Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients

Blood ◽  
2001 ◽  
Vol 97 (5) ◽  
pp. 1165-1171 ◽  
Author(s):  
Servi J. C. Stevens ◽  
Erik A. M. Verschuuren ◽  
Inge Pronk ◽  
Wim van der Bij ◽  
Martin C. Harmsen ◽  
...  
Keyword(s):  
Whole Blood ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Serum Samples ◽  
Barr Virus ◽  
Load Monitoring ◽  
Risk Patients ◽  
Posttransplant Lymphoproliferative Disease ◽  
Ebv Dna ◽  
Epstein Barr

Posttransplant lymphoproliferative disease (PTLD) is a frequent and severe Epstein-Barr virus (EBV)–associated complication in transplantation recipients that is caused by iatrogenic suppression of T-cell function. The diagnostic value of weekly EBV DNA load monitoring was investigated in prospectively collected unfractionated whole blood and serum samples of lung transplantation (LTx) recipients with and without PTLD. In PTLD patients, 78% of tested whole blood samples were above the cut-off value of quantitative competitive polymerase chain reaction (Q-PCR) (greater than 2000 EBV DNA copies per mL blood), with the majority of patients having high viral loads before and at PTLD diagnosis. Especially in a primary EBV-infected patient and in patients with conversion of immunosuppressive treatment, rapid increases in peripheral blood EBV DNA load diagnosed and predicted PTLD. In non-PTLD transplantation recipients, only 3.4% of the whole blood samples was above the cut-off value (P < .0001) despite heavy immune suppression and cytomegalovirus (CMV)-related disease. These findings illustrate the clinical importance of frequent EBV DNA load monitoring in LTx recipients. The increased EBV DNA loads in PTLD patients were restricted to the cellular blood compartment, as parallel serum samples were all below cut-off value, which indicates absence of lytic viral replication. EBV+ cells in PTLD patients have a very short doubling time, which can be as low as 56 hours, thereby creating the need for high screening frequency in high-risk patients. Furthermore, it is shown that EBV and CMV can reactivate independently in LTx recipients and that EBV DNA load monitoring may be useful in discriminating PTLD from rejection.

scholarly journals Prevention of Epstein-Barr virus–lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4364-4369 ◽  
Author(s):  
Joost W. J. van Esser ◽  
Hubert G. M. Niesters ◽  
Bronno van der Holt ◽  
Ellen Meijer ◽  
Albert D. M. E. Osterhaus ◽  
...  
Keyword(s):  
High Risk ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Viral Reactivation ◽  
Preemptive Therapy ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Risk Patients ◽  
Ebv Dna ◽  
Epstein Barr

Recipients of a partially T-cell–depleted (TCD) allogeneic stem cell transplantation (allo-SCT) developing reactivation of Epstein-Barr virus (EBV) with quantified viral DNA levels exceeding 1000 genome equivalents/milliliter (geq/mL) are at high risk for EBV–lymphoproliferative disease (EBV-LPD). We studied whether preemptive therapy with rituximab prevents EBV-LPD, LPD-mortality, and abrogates viral reactivation in high-risk patients. We monitored 49 recipients of a TCD allo-SCT weekly for EBV reactivation by quantitative real-time polymerase chain reaction (PCR). Preemptive therapy by a single infusion of rituximab was given to patients with viral reactivation more than or equal to 1000 geq/mL. Results were compared with an historical control group of patients retrospectively monitored for EBV reactivation at similar intervals. There were 17 prospectively monitored patients who showed EBV reactivation more than or equal to 1000 geq/mL and 15 received preemptive therapy. Median time to preemptive therapy was 113 days (range, 41-202 days) after SCT. There were 14 patients who showed complete response (CR) as characterized by prevention of EBV-LPD and complete clearance of EBV-DNA from plasma, which was achieved after a median number of 8 days (range, 1-46 days). One patient progressed to EBV-LPD despite pre-emptive therapy, but obtained CR after 2 infusions of rituximab and donor lymphocyte infusion. There were 2 patients who had already developed EBV-LPD prior to preemptive rituximab, but obtained CR following 2 rituximab infusions. Comparison of this prospectively followed series to our historical cohort with the same high-risk profile showed a reduction of EBV-LPD incidence (18% ± 9% versus 49% ± 11%, respectively) and a complete abrogation of LPD-mortality (0% versus 26% ± 10%, respectively) (P = .04) at 6 months from EBV-DNA more than or equal to 1000 geq/mL. Frequent quantitative monitoring of EBV reactivation and preemptive therapy by rituximab improves outcome in patients at high risk of EBV-LPD.

Prospective Study of Tailoring Whole-Body Dual-Modality [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography With Plasma Epstein-Barr Virus DNA for Detecting Distant Metastasis in Endemic Nasopharyngeal Carcinoma at Initial Staging

2013 ◽  
Vol 31 (23) ◽  
pp. 2861-2869 ◽  
Author(s):  
Lin-Quan Tang ◽  
Qiu-Yan Chen ◽  
Wei Fan ◽  
Huai Liu ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Epstein Barr Virus ◽  
Distant Metastases ◽  
Emission Tomography ◽  
Barr Virus ◽  
Positron Emission ◽  
Pet Ct ◽  
Risk Patients ◽  
Ebv Dna ◽  
Epstein Barr

Purpose To evaluate which patients with nasopharyngeal carcinoma (NPC) obtained the greatest benefits from the detection of distant metastasis with [18F]fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT) combined with plasma Epstein-Barr virus (EBV) DNA levels. Patients and Methods Consecutive patients with NPC were prospectively enrolled. PET/CT, conventional work-up (CWU), and quantification of plasma EBV DNA were performed before treatment. The accuracy of these strategies for distant metastases was assessed. The costs of the diagnostic strategies were compared. Results Eighty-six (14.8%) of the 583 eligible patients were found to have distant metastases; 71 patients (82.6%) by PET/CT and 31 patients (36.0%) by CWU. In the multivariable analysis, advanced N stage (odds ratio, 2.689; 95% CI, 1.894 to 3.818) and pretreatment EBV DNA level (odds ratio, 3.344; 95% CI, 1.825 to 6.126) were significant risk factors for distant metastases. PET/CT was not superior to CWU for detecting distant metastases in very low–risk patients (N0-1 with EBV DNA < 4,000 copies/mL; P = .062), but was superior for the low-risk patients (N0-1 with EBV DNA ≥ 4,000 copies/mL and N2-3 with EBV DNA < 4,000 copies/mL; P = .039) and intermediate-risk patients (N2-3 disease with EBV DNA ≥ 4,000 copies/mL; P < .001). The corresponding patient management changes based on PET/CT were 2.9%, 6.3%, and 16.5%, respectively. The costs per true-positive case detected by PET/CT among these groups were ¥324,138 (≈$47,458), ¥96,907 (≈$14,188), and ¥34,182 (≈$5,005), respectively. Conclusion PET/CT detects more distant metastases than conventional staging in patients with NPC. The largest benefit in terms of cost and patient management was observed in the subgroup with N2-3 disease and EBV DNA ≥ 4,000 copies/mL.

scholarly journals Epstein-Barr Virus–Positive Posttransplant Lymphoproliferative Disease After Solid Organ Transplantation

2016 ◽  
Vol 2 (1) ◽  
pp. e48 ◽  
Author(s):  
Marieke L. Nijland ◽  
Marie José Kersten ◽  
Steven T. Pals ◽  
Frederike J. Bemelman ◽  
Ineke J.M. ten Berge
Keyword(s):  
Organ Transplantation ◽  
Epstein Barr Virus ◽  
Solid Organ Transplantation ◽  
Lymphoproliferative Disease ◽  
Solid Organ ◽  
Barr Virus ◽  
Posttransplant Lymphoproliferative Disease ◽  
Epstein Barr

scholarly journals Establishment of a Screening Method for Epstein-Barr Virus-Associated Gastric Carcinoma by Droplet Digital PCR

2019 ◽  
Vol 7 (12) ◽  
pp. 628 ◽  
Author(s):  
Takuya Shuto ◽  
Jun Nishikawa ◽  
Kanami Shimokuri ◽  
Ayaka Yanagi ◽  
Tatsuya Takagi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Epstein Barr Virus ◽  
Screening Method ◽  
Complete Agreement ◽  
Quantitative Detection ◽  
Serum Samples ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Background: Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is classified as one of the molecular subtypes of gastric cancer. We used droplet digital polymerase chain reaction (ddPCR) to enable highly sensitive and quantitative detection of EBV. Methods: EBV-DNA load was calculated based on the copy number of the BamH1-W fragment of EBV by ddPCR, and the cut-off value of EBV-DNA load was set. We conducted both ddPCR and EBER1 ISH to examine whether their results coincided in 158 gastric cancer specimens of unknown EBV status. We prepared 26 biopsy specimens and 49 serum samples including EBVaGC and assayed them by ddPCR. Results: The median values of EBV-DNA load for EBVaGC and EBV-negative control were 17.0 and 0.00308, respectively. A cut-off value of 0.032 was determined for which the sensitivity was 1. Among the 158 gastric cancer specimens, 14 lesions were judged as EBV-positive by the 0.032 cut-off value determined by ddPCR. The results of ddPCR and EBER1 ISH were in complete agreement. Even when using a biopsy specimen as a sample for ddPCR, the EBV-DNA load of all EBVaGCs was larger than the cut-off value. Conclusions: We established a new method of diagnosing EBVaGC from tissue samples by ddPCR.

scholarly journals Epstein‐Barr Virus (EBV) Early‐Antigen Antibodies and EBV DNA Load in Blood, in Posttransplantation Lymphoproliferative Disease

2004 ◽  
Vol 190 (8) ◽  
pp. 1524-1525 ◽  
Author(s):  
Marianne Leruez‐Ville ◽  
Cécile Talbotec ◽  
Frank Iserin ◽  
Rémi Salomon ◽  
Florence Lacaille ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Early Antigen ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr
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