutations. More recently, ctDNA analysis has also been proposed as a promising future tool for detection of early cancer and/or cancer screening. As the average proportion of mutated DNA in plasma is very low (0.4% even in advanced cancer), exceedingly sensitive techniques need to be developed. In addition, as tumours are genetically heterogeneous, any screening test needs to assay multiple genetic targets in order to increase the chances of detection. Further research on the genetic progression from normal to cancer cells and their release of ctDNA is imperative in order to avoid overtreating benign/indolent lesions, causing more harm than good by early diagnosis. More knowledge on the sources and elimination of cell‐free DNA will enable better interpretation in older individuals and those with comorbidities. In addition, as white blood cells are the major source of cell‐free DNA in plasma, it is important to distinguish acquired mutations in leukocytes (benign clonal haematopoiesis) from an upcoming haematological malignancy or other cancer. In conclusion, although many studies report encouraging results, further technical development and larger studies are warranted before applying ctDNA analysis for early cancer detection in the clinic.

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“…With the rapid development of real-time quantitative PCR, the measurement of EBV DNA load (EDL) during these EBV-associated diseases has been largely implemented in clinical practice (3)(4)(5). The monitoring of EDL in blood is required for transplant recipients at risk of posttransplantation lymphoproliferative disorders (PTLDs) and could also be a surrogate marker for the adjustment of the immunosuppressive regimen in these patients (6,7).…”

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confidence: 99%

Multicenter Evaluation of Whole-Blood Epstein-Barr Viral Load Standardization Using the WHO International Standard

et al. 2016

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The first WHO international standard for Epstein-Barr virus (EBV) (WHO EBV standard) for nucleic acid amplification technology (NAT)-based assays was commercialized in January 2012 by the National Institute for Biological Standards and Control. In the study reported here, we compared whole-blood EBV DNA load (EDL) results from 12 French laboratories for seven samples (Quality Controls for Molecular Diagnostics 2013 proficiency panel) in order to determine whether expression in international units reduces interlaboratory variability in whole-blood EDLs. Each testing laboratory used a conversion factor to convert EDL results from copies per milliliter to international units per milliliter. This conversion factor was calculated from the WHO EBV standard according to the protocol described in this study (nine laboratories) or the recommendations of the PCR kit suppliers (three laboratories). The interlaboratory variability in whole-blood EDL results was reduced after standardization of the results using the WHO EBV standard. For the seven samples tested, standard deviations (SD) ranged from 0.41 to 0.55 when the results were expressed in log copies per milliliter, whereas the SD ranged from 0.17 to 0.32 when results were given in log international units per milliliter. Comparing the variance data (F test), we showed that the dispersion of whole-blood EDL results was significantly lower when they were expressed in log international units per milliliter (P < 0.001 for six of seven samples and P < 0.05 for one sample with a low mean EDL of 2.62 log IU/ml). This study showed that the use of the WHO EBV standard could improve the homogeneity of whole-blood EDL results between laboratories as well as the monitoring of patients at high risk of posttransplant lymphoproliferative disorders or other EBV-associated diseases. Primary Epstein-Barr virus (EBV) infection is the cause of the vast majority of cases of infectious mononucleosis and the subsequent lifelong persistence of EBV in the host, which, although mostly asymptomatic, can lead to the development of several lymphoid and epithelial cancers in immunosuppressed and immunocompetent individuals (1, 2).With the rapid development of real-time quantitative PCR, the measurement of EBV DNA load (EDL) during these EBV-associated diseases has been largely implemented in clinical practice (3-5). The monitoring of EDL in blood is required for transplant recipients at risk of posttransplantation lymphoproliferative disorders (PTLDs) and could also be a surrogate marker for the adjustment of the immunosuppressive regimen in these patients (6, 7). EDL measurement in plasma also appears to be a useful biomarker for the management of EBV-associated undifferentiated nasopharyngeal carcinoma (8). Although less clearly demonstrated, EDL measurements could also be helpful in other clinical situations such as severe or atypical infectious mononucleosis and other EBV-associated malignancies in immunosuppressed or immunocompetent patients (3, 9).Besides the debates on the clinical utility ...

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The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases

Abstract: • Cell-free (plasma) EBV DNA performs better than cellular EBV DNA as a marker of a broad range of EBV 1 diseases.• Within a largely immunocompromised and hospitalized cohort, detection of EBV DNA in plasma is uncommon in the absence of EBV 1 disease.

Cited by 169 publications

References 40 publications

PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase

PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase

Cell‐free tumour DNA testing for early detection of cancer – a potential future tool

Multicenter Evaluation of Whole-Blood Epstein-Barr Viral Load Standardization Using the WHO International Standard

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