Prospective Measurement of EBV-DNA in Plasma and Peripheral Blood Mononuclear Cells of Extranodal NK/T-Cell Lymphoma, Nasal Type.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 135-135
Author(s):  
Ritsuro Suzuki ◽  
Motoko Yamaguchi ◽  
Koji Izutsu ◽  
Go Yamamoto ◽  
Kenzo Takada ◽  
...  
Keyword(s):  
Overall Survival ◽  
Peripheral Blood ◽  
Copy Number ◽  
Mononuclear Cells ◽  
Clinical Stage ◽  
Performance Status ◽  
First Line ◽  
Dna Copy Number ◽  
Nasal Type ◽  
Ebv Dna

Abstract Abstract 135 Background: Peripheral blood of patients with extranodal NK/T-cell lymphoma, nasal type (ENKL) contains fragmented Epstein-Barr virus (EBV) DNA. Measurement of the circulating viral DNA load has been reported to be useful for the diagnosis, monitoring and prognostication of the disease. However, there are two different subjects for analysis, plasma/serum component and mononuclear cells (MNC). Most reports do not compare both samples from the same patients, and are biased by a retrospective manner of accrual. Therefore, it remains unclear which samples are more useful subjects. Materials and Methods: To evaluate clinical significance of peripheral blood EBV-DNA copy number for ENKL, we conducted a prospective study to analyze EBV-DNA with quantitative polymerase chain reaction. Inclusion criteria are as follows: (1) Diagnosis of ENKL or aggressive NK-cell leukemia by biopsy or cytology. (2) Patients without other serious complications and those tolerable for chemotherapy and/or radiotherapy. (3) No prior history of chemotherapy or radiotherapy. (4) Patients with written informed consent. Primary endpoint was a prognostic value of EBV-DNA copy number to predict 2-year overall survival. Secondary endpoints were comparison of EBV-DNA copy number and pretreatment characteristics and prognostic capability of EBV-DNA during/after treatments. Three times of analysis, pre-treatment, mid-treatment, post-treatment, at central laboratory was to be performed for each patient. Results: A total of 33 patients were registered from June 2004 to March 2007. All patients were diagnosed with ENKL and male/female ratio was 21/12. The median age was 56 years old, ranging from 18 to 81. 19 patients were in stage IE, 3 in stage IIE, and 11 in stage IV. 13 patients had B-symptom and 14 had elevated serum LDH level. ECOG performance status was low (0–2) in 29 patients, but was 3 in 2 patients. IPI was high-intermediate/high in 11. First line treatment included concurrent chemoradiotherapy in 16, radiotherapy followed by chemotherapy in 8, and chemotherapy alone in 6. Pretreatment MNC and plasma EBV-DNA were detectable in 6 and 14 patients, respectively. The maximum copy numbers were 780 copies/microgram DNA for MNC and 71000 copies/mL for plasma. Significant correlation was observed between mononuclear and plasma EBV-DNA copies (r = 0.8741, P < 0.0001). Plasma EBV-DNA well correlated with pretreatment clinical stage (P = 0.02), presence of B-symptom (P = 0.02), ECOG PS (P = 0.02), serum LDH level (P = 0.05), and soluble IL-2 receptor (P < 0.0001), but not with regional node involvement (P = 0.17), nasal vs. nasal-type (P = 0.16), and serum C-reactive protein (P = 0.29). Among 28 patients evaluable for response, 21 patients responded (CR/PR) to the first line treatment. Mean plasma EBV-DNA copy number before treatment was significantly higher in non-responders compared to responders (16472 copies/mL vs 2645 copies/mL, P = 0.02). 2-year overall survival was 69.7%. The median follow-up of patients was 2.9 years. Clinical stage, performance status, pretreatment plasma EBV-DNA and pretreatment mononuclear cell EBV-DNA were significant prognostic factors for overall survival by univariate analysis. Multivariate analysis showed clinical stage (hazard ratio = 9.0, 95% confidence interval: 1.8–45.0) and pretreatment plasma EBV-DNA (hazard ratio = 10.6, 95% confidence interval: 1.3–87.0) were significant prognostic factors. 2-year overall survival of plasma EBV-DNA positive and negative patients was 42.9% and 94.4%, respectively (Figure, P = 0.0009). Conclusions: Our study shows pretreatment plasma EBV-DNA copy number is a good indicator for both response to treatment and overall survival. Measurement of the plasma EBV-DNA is useful for prospective clinical trials and general practice. Disclosures: Oshimi: Eisai Pharmaceutical Company: Employment.

scholarly journals EBV- DNA Viral Load in Peripheral Blood Mononuclear Cells of Patients with Chronic Lymphocytic Leukemia Is Associated with Unfavorable Prognosis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1965-1965
Author(s):  
Jacek Rolinski ◽  
Ewelina Grywalska ◽  
Marcin Pasiarski ◽  
Agnieszka Stelmach-Goldys ◽  
Agata Surdacka ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Lymphocyte Count ◽  
Copy Number ◽  
Mononuclear Cells ◽  
Clinical Course ◽  
Dna Copy Number ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Ebv Dna

Abstract Background: Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus that infects more than 90% of the world population. Following primary infection in the oropharynx, EBV remains latently present in B cells. Asymptomatic EBV reactivations periodically occur in oral mucosa-associated lymphoid tissues in healthy carriers. B cells infected by EBV are suspected to be involved in the etiology of various human lymphoma. Previously, EBV reactivation has been diagnosed by serologic IgG, IgM, IgA profiles that suggested virus replication. However, serologic responses, in immunocompromised subjects, like patients with chronic lymphocytic leukemia (CLL), do not necessarily indicate ongoing replicative activity. CLL is the most frequent form of leukemia in adults in western countries. Despite by definition chronic character, CLL is characterized by marked heterogeneity. Potential involvement of EBV in the pathogenesis of CLL is still to be explain. Latent EBV infection in healthy carriers is controlled by a cell-mediated immune response that is impaired in CLL patients and might result in poor control of EBV infection. Since EBV may activate B cells, stimulate their proliferation and inhibit their apoptosis, we hypothesize that it could contribute to unfavorable clinical course of CLL and may be one of reason of its heterogeneity. Objective: The aim of this study was to determine whether EBV-DNA load in the peripheral blood mononuclear cells (PBMCs) of CLL patients may influence heterogeneity in clinical course of the disease. We analyzed the association between EBV-DNA load in PBMC and stage of the disease, adverse prognostic factors (including CD38 and ZAP-70 expression and cytogenetic abnormalities) and clinical outcome. Material and methods: Peripheral blood samples were obtained from 115 untreated CLL patients and 20 healthy individuals. Real-time PCR was used to quantitate EBV-DNA copy number in PBMCs (viral load). As the sensitivity of the system amounts to 10 copies per µl, all the samples with the EBV-DNA copy number below this detection threshold were considered EBV-negative. The immunophenotype of peripheral blood lymphocytes was analyzed by flow cytometer. Results: Detectable EBV-DNA load in PBMCs was found in 62 out of 115 CLL patients (53.91%). The median EBV-DNA copy number in these group was 184 per 1 µg DNA (range: 12.79-8957.69). The EBV-DNA copy number per 1 µg DNA was significantly higher in patients who required the treatment (p<0.0001) than in untreated ones, in patients with lymphocyte count doubling time <12 months than in than patients with lymphocyte count doubling time >12 months (p<0.0001), in patients with hepatomegaly (p=0.023) and, splenomegaly (p=0.005) than in patients without organomegaly. It was also significantly higher in patients with CD38 (p<0.0001) and ZAP-70 expression (p=0.008) comparing to the patients CD38- and ZAP-70-, respectively, as well as in the patients with del (11q22.3) as comparing to the patients without this cytogenetic abnormality. Furthermore, the EBV-DNA copy number per 1 µg DNA showed significant positive correlation with the concentrations of LDH (r=0.531, p=0.00001) and beta-2-microglobulin (r=0.425, p=0.00057). The presence of more than 12.79 copies of EBV DNA in 1 µg DNA isolated from PBMCs was associated with reduced time to first treatment (p=0.00001), and lymphocyte count doubling-free survival (p<0.000001). Conclusions: We proved for the first time, that higher of EBV-DNA copy number in PBMCs of patients with CLL is associated with adverse prognostic factors as well as more progressive clinical course of the disease expressed by reduced time to first treatment. These results suggest that higher of EBV-DNA copy number in peripheral blood mononuclear cells blood predicts poor clinical outcome of CLL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Cell-free EBV DNA in Hodgkin lymphoma.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 7-7
Author(s):  
Jennifer Ann Kanakry ◽  
Lan L. Gellert ◽  
Yvette L. Kasamon ◽  
M. Victor Lemas ◽  
Marie Valerie Toure ◽  
...  
Keyword(s):  
Tumor Marker ◽  
Hodgkin Lymphoma ◽  
Copy Number ◽  
Mononuclear Cells ◽  
Prospective Trial ◽  
Prognostic Significance ◽  
Dna Copy Number ◽  
Paired Samples ◽  
Ebv Dna ◽  
Pre Treatment

7 Background: EBV is associated with a subset of Hodgkin lymphoma (HL), identified by tissue-based techniques such as EBER in situ hybridization of tumor specimens. Recent evidence suggests that cell-free EBV DNA may be a surrogate for EBER and serve as a tumor marker in HL. Methods: EBV DNA copy number was quantitated by RT-PCR of plasma, serum, and peripheral blood mononuclear cells (PBMCs) from HL patients and compared using Pearson’s correlation. Receiver operator characteristic (ROC) curves determined thresholds for EBV DNA copy number to discriminate EBER status. Kaplan-Meier curves and Cox proportional hazards models were constructed to analyze failure-free survival (FFS). Results: Plasma and serum EBV DNA (n=30 paired samples) were correlated (r=0.96, p<0.0001), while plasma and PBMC EBV DNA were not correlated (n= 25 paired samples, r=0.35, p=N.S.). Detectable plasma EBV DNA was 85% concordant with EBER status (n=34 paired samples) while detectable PBMC EBV DNA had a low concordance of 50% with EBER (n=78 paired samples). In a prospective clinical trial of HL patients treated with rituximab-ABVD, we confirmed the association between pre-treatment plasma EBV DNA and EBER (n=33 paired samples) and found a cut-off of > 60 viral copies/100 µL plasma to have optimal test characteristics with 100% sensitivity, 93% specificity, and 94% concordance with EBER. We observed that EBV DNA was cleared from the plasma of patients with EBER(+) HL within one month of treatment, corresponding to a durable remission in each instance. In a larger prospective trial of HL (E2496), pre-treatment plasma EBV DNA was 95% concordant with EBER (n=121 paired samples), with a sensitivity of 92% and specificity of 96% at the same cut-off of 60 viral copies/100 µL plasma. Pre-treatment plasma EBV DNA positivity was found to be an independent predictor of inferior FFS with a hazard ratio of 2.0 (95% CI 1.2 – 3.5), as presented at ASCO 2012 (abstract #8003). Failure to clear the plasma of EBV with treatment corresponded to inferior 3-year FFS (44% vs 69%, log-rank p=0.03). Conclusions: These findings suggest that cell-free EBV DNA may be a useful tumor marker in HL, demonstrating concordance with EBER, prognostic significance prior to therapy, and utility as a marker of treatment response during therapy.

scholarly journals Prospective measurement of Epstein-Barr virus–DNA in plasma and peripheral blood mononuclear cells of extranodal NK/T-cell lymphoma, nasal type

Blood ◽  
2011 ◽  
Vol 118 (23) ◽  
pp. 6018-6022 ◽  
Author(s):  
Ritsuro Suzuki ◽  
Motoko Yamaguchi ◽  
Koji Izutsu ◽  
Go Yamamoto ◽  
Kenzo Takada ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
Cell Lymphoma ◽  
Clinical Stage ◽  
T Cell Lymphoma ◽  
Nasal Type ◽  
Barr Virus ◽  
Ebv Dna ◽  
Nk T Cell ◽  
Epstein Barr

Abstract Epstein-Barr virus (EBV)–DNA was prospectively analyzed in plasma and mononuclear cells (MNCs) from peripheral blood in patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type, to evaluate the clinical significance for diagnosis, monitoring the tumor burden, and prognostication. Thirty-three patients were enrolled, and 32 were evaluable. Pretreatment plasma and MNC EBV-DNA was detectable in 14 (range, 50-71 000 copies/mL) and 6 patients (range, 20-780 copies/μg DNA), respectively, and both were well correlated (r = 0.8741, P < .0001). Detectable plasma EBV-DNA was associated with higher clinical stage (P = .02), presence of B symptoms (P = .02), worse performance status (P = .02), and higher serum soluble IL-2 receptor level (P < .0001). Twenty-two patients attained complete response. Plasma EBV-DNA level was significantly higher in nonresponders than in responders (mean, 16 472 vs 2 645 copies/mL; P = .02). Multivariate analysis showed clinical stage (hazard ratio, 9.0; 95% confidence interval, 1.8%-45.0%) and pretreatment plasma EBV-DNA (hazard ratio, 10.6; 95% confidence interval, 1.3%-87.0%) were significant prognostic factors. Three-year overall survival of plasma EBV-DNA positive and negative patients was 42.9% and 94.4%, respectively (P = .0009). Plasma was a preferable sample for this purpose in NK/T-cell lymphoma, nasal type, and EBV-DNA level was a good indicator for response and overall survival.

scholarly journals Pretreatment EBV-DNA Copy Number Is Predictive of Response and Toxicities to SMILE Chemotherapy for Extranodal NK/T-cell Lymphoma, Nasal Type

2012 ◽  
Vol 18 (15) ◽  
pp. 4183-4190 ◽  
Author(s):  
Yoshinori Ito ◽  
Hiroshi Kimura ◽  
Yoshinobu Maeda ◽  
Chizuko Hashimoto ◽  
Fumihiro Ishida ◽  
...  
Keyword(s):  
T Cell ◽  
Copy Number ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Dna Copy Number ◽  
Nasal Type ◽  
Ebv Dna ◽  
Nk T Cell

scholarly journals Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Free Survival

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

scholarly journals Mitochondrial DNA copy number in peripheral blood: a potential non-invasive biomarker for female subfertility

2018 ◽  
Vol 35 (11) ◽  
pp. 1987-1994 ◽  
Author(s):  
Andrea Busnelli ◽  
Debora Lattuada ◽  
Raffaella Rossetti ◽  
Alessio Paffoni ◽  
Luca Persani ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Peripheral Blood ◽  
Copy Number ◽  
Dna Copy Number ◽  
Non Invasive ◽  
Mitochondrial Dna Copy Number

scholarly journals 1792. Viral DNA Loads in Various Blood Components of Patients with EBV-Positive T/NK Cell Lymphoproliferative Diseases

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S660-S661
Author(s):  
Jun-ichi Kawada ◽  
Yasuko Kamiya ◽  
Akihisa Sawada ◽  
Keiji Iwatsuki ◽  
Koji Izustu ◽  
...  
Keyword(s):  
Disease Activity ◽  
Infectious Mononucleosis ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Inactive Disease ◽  
Blood Component ◽  
Blood Components ◽  
Ebv Dna

Abstract Background Epstein–Barr virus (EBV) is associated with T- and NK-cell lymphoproliferative disorders (EBV T/NK-LPD). For diagnosis of EBV T/NK-LPD, quantification of EBV DNA loads in peripheral blood by real-time PCR has been widely used. However, optimal blood components and cut-off values for diagnosis were not fully evaluated. Methods Fifty-nine patients with EBV T/NK-LPD including chronic active EBV infection (CAEBV), severe mosquito bite allergy, hydroa vacciniforme-like lymphoproliferative disorder (HV), and EBV- hemophagocytic lymphohistiocytosis (EBV-HLH) were enrolled. EBV DNA loads were compared among disease categories in each blood component from the same whole blood sample. The association between EBV DNA loads and disease activity were evaluated in CAEBV patients. Furthermore, the diagnostic cut-off value for EBV DNA loads in whole blood from CAEBV patients as compared with infectious mononucleosis patients was determined. Results EBV DNA loads in whole blood and peripheral blood mononuclear cells (PBMCs) were not significantly different among disease categories, whereas EBV DNA loads in plasma were significantly higher in EBV- HLH patients than in HV patients. EBV DNA loads in whole blood and PBMCs showed strong correlation (Figure 1). EBV DNA loads in plasma were significantly higher in CAEBV patients with active disease than in those with inactive disease (median: 104.5 IU/mL vs. 100.8 IU/mL, P < 0.001) (Figure 2). Diagnostic cut-off values for whole blood EBV DNA loads of CAEBV patients as compared with those of infectious mononucleosis was 104.2 ( = 15,800) IU/mL (Figure 3). Conclusion Measuring EBV DNA loads in whole blood can be considered as initial evaluation for diagnosis of EBV T/NK-LPD. EBV DNA loads in plasma are more closely related to disease activity of CAEBV than EBV DNA loads in whole blood and PBMCs. Disclosures All authors: No reported disclosures.

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