Post-transplantation Lymphoproliferative Disease

Wheless, Stephen A.; Gulley, Margaret L.; Raab‐Traub, Nancy; McNeillie, Patrick; Neuringer, Isabel P.; Ford, H. James; Aris, Robert M.

doi:10.1164/rccm.200804-531oc

Cited by 40 publications

(10 citation statements)

References 28 publications

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“…The presence of Epstein Barr virus (EBV) affects 90% of the world's population, with immunity to EBV present in the majority of adults [1], and thus the majority of donor organs are EBV positive [2]. Those who are EBV naïve at the time of transplant are more likely to acquire an infection from the donor and progress through primary EBV infection to viral transformation of naïve B cells, resulting in posttransplant lymphoproliferative disease (PTLD) [3]. Conditions such as plasma cell hyperplasia and primary EBV infection may be viewed as manifestations of potential PTLD, while polymorphic PTLD, monomorphic PTLD, B cell neoplasms, T cell neoplasms, and classical Hodgkin lymphoma constitute neoplastic processes as recently reviewed [4].…”

Section: Introductionmentioning

confidence: 99%

Posttransplant Lymphoproliferative Disease after Lung Transplantation

Neuringer

2013

Clinical and Developmental Immunology

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Posttransplant lymphoproliferative disease (PTLD) after lung transplantation occurs due to immunosuppressant therapy which limits antiviral host immunity and permits Epstein-Barr viral (EBV) replication and transformation of B cells. Mechanistically, EBV survives due to latency, escape from cytotoxic T cell responses, and downregulation of host immunity to EBV. Clinical presentation of EBV may occur within the lung allograft early posttransplantation or later onset which is more likely to be disseminated. Improvements in monitoring through EBV viral load have provided a means of earlier detection; yet, sensitivity and specificity of EBV load monitoring after lung transplantation may require further optimization. Once PTLD develops, staging and tissue diagnosis are essential to appropriate histopathological classification, prognosis, and guidance for therapy. The overall paradigm to treat PTLD has evolved over the past several years and depends upon assessment of risk such as EBV-naïve status, clinical presentation, and stage and sites of disease. In general, clinical practice involves reduction in immunosuppression, anti-CD20 biologic therapy, and/or use of plasma cell inhibition, followed by chemotherapy for refractory PTLD. This paper focuses upon the immunobiology of EBV and PTLD, as well as the clinical presentation, diagnosis, prognosis, and emerging treatments for PTLD after lung transplantation.

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Section: Introductionmentioning

confidence: 99%

Posttransplant Lymphoproliferative Disease after Lung Transplantation

Neuringer

2013

Clinical and Developmental Immunology

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“…Of course, this is in concert with balancing the risk of allograft rejection. In the management of EBV-associated PTLD, the control of the EBV infection may or may not play a pivotal role, but antiviral therapy has been advocated by some centers [7]. European best practice guidelines recommend the use of antivirals for at least 1 month after the diagnosis of PTLD [8].…”

Section: Discussionmentioning

confidence: 99%

“…Acyclovir, valganciclovir, or ganciclovir are first-line therapeutic recommendations. When monitoring the EBV PCR values in association with PTLD, the DNA levels generally fall within 2 weeks and become undetectable by reducing immunosuppression and initiating antiviral therapy [7, 9]. Patients have been reported to have peak plasma EBV DNA PCR levels of 663,000 copies/mL [9].…”

Section: Discussionmentioning

confidence: 99%

Use of Foscarnet Therapy for EBV Infection following Control of PTLD with Enhancement of Cellular Immunity in a Lung-Transplant Recipient

Afshar

Rao

Patel

et al. 2011

Journal of Transplantation

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Posttransplant lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation with an annual incidence rate of 3–5% in lung-transplant recipients. Pathogenesis indicates a strong association with functional over-immunosuppression and EBV infection. Clinical improvement is generally observed with reduction in immunosuppression intensity alone. We present a case of a 24-year-old woman with EBV-associated PTLD following lung transplant where decreasing the immunosuppression improved PTLD but was ineffective against controlling the EBV infection. Foscarnet in combination with immunoglobulins was successfully administered to cause a remission of the EBV infection. This is the second case reported of a persistent EBV infection after reducing immunosuppression levels and evidence of PTLD remission that required foscarnet for EBV infection control.

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“…With increasing availability of nucleic acid testing (NAT) methods, measuring EBV DNA in blood has proven valuable in diagnosing and monitoring PTLD [16,21,22,37-41], NPC [42,43], IM [13,44], EBV infection in HIV-infected individuals [8,13,45], BL [13] and chronic active EBV infection [18,46]. In this study, we successfully developed two in-house QPCR methods incorporating a novel single quantification standard containing two EBV DNA targets for measuring viral load on the Rotor-Gene 6000™.…”

Section: Discussionmentioning

confidence: 99%

Measurement of Epstein-Barr virus DNA load using a novel quantification standard containing two EBV DNA targets and SYBR Green I dye

Lay

Lucas

Ratnamohan

et al. 2010

Virol J

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BackgroundReactivation of Epstein-Barr virus (EBV) infection may cause serious, life-threatening complications in immunocompromised individuals. EBV DNA is often detected in EBV-associated disease states, with viral load believed to be a reflection of virus activity. Two separate real-time quantitative polymerase chain reaction (QPCR) assays using SYBR Green I dye and a single quantification standard containing two EBV genes, Epstein-Barr nuclear antigen-1 (EBNA-1) and BamHI fragment H rightward open reading frame-1 (BHRF-1), were developed to detect and measure absolute EBV DNA load in patients with various EBV-associated diseases. EBV DNA loads and viral capsid antigen (VCA) IgG antibody titres were also quantified on a population sample.ResultsEBV DNA was measurable in ethylenediaminetetraacetic acid (EDTA) whole blood, peripheral blood mononuclear cells (PBMCs), plasma and cerebrospinal fluid (CSF) samples. EBV DNA loads were detectable from 8.0 × 102 to 1.3 × 108 copies/ml in post-transplant lymphoproliferative disease (n = 5), 1.5 × 103 to 2.0 × 105 copies/ml in infectious mononucleosis (n = 7), 7.5 × 104 to 1.1 × 105 copies/ml in EBV-associated haemophagocytic syndrome (n = 1), 2.0 × 102 to 5.6 × 103 copies/ml in HIV-infected patients (n = 12), and 2.0 × 102 to 9.1 × 104 copies/ml in the population sample (n = 218). EBNA-1 and BHRF-1 DNA were detected in 11.0% and 21.6% of the population sample respectively. There was a modest correlation between VCA IgG antibody titre and BHRF-1 DNA load (rho = 0.13, p = 0.05) but not EBNA-1 DNA load (rho = 0.11, p = 0.11).ConclusionTwo sensitive and specific real-time PCR assays using SYBR Green I dye and a single quantification standard containing two EBV DNA targets, were developed for the detection and measurement of EBV DNA load in a variety of clinical samples. These assays have application in the investigation of EBV-related illnesses in immunocompromised individuals.

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Post-transplantation Lymphoproliferative Disease

Abstract: EBV DNA levels are a useful but imperfect predictor of PTLD in patients with lung transplants. Pretransplant EBV status affected the results of the assay and should be considered when interpreting test results. HLA-A3 was strongly linked to PTLD and may be a novel marker of PTLD risk.

Cited by 40 publications

References 28 publications

Posttransplant Lymphoproliferative Disease after Lung Transplantation

Posttransplant Lymphoproliferative Disease after Lung Transplantation

Use of Foscarnet Therapy for EBV Infection following Control of PTLD with Enhancement of Cellular Immunity in a Lung-Transplant Recipient

Measurement of Epstein-Barr virus DNA load using a novel quantification standard containing two EBV DNA targets and SYBR Green I dye

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