Epstein-Barr Viral Load and Disease Prediction in a Large Cohort of Allogeneic Stem Cell Transplant Recipients

Aalto, Sanna; Juvonen, Eeva; Tarkkanen, Jussi; Volin, Liisa; Haario, Heikki; Ruutu, Tapani; Hedman, Klaus

doi:10.1086/522531

Cited by 57 publications

(54 citation statements)

References 26 publications

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“…Plasma or serum samples are readily obtained and widely used for diagnosing EBV-associated PTLD; however, the sensitivity seemed to be low (28,29). Several reports have revealed that whole blood, containing both cellular and humoral compartments, is better than plasma/serum when testing patients with PTLD (20,30,31). Recently, Spacek and colleagues reported that plasma is better than whole blood for the monitoring and estimation of prognosis for Hodgkin lymphoma (32).…”

Section: Discussionmentioning

confidence: 99%

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

Ito

Kimura

Maeda

et al. 2012

Clinical Cancer Research

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Purpose: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is an Epstein-Barr virus (EBV)-associated lymphoma for which a new chemotherapeutic regimen called SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) recently showed promising results.Experimental Design: The amount of EBV-DNA was prospectively measured in whole-blood and plasma samples by real-time quantitative PCR from 26 patients registered in the SMILE phase II study.Results: Before treatment, the EBV-DNA was detected in 22 samples of whole blood with a median number of 3,691 copies/mL (range: 0-1.14 Â 10 7 ), but 15 samples of plasma with a median of 867 copies/mL (range: 0-1.27 Â 10 7 ). Results of these 2 measurements of EBV-DNA well correlated (R 2 ¼ 0.994, P < 0.001). The overall response rate to SMILE was significantly higher in patients with less than 10 5 copies/mL of EBV-DNA in whole blood at enrollment (90% vs. 20%, P ¼ 0.007) and in patients with less than 10 4 copies/mL of EBV-DNA in plasma (95% vs. 29%, P ¼ 0.002). The incidence of grade 4 toxicity of SMILE other than leukopenia/neutropenia was significantly higher in patients with 10 5 copies/mL of EBV-DNA or more in whole blood (100% vs. 29%, P ¼ 0.007) than that of others and in patients with 10 4 copies/mL or more in plasma (86% vs. 26%, P ¼ 0.002). Conclusions: These findings suggest that whole blood is more sensitive for clinical use than plasma. The EBV-DNA amount in whole blood was useful for predicting tumor response, toxicity, and prognosis after SMILE chemotherapy for ENKL. Clin Cancer Res; 18(15); 4183-90. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 99%

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

Ito

Kimura

Maeda

et al. 2012

Clinical Cancer Research

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“…However, as different systems are used for different samples and patients, it is difficult to determine which EBV load value should be used to identify high-risk patients. For example, in stem cell transplantation, some authors recommend that an EBV load of > 300 copies/10 5 PBMCs is indicative of intervention [66], while others have reported that an EBV load > 50 000 copies/mL of serum predicts the development of PTLD [69]. We also proposed that an EBV load > 10 000 copies/mg PBMC DNA is Table 4.…”

Section: Post-transplant Lymphoproliferative Disordermentioning

confidence: 92%

“…Recent studies have used plasma or serum because they are readily obtained and handled. Several studies reported that quantifying cell-free EBV DNA predicted the development of PTLD [59,68,69]. However, serum or plasma samples lack cell-associated virus and therefore plasma loads are not correlated with PBMC values [70].…”

Section: Post-transplant Lymphoproliferative Disordermentioning

confidence: 99%

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Kimura

Ito

Suzuki

et al. 2008

Reviews in Medical Virology

139

142

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Because Epstein-Barr virus (EBV) is ubiquitous and persists latently in lymphocytes, simply detecting EBV is insufficient to diagnose EBV-associated diseases. Therefore, measuring the EBV load is necessary to diagnose EBVassociated diseases and to explore EBV pathogenesis. Due to the diverse biology of EBV, the significance of measuring EBV DNA and the optimal type of specimen differ among EBV-associated diseases. Recent advances in molecular technology have enabled the EBV genome to be quantitated rapidly and accurately. Real-time polymerase chain reaction (PCR) is a rapid and reliable method to quantify DNA and is widely used not only as a diagnostic tool, but also as a management tool for EBV-associated diseases. However, each laboratory currently measures EBV load with its own ''homebrew'' system, and there is no consensus on sample type, sample preparation protocol, or assay units. The EBV real-time PCR assay system must be standardised for large-scale studies and international comparisons.

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“…Preemptive therapy may include reducing immunosuppression and infusing anti-CD20 antibody or donor T cells. (110) The threshold for preemptive treatment is reported in a number of prior studies, and the success of preemption is gauged by a drop in circulating EBV DNA by at least one log unit within the first week of intervention (2,3,15,99,109,130,137,143,185,197).…”

Section: Clinical Indications For Testingmentioning

confidence: 99%

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

2010

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SUMMARYEpstein-Barr virus (EBV) DNA measurement is being incorporated into routine medical practice to help diagnose, monitor, and predict posttransplant lymphoproliferative disorder (PTLD) in immunocompromised graft recipients. PTLD is an aggressive neoplasm that almost always harbors EBV DNA within the neoplastic lymphocytes, and it is often fatal if not recognized and treated promptly. Validated protocols, commercial reagents, and automated instruments facilitate implementation of EBV load assays by real-time PCR. When applied to either whole blood or plasma, EBV DNA levels reflect clinical status with respect to EBV-related neoplasia. While many healthy transplant recipients have low viral loads, high EBV loads are strongly associated with current or impending PTLD. Complementary laboratory assays as well as histopathologic examination of lesional tissue help in interpreting modest elevations in viral load. Circulating EBV levels in serial samples reflect changes in tumor burden and represent an effective, noninvasive tool for monitoring the efficacy of therapy. In high-risk patients, serial testing permits early clinical intervention to prevent progression toward frank PTLD. Restoring T cell immunity against EBV is a major strategy for overcoming PTLD, and novel EBV-directed therapies are being explored to thwart virus-driven neoplasia.

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Epstein-Barr Viral Load and Disease Prediction in a Large Cohort of Allogeneic Stem Cell Transplant Recipients

Cited by 57 publications

References 26 publications

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

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

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

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