Clinical Significance of Plasma Epstein-Barr Virus DNA in Peripheral T-Cell Lymphomas

2021 ◽  
pp. 1-12
Author(s):  
Danqing Zhao ◽  
Shaoxuan Hu ◽  
Daobin Zhou ◽  
Yan Zhang ◽  
Wei Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Prognostic Factor ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
Disease Relapse ◽  
First Line ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Pre Treatment

<b><i>Introduction:</i></b> The clinical implications of plasma Epstein-Barr virus (EBV) DNA in patients with peripheral T-cell lymphoma (PTCL) remain unclear. <b><i>Objective:</i></b> This study aimed to explore the clinical correlations of pre- and post-treatment plasma EBV-DNA concentrations with treatment outcomes and prognosis in patients with PTCL. <b><i>Methods:</i></b> We retrospectively reviewed 128 patients diagnosed with PTCL with available data on pre-treatment plasma EBV-DNA, including 63 patients for whom post-treatment plasma EBV-DNA data were also available. Patients with extra-nodal NK/T-<X00_Del_TrennDivis></X00_Del_TrennDivis>cell lymphoma were excluded from this study. <b><i>Results:</i></b> Pre-treatment plasma EBV-DNA was elevated (e.g., ≥500 copies/mL) in 35.2% of PTCL patients, with significant differences in positive rates between different subtypes of PTCL (<i>p</i> &#x3c; 0.001). High pre-treatment EBV-DNA concentrations were associated with advanced age (&#x3e;60 years), elevated lactate dehydrogenase levels, high International Prognostic Index (IPI), and positive EBV-encoded RNAs-ISH in tumor specimens. In multivariate analyses, pre-treatment EBV-DNA ≥500 copies/mL was an independent prognostic factor after adjusting for IPI and pathological subtypes (hazard ratio = 2.14, <i>p</i> = 0.032). For patients with elevated pre-treatment EBV-DNA, normalization of EBV-DNA concentrations after first-line chemotherapy was significantly associated with better overall response rate (81.3% vs. 22.2%, <i>p</i> = 0.014), progression-free survival (12.0 months vs. 3.7 months, <i>p</i> = 0.011), and overall survival (37.9 months vs. 7.8 months, <i>p</i> = 0.012). For patients achieving remission to first-line therapy, rebound of EBV-DNA levels during follow-up was associated with disease relapse or progression. <b><i>Conclusions:</i></b> These results suggest that pre-treatment plasma EBV-DNA concentration is a strong prognostic factor for PTCL. For patients with elevated pre-treatment EBV-DNA, dynamic monitoring of EBV-DNA changes after initiation of therapy is useful for predicting treatment outcome and disease relapse.

scholarly journals Superiority of Epstein-Barr Virus DNA in the Plasma Over Whole Blood for Prognostication of Extranodal NK/T Cell Lymphoma

2020 ◽  
Vol 10 ◽  
Author(s):  
Joo Young Ha ◽  
Hyungwoo Cho ◽  
Heungsup Sung ◽  
Ah Ra Jung ◽  
Yoon Sei Lee ◽  
...  
Keyword(s):  
T Cell ◽  
Whole Blood ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
Treatment Completion ◽  
Survival Outcomes ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Pre Treatment

BackgroundExtranodal natural killer T cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma with invariable infection of lymphoma cells with Epstein-Barr virus (EBV), and the presence of EBV-DNA in the blood is a well-known prognosticator. However, there is no consensus on which blood compartment is more optimal for predicting survival outcomes.MethodsWe analyzed 60 patients who were newly diagnosed with ENKTL from a prospectively collected database. EBV-DNA was measured in the whole-blood (WB) and plasma at the time of diagnosis and after treatment completion.ResultsEBV-DNA was detected in pre-treatment WB and plasma in 37 (61.7%) and 23 (38.3%) patients, respectively. The presence of pre-treatment plasma EBV-DNA was significantly associated with advanced stage while presence of WB EBV-DNA did not. Positivity of pre-treatment plasma-EBV, but not WB EBV-DNA, was independently associated with poor PFS (HR, 4.22;95% CI, 1.79–9.97; P=0.001) and OS (HR, 8.38; 95% CI, 3.03–23.19; P&lt;0.001) in the multivariate analysis. After treatment completion, positivity of plasma-EBV was independently associated with poor PFS (HR, 9.41; 95% CI, 2.27–39.02; P=0.002) and OS (HR, 32.38; 95% CI, 3.25–322.56; P=0.003), whereas no significant association was observed between WB-EBV status and survival outcomes.ConclusionsOur results suggest that EBV-DNA in the plasma has better prognostic values than WB in patients with ENKTL.

scholarly journals Extranodal NK/T-Cell Lymphoma, Nasal Type: Genetic, Biologic, and Clinical Aspects with a Central Focus on Epstein–Barr Virus Relation

2021 ◽  
Vol 9 (7) ◽  
pp. 1381
Author(s):  
Miki Takahara ◽  
Takumi Kumai ◽  
Kan Kishibe ◽  
Toshihiro Nagato ◽  
Yasuaki Harabuchi
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Clinical Aspects ◽  
Lymphoma Cells ◽  
Nasal Type ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Extranodal NK/T-Cell Lymphoma, nasal type (ENKTL-NT) has some salient aspects. The lymphoma is commonly seen in Eastern Asia, has progressive necrotic lesions in the nasal cavity, makes midfacial destructive lesions, and shows poor prognosis. The lymphoma cell is originated from either NK- or γδ T-cells, which express CD56. Since the authors first demonstrated the existence of Epstein–Barr virus (EBV) DNA and EBV oncogenic proteins in lymphoma cells, ENKTL-NT has been recognized as an EBV-associated malignancy. Because the angiocentric and polymorphous lymphoma cells are mixed with inflammatory cells on a necrotic background, the diagnosis of ENKTL-NT requires CD56 immunostaining and EBER in situ hybridization. In addition, serum the EBV DNA level is useful for the diagnosis and monitoring of ENKTL-NT. Although ENKTL-NT is refractory lymphoma, the prognosis is improved by the development of therapies such as concomitant chemoradiotherapy. The basic research reveals that a wide variety of intracellular/cell surface molecules, cytokines, chemokines, and micro RNAs are involved in lymphomagenesis, and some of them are related to EBV. Understanding lymphoma behavior introduces new therapeutic strategies, such as the usage of immune checkpoint inhibitors, peptide vaccines, and molecular targeting therapy. This review addresses recent advances in basic and clinical aspects of ENKTL-NT, especially its relation to EBV features.

scholarly journals The Clinical Utility of Circulating Epstein-Barr Virus DNA Concentrations in NK/T-Cell Lymphoma: A Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Ze-Long Liu ◽  
Xi-Wen Bi ◽  
Pan-Pan Liu ◽  
De-Xin Lei ◽  
Wen-Qi Jiang ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Utility ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
Meta Analysis ◽  
T Cell Lymphoma ◽  
Barr Virus ◽  
Ebv Dna ◽  
Nk T Cell ◽  
Epstein Barr

Background. Circulating Epstein-Barr virus (EBV) DNA concentrations were reported to have prognostic value for NK/T-cell lymphoma patients in limited small-scale studies. In this study, we aimed to evaluate the clinical utility of circulating EBV-DNA concentrations to a large sample of NK/T-cell lymphoma patients. Methods. We conducted this meta-analysis, which included a total of 15 prospective and retrospective comparable studies to assess the association between pretreatment EBV-DNA (pre-DNA), posttreatment EBV-DNA (post-DNA), and clinical outcomes of NK/T-cell lymphoma patients. We chose overall survival (OS) as the primary endpoint and progression-free survival (PFS), complete response (CR), and overall response rate (ORR) as secondary endpoints. Results. High pre-DNA and detectable post-DNA were both significantly correlated with poorer OS in NK/T-cell lymphoma patients (P<0.05), with hazard radios (HRs) equal to 3.45 and 2.30, respectively. High pre-DNA and detectable post-DNA also predicted poorer PFS. Additionally, high pre-DNA was found to be significantly correlated with both worse CR and ORR, which indicated worse treatment response. Conclusion. Circulating EBV-DNA concentrations provides prognostic values of survival and treatment response in NK/T-cell lymphoma patients.

scholarly journals Predictive value of therapeutic monitoring with plasma Epstein-Barr virus DNA in Extranodal NK/T cell lymphoma, nasal type

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5363-5363
Author(s):  
Chengcheng Guo ◽  
He Huang ◽  
Ying Tian ◽  
Xueying Li ◽  
Mengping Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Nasal Type ◽  
Barr Virus ◽  
Ebv Dna ◽  
Nk T Cell ◽  
Epstein Barr

Abstract Predictive value of therapeutic monitoring with plasma Epstein-Barr virus DNA in Extranodal NK/T cell lymphoma, nasal type Background: Predictive tumor markers are essential for extranodal NK/T cell lymphoma, nasal type (ENKTL), which pursues an aggressive clinical course with poorer prognosis. This prospective study was conducted to evaluate the dynamic monitoring value of circulating EBV DNA concentration for the prediction of ENKL during treatment. Method: Patients with untreated, centrally reviewed diagnosis of ENKTL were included in our study. Plasma Epstein-Barr virus (EBV) DNA levels were collected before and/or every 2 cycles of chemotherapies for circulating EBV DNA measurement by a real-time PCR assay. Result: From Jan 2002 to Aug 2012, 113 newly diagnostic ENKTL patients enrolled. The positive rate of circulating EBV DNA is 61.9% (70/113) with a median concentration of 1.21×103copies/ml. Patients who had initial positive circulating EBV-DNA had more lymph nodes invasion, higher IPI and KPI score. The more advance of the stage, the higher rate of the circulating EBV-DNA positive. When divided the positive group as low and high-dose ones by the cut-off value as 2×104copies/ml, the CR rate of the high-dose group is much lower and the 5-year OS is significantly better than the low-dose group and the negative group. After two cycles of chemotherapy, 45 patients were tested circulating EBV-DNA and 53.33% (24/45) patients became negative EBV-DNA candidates. There were 87.5% (21/24) patients obtained complete remission at the end of the treatment, comparing as 42.86% (9/21) in the still positive EBV-DNA groups(P= 0.002). There is a tendency that the patients whose circulating EBV-DNA become negative after two cycles will have better prognosis (5-year OS: 75% vs 46%, P=0.074). The similar situation of CR rate and OS happened in the EBV-DNA detection of completion of total chemotherapy. 7 of 13 relapsed pts of ＞1×103copies/ml EBV-DNA at the time of recurrent, and the survival outcome was dismal for them compared to the other 6 pts of ≤1×103copies/ml（5- year OS: 0% vs 80%, P=0.001） Conclusion: Circulating EBV-DNA level can predict the efficacy of treatment as a dynamic marker of ENKL. Patients with early positive detection of EBV-DNA after 2 cycles of chemotherapy maybe received more aggressive treatments. Disclosures No relevant conflicts of interest to declare.

scholarly journals Circulating cell‐free epstein–barr virus DNA levels and clinical features in Moroccan patients with nasopharyngeal carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Amina Gihbid ◽  
Raja Benzeid ◽  
Abdellah Faouzi ◽  
Jalal Nourlil ◽  
Nezha Tawfiq ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Disease Stage ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Pre Treatment ◽  
Moroccan Patients

Abstract Background The identification of effective prognosis biomarkers for nasopharyngeal carcinoma (NPC) is crucial to improve treatment and patient outcomes. In the present study, we have attempted to evaluate the correlation between pre-treatment plasmatic Epstein-Barr virus (EBV) DNA load and the conventional prognostic factors in Moroccan patients with NPC. Methods The present study was conducted on 121 histologically confirmed NPC patients, recruited from January 2017 to December 2018. Circulating levels of EBV DNA were measured before therapy initiation using real-time quantitative PCR. Results Overall, undifferentiated non-keratinizingcarcinoma type was the most common histological type (90.1 %), and 61.8 % of patients were diagnosed at an advanced disease stage (IV). Results of pre-treatment plasma EBV load showed that 90.9 % of patients had detectable EBV DNA, with a median plasmatic viral load of 7710 IU/ml. The correlation between pre-treatment EBV DNA load and the conventional prognostic factors showed a significant association with patients’ age (p = 0.01), tumor classification (p = 0.01), lymph node status (p = 0.003), metastasis status (p = 0.00) and overall cancer stage (p = 0.01). Unexpectedly, a significant higher level of pre-treatment EBV DNA was also found in plasma of NPC patients with a family history of cancer (p = 0.04). The risk of NPC mortality in patients with high pretreatment EBVDNA levels was significantly higher than that of those with low pre-treatment plasma EBV-DNA levels (p < 0.05). Furthermore, patients with high pre-treatment EBV-DNA levels (≥ 2000, ≥ 4000) had a significant low overall survival (OS) rates (p < 0.05). Interestingly, lymph node involvement, metastasis status and OS were found to be the most important factors influencing the EBV DNA load in NPC patients. Conclusions The results of the present study clearly showed a high association between pre-treatment EBV DNA load, the crucial classical prognostic factors (T, N, M and disease stage) of NPC and OS, suggesting that pre-treatment EBV DNA can be a useful prognostic biomarker in clinical decision-making and improving NPC treatment in Morocco.

Peripheral T-cell Lymphoma, NOS With Epstein-Barr Virus Positivity in an Elderly Patient With Myelodysplastic Syndrome: An Autopsy Case Report

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S81-S81
Author(s):  
J Lanceta ◽  
W Xue ◽  
M Hurford ◽  
H Wu
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Barr Virus ◽  
Epstein Barr

Abstract Casestudy Epstein-Barr virus (EBV)-associated peripheral T-cell lymphomas are a group of aggressive neoplasms with a geographic predilection for South America and Asia, but are very rare in Western populations. Results We report a case of a 74-year-old Caucasian female who presented with pancytopenia and B symptoms with EBV-IgG detected on admission. Past medical history included: ITP, chronic urticaria, and recently diagnosed myelodysplastic syndrome (MDS) on bone marrow biopsy one month prior to admission. Excisional biopsies of an enlarged right neck lymph node (repeated within 6 months) and right axillary lymph node five years ago were negative for a lymphoproliferative disorder at the time. Repeated bone marrow biopsy, performed during the current admission, confirmed the diagnosis of MDS, with scattered T-cells without aberrant immunophenotype. Despite aggressive treatment from multiple specialties, the patient deteriorated and expired four weeks later from complications of MDS. At autopsy, there was diffuse lymphadenopathy involving the mediastinum, axilla, pelvis and peripancreatic fat. Lymph node sections demonstrated nodal architecture effacement by diffuse, vaguely nodular lymphoid infiltrates. Histologically, the infiltrates were composed of medium to large lymphocytes with round to slight irregular nuclei, rare Reed-Sternberg-like multinucleated cells, clumped chromatin, and indistinct nucleoli. Individual cell necrosis was abundant with mitotic figures readily identifiable. Immunohistochemistry revealed CD2+ CD3+ neoplastic T-cells that co-express MUM1 and a subset of CD30, while negative for CD4, CD5, CD8, CD56, ALK1, and TDT. EBV-encoded RNA in-situ hybridization was focally positive. The final postmortem diagnosis was peripheral T-cell lymphoma, not otherwise specified (NOS), with focal EBV positivity. Conclusion Co-existence of a de-novo MDS and non-Hodgkin lymphoma without any prior chemotherapeutic exposure is a highly unusual finding, although MDS-like presentations can occur with EBV-associated lymphomas. Peripheral T-cell lymphoma, NOS is an aggressive lymphoma and EBV positivity has been found correlated with a poor prognosis. This case demonstrates how postmortem examination remains an important tool in clinical- pathological correlation and highlights the potential pathogenetic role EBV plays in MDS and T-cell lymphoma.

Unusual presentation of an Epstein barr virus-negative extranodal natural killer/T cell lymphoma: A diagnostic dilemma

2021 ◽  
Vol 0 ◽  
pp. 1-4
Author(s):  
Sindhu Kilaru ◽  
Soumya Surath Panda ◽  
Sourav Mishra ◽  
Debahuti Mohapatra ◽  
Spoorthy Kolluri ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Natural Killer T Cell ◽  
Barr Virus ◽  
Epstein Barr ◽  
Killer T Cell ◽  
Natural Killer T

Extra-nodal Natural killer/T cell lymphoma (ENKTL) is a well-defined and highly aggressive form of NonHodgkin’s lymphoma with a scarcity of cases reported in literature. The most common primary site of involvement is the nasal cavity followed by skin and the gastrointestinal tract (GIT). Cutaneous involvement is a rarity. More than 95% of cases are usually in association with Epstein Barr Virus (EBV) infection. EBV negative ENKTL can be similar in clinical, pathological, and prognostic characteristics with EBV positive ENKTL. This malignancy is usually characterized by its poor prognosis irrespective of clinical stage and therapy. We describe here, a 58-year-old man presenting with multiple nodular lesions over legs and trunk, had an ileal perforation later, and was diagnosed as ENKTL on the ileal biopsy specimen. This case is being reported in view of the fulminant clinical course of the disease, simultaneous involvement of the GIT and skin without nasal or midline involvement, the usefulness of immunohistochemistry in arriving at a diagnosis, and EBV negativity which is quite rare in the Asian population.

scholarly journals A Case of Cutaneous Epstein-Barr Virus-Associated Diffuse Large B-Cell Lymphoma in an Angioimmunoblastic T-Cell Lymphoma

2016 ◽  
Vol 28 (6) ◽  
pp. 789 ◽  
Author(s):  
Mi-Hye Lee ◽  
Ik-Jun Moon ◽  
Woo-Jin Lee ◽  
Chong-Hyun Won ◽  
Sung-Eun Chang ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Angioimmunoblastic T Cell Lymphoma ◽  
Barr Virus ◽  
Large B Cell Lymphoma ◽  
Epstein Barr ◽  
Large B Cell
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