Utility of Semiquantitative Polymerase Chain Reaction for Epstein‐Barr Virus to Measure Virus Load in Pediatric Organ Transplant Recipients with and without Posttransplant Lymphoproliferative Disease

Allen, Upton; Hébert, Diane; Petric, Martin; Tellier, Raymond; Tran, Dat; Superina, Riccardo; Stephens, Derek; West, Lori J.; Wasfy, Samia; Nelson, Susan C.

doi:10.1086/321806

Cited by 51 publications

(36 citation statements)

References 17 publications

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“…Similar results have already been reported in previous studies using similar semi-quantitative EBV PCR in PBMC, where increases in viral load were not always associated with further development of EBV-LPD and, conversely, some EBV-LPD cases were not accompanied by an increase in the EBV-VL. [24][25][26][27] In a recent study by Allen et al, 36 the positive and negative predictive value of the semi-quantitative EBV PCR were 28 and 95%, respectively. In the study conducted by Lucas et al, 27 five of seven patients with EBV-LPD had levels of EBV DNA Ͼ40 000 copies/ g DNA and two of the 34 patients without EBV-LPD had levels of EBV DNA Ͼ40 000 copies/ g DNA, giving the positive and negative predictive value for this test as 71% and 94%, respectively.…”

Section: Discussionmentioning

confidence: 99%

A prospective study of Epstein–Barr virus load in 85 hematopoietic stem cell transplants

Bueltzingsloewen

Morand

Buisson

et al. 2002

Bone Marrow Transplant

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Summary:EBV viral load (EBV-VL) in PBMC was prospectively determined by semi-quantitative PCR in 85 stem cell transplants (40 genoidentical, 45 non-genoidentical) in order to characterize the kinetics of EBV-VL and to assess the ability of this measure to predict the development of EBV-induced lymphoproliferative disease (EBV-LPD). PCR was performed prior to and after transplantation. An EBV-VL Ͼ300 copies/ g DNA was chosen as the threshold for risk of developing an EBV-LPD. Two hundred and fifty-eight EBV-VL measures were evaluable. Five patients (5.9%) developed an EBV-LPD. All had an elevated EBV DNA peak level before EBV-LPD. Fifteen out of 80 recipients (18.7%) without EBV-LPD had EBV levels over 300 copies/ g DNA at least once during the follow-up. Overall, the manifestation of at least one EBV-VL over 300 copies/ g DNA during the entire follow-up demonstrated a sensitivity, specificity, positive and negative predictive value for the diagnosis of EBV-LPD of 100%, 81%, 25% and 100%, respectively. In patients without EBV-LPD, HLA incompatibility, grade уII acute GVHD and use of an unmanipulated graft were significantly associated with an EBV-VL Ͼ300 copies/ g DNA. This strategy appears sensitive for the diagnosis of EBV-LPD but its positive predictive value has to be improved in order to guide pre-emptive therapy.

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Section: Discussionmentioning

confidence: 99%

A prospective study of Epstein–Barr virus load in 85 hematopoietic stem cell transplants

Bueltzingsloewen

Morand

Buisson

et al. 2002

Bone Marrow Transplant

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“…Initially, these methods were semiquantitative and required the comparison of Southern blot or agarose gel signals with calibrated controls. 5,[16][17][18][19] Semiquantitative assays are generally imprecise and were superseded at many centers by quantitative PCRs based on co-amplification of EBV DNA and an internal calibration standard. The internal standard normalizes each reaction and overcomes the effect of PCR inhibitors (e.g.…”

Section: Risk Factors For Ptldmentioning

confidence: 99%

Preemptive diagnosis and treatment of Epstein–Barr virus-associated post transplant lymphoproliferative disorder after hematopoietic stem cell transplant: an approach in development

Weinstock

Ambrossi

Brennan

et al. 2006

Bone Marrow Transplant

103

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Hematopoietic stem cell transplant (HSCT) recipients are at risk for Epstein-Barr virus (EBV)-associated, post transplant lymphoproliferative disorder (PTLD). Studies have suggested that early treatment may improve the outcome of patients with PTLD. Thus, significant attention has been focused on PCR-based approaches for preemptive (i.e., prior to clinical presentation) diagnosis. Reports from several transplant centers have demonstrated that HSCT recipients with PTLD generally have higher concentrations of EBV DNA in the peripheral blood than patients without PTLD. However, the PCR values of patients with PTLD typically span multiple orders of magnitude and overlap significantly with values from patients without PTLD. Thus, questions remain about the sensitivity and predictive value of these assays. Preemptive strategies using rituximab and/or EBVspecific cytotoxic T lymphocytes have been evaluated in patients with elevated EBV viral loads. We review the current literature, discuss our institutional experience and identify several areas of future research that could improve the diagnosis and treatment of this life-threatening disorder in HSCT recipients. Bone Marrow Transplantation ( EBV is associated with a spectrum of clinical presentations in hematopoietic stem cell transplant (HSCT) recipients, from fever to post transplant lymphoproliferative disorder (PTLD), which arise from the outgrowth of latently infected B cells in the absence of competent immune surveillance by cytotoxic T cells. PTLDs are extremely heterogeneous, ranging from polyclonal hyperplasia to aggressive, non-Hodgkin's lymphoma. 1-3 Thus, PTLD can present with a diverse spectrum of clinical symptoms and signs, most notably a sepsis-like syndrome with rapidly progressive lymphoma or a mononucleosis-like illness with fever, enlarged tonsils and/or cervical lymphadenopathy. PTLD may involve virtually any organ system, including the central nervous system, bone marrow, intestine and lungs. The overall frequency of PTLD after allogeneic HSCT is approximately 1%. The highest incidence occurs in the first 6 months after transplant, and the vast majority of cases develop during the first year. 4 Risk factors for PTLDMultiple published studies 4-10 have identified predisposing factors for PTLD, including in vivo and in vitro T-cell depletion. In a survey of 235 transplant centers, 4 the risk factors for PTLD in the first year after transplant included: (1) unrelated or HLA-mismatched donors (relative risk (RR) ¼ 4.1), (2) T-cell depletion (RR ¼ 12.7) and (3) the use of antithymocyte globulin (ATG) (RR ¼ 6.4) or anti-CD3 monoclonal antibodies (RR ¼ 43.2) for the prophylaxis or treatment of graft rejection and/or graft-versus-host disease (GVHD). PTLD occurred in 8% of HSCT recipients with two risk factors and 22% of recipients with three risk factors. For patients more than 1 year after HSCT, the only factor associated with PTLD was chronic GVHD (RR ¼ 4).Consistent with the essential role of T cells in controlling the proliferation of latent EBV-inf...

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“…The analytic sensitivity of the assay is 1.1 copies/µL and the detection threshold is 275 genome copies/mL of whole blood. Based on extensive experience with viral load measurements in organ transplant patients (18), viral loads of ≤6000 copies/mL were classified as low, >6000 to 30,000 as low to intermediate, >30,000 to 300,000 as intermediate to high and >300,000 copies/mL as high. The viral load assays were performed in one centre (Dr Mazzulli, Mount Sinai Hospital, Toronto).…”

Section: Laboratory Measurements Virological Assaysmentioning

confidence: 99%

Correlates of Illness Severity in Infectious Mononucleosis

Odame

Khodai‐Booran

Mazzulli

et al. 2013

Paediatrics and Child Health

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INTRODUCTION:Understanding the spectrum and frequencies of Epstein-Barr virus (EBV) complications and markers of illness severity in immunocompetent patients with primary EBV infection will inform management of patients with EBV-related illnesses. OBjECTIVES: To determine the clinical and laboratory correlates of illness severity among infants, children and youth with infectious mononucleosis (IM). METHODS: Study subjects with confirmed IM were prospectively enrolled. Illness severity was assessed at baseline and at six weeks using a scoring tool. Peripheral blood viral loads served as a measure of viral burden. RESULTS: Among 32 children and young adults with IM, the median age was 16 years (range two to 24 years). 19%]). With respect to symptoms or signs that persisted to at least six weeks after illness onset, the predominant complaint was lymphadenopathy in 35% of subjects available for reassessment. Deranged liver function tests were present at presentation in up to 44% of subjects. Patients with the highest viral loads at presentation had significantly higher illness severity scores associated with fatigue (P=0.02). Other than the scores associated with fatigue, viral load values were not significantly correlated with the illness severity scores at baseline and at six weeks. CONCLUSION: In IM, viral loads are not necessarily correlated with illness severity, with the exception of fatigue. EBV-related hepatitis is common in IM, confirming the status of this virus as a relatively common cause of transient hepatitis in children and youth. This entity is not necessarily a marker of disease severity. Key Words: Epstein-Barr virus; Hepatitis; Mononucleosis; Viral loadDes corrélats de la gravité de la maladie en cas de mononucléose infectieuse

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Utility of Semiquantitative Polymerase Chain Reaction for Epstein‐Barr Virus to Measure Virus Load in Pediatric Organ Transplant Recipients with and without Posttransplant Lymphoproliferative Disease

Cited by 51 publications

References 17 publications

A prospective study of Epstein–Barr virus load in 85 hematopoietic stem cell transplants

A prospective study of Epstein–Barr virus load in 85 hematopoietic stem cell transplants

Preemptive diagnosis and treatment of Epstein–Barr virus-associated post transplant lymphoproliferative disorder after hematopoietic stem cell transplant: an approach in development

Correlates of Illness Severity in Infectious Mononucleosis

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