Chronic high Epstein-Barr virus load carrier state and risk for late onset PTLD/malignant lymphoma

Bingler, Michael; Miller, Susan A.; Boyle, G.J.; Michaels, Marian G.; Green, M.; Wadowsky, Robert M.; Rowe, David; Morell, Victor O.; Quivers, Eric S.; Webber, Steven A.

doi:10.1016/j.healun.2004.11.242

Cited by 3 publications

(4 citation statements)

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“…The observation that primary EBV infection after organ transplantation in children is associated with sustained virus detection is consistent with our own experience in children undergoing many types of solid organ transplantation 6, 8, 9. There are some limitations to the present study.…”

supporting

confidence: 87%

“…It is worth noting that many of our children developed the high‐load carrier state after experiencing complete recovery from an episode of EBV disease or PTLD. Among our pediatric heart transplant recipients, we observed that 6 (30%) of 20 patients with persistently high loads subsequently developed late de novo PTLD (including monomorphic disease/Burkitt's lymphoma), and 3 others developed recurrent polymorphic disease 9. In contrast, only 1 of 32 patients who carried high loads among our pediatric liver transplant recipients have gone on to develop PTLD or lymphoma in association with a persistent high load carrier state (unpublished data).…”

mentioning

confidence: 78%

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Persistent increased Epstein-Barr virus loads after solid organ transplantation: Truth and consequences?

Green

Webber

2007

Liver Transpl

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supporting

confidence: 87%

mentioning

confidence: 78%

Persistent increased Epstein-Barr virus loads after solid organ transplantation: Truth and consequences?

Green

Webber

2007

Liver Transpl

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“…In fact it is well established that persistence of EBV is a risk factor for development of lymphomas 27. Moreover a recent study on paediatric heart transplant recipients has shown that chronically high EBV viral load carrier state is a risk factor for developing PTLD 28. This implies that a methodical pre‐emptive approach will be particularly helpful to avoid late‐onset PTLD in this setting.…”

Section: Discussionmentioning

confidence: 99%

Sustained Epstein-Barr virus detection in paediatric liver transplantation. Insights into the occurrence of late PTLD

et al. 2007

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Epstein-Barr virus (EBV) infection is the main cause of post-transplant lymphoproliferative disease (PTLD). Little is known on chronic carrier state and its relation with late PTLD. We aimed to study EBV infection in the long-term after paediatric liver transplantation (OLT). We conducted a retrospective review of 34 children monitored for a median of 5.8 years (range 1.5-17.7). 21 were IgG seronegative (group A) and 13 seropositive (group B) before OLT. Primary infection was the appearance of VCA-IgM or VCA-IgG or Real-Time Polymerase Chain Reaction (RT-PCR) in patients previously IgG seronegative; positive VCA-IgM or EA-IgG or RT-PCR lasting longer than 6 months was defined sustained viral detection (SVD). 18/21 patients of group A had a primary infection at a median time of 3 months after transplant (0.5-60). 14/18 of group A and 0/13 of group B had a SVD (P Ͻ 0.0001). Viral loads greater than 500 copies/10 5 mononuclear cells occurred in 12/18 patients in group A and 0/13 patients in group B (P Ͻ 0.0001). The 3 patients who developed late PTLD (median time after OLT 47 months, range 15-121) were from group A, and presented with SVD before developing PTLD. In conclusion, EBV infection in seronegative patients at OLT is associated with greater viral loads and sustained viral detection. Late PTLD occurred only in naïve patients with markers of SVD. Three to 4 monthly long-term monitoring of EBV in pre-OLT naïve patients might help preventing the occurrence of late PTLD. Liver Transpl 13: [343][344][345][346][347][348] 2007 See Editorial on Page 321Epstein-Barr virus (EBV) is a ubiquitous herpes virus, with a prevalence in adult subjects of more than 90%. The infection resolves without complications in immunocompetent hosts as cellular immune response takes control of the virus, but can originate a lymphoproliferative disorder in patients with no efficacious cellular immunity. 1,2 Post-transplant lymphoproliferative disease (PTLD) is a well known complication of EBV infection, which affects both bonemarrow and solid organ transplant recipients. 3 PTLD most often occurs following a EBV primary infection acquired after transplant and has a high morbidity and mortality. Because of the young age, about 50% of paediatric liver transplant candidates are EBVseronegative at the time of listing, making PTLD a major threat in these patients. 4 PTLD can present in the first few months or later after liver transplantation (OLT). 5,6 Finding risk factors for occurrence of PTLD can allow to react on time to the event. Despite new tools for the diagnosis of EBV infection have proven helpful for the pre-emptive approach to PTLD, 7,8 information on late-onset disease are lacking in this setting. We wondered whether, in which patient and for how long EBV monitoring should be performed in the long-term, and whether the follow up schedule adopted for transplanted children is adequate to pick up late EBV-related complications. We therefore performed a retrospective study on markers Abbreviations: EBV, Epstein-Barr virus; RT-PCR, re...

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“…Negative EBV serologic status prior to transplantation and primary EBV infection post‐transplant have been identified as risk factors for development of PTLD [8,9]. Elevated EBV DNA load has been linked to the development of late‐onset PTLD in children after HTX or bone marrow transplantation [10–12]. Using quantitative real‐time polymerase chain reaction (PCR), it is possible to monitor EBV DNA load in peripheral blood.…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus load in whole blood is associated with immunosuppression, but not with post-transplant lymphoproliferative disease in stable adult heart transplant patients

Doesch

Konstandin

Celik

et al. 2008

Transplant International

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Summary Development of Epstein‐Barr virus (EBV)‐associated post‐transplant lymphoproliferative disease (PTLD) is a serious complication following heart transplantation (HTX). This study investigates EBV DNA load in adult heart transplant recipients, its association with immunosuppression, and its potential as a marker for development of PTLD. EBV DNA load was measured prospectively by quantitative real‐time polymerase chain reaction (PCR) in 172 stable HTX patients. Sixty‐seven patients (39.0% of total) had a positive EBV PCR at initial examination [median 4.9 (range 1.1–16.9) years post‐HTX]. In follow‐up testing of 67 positive patients 6 months later, 36 patients continued to have a positive EBV PCR. Overall incidence of EBV DNA was significantly associated with calcineurin inihibitors, azathioprine medication, and with the absence of mycophenolate mofetil (MMF) treatment. In patients with positive EBV DNA levels at initial examination and negative levels at retesting, cyclosporine A levels were found to be significantly higher at initial examination (148.4 ± 70.2 vs. 119.6 ± 53.5 ng/ml, P < 0.05). Three patients (1.7%, 3/172) were diagnosed with PTLD during the course of the study (mean follow up 4.0 years). EBV DNA viral load determination does not appear to be useful for risk prediction or early diagnosis of PTLD in adults after HTX, but an association of EBV DNA load with qualitative and quantitative immunosuppression is demonstrated.

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Chronic high Epstein-Barr virus load carrier state and risk for late onset PTLD/malignant lymphoma

Cited by 3 publications

References 0 publications

Persistent increased Epstein-Barr virus loads after solid organ transplantation: Truth and consequences?

Persistent increased Epstein-Barr virus loads after solid organ transplantation: Truth and consequences?

Sustained Epstein-Barr virus detection in paediatric liver transplantation. Insights into the occurrence of late PTLD

Epstein-Barr virus load in whole blood is associated with immunosuppression, but not with post-transplant lymphoproliferative disease in stable adult heart transplant patients

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