Chronic High Epstein-Barr Viral Load State and Risk for Late-Onset Posttransplant Lymphoproliferative Disease/Lymphoma in Children

Bingler, Michael; Feingold, Brian; Miller, Susan A.; Quivers, Eric S.; Michaels, Marian G.; Green, M.; Wadowsky, Robert M.; Rowe, David; Webber, Steven A.

doi:10.1111/j.1600-6143.2007.02080.x

Cited by 147 publications

(158 citation statements)

References 11 publications

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“…A previous study at our institution did show that both early PTLD and high chronic EBV viral loads were risk factors for late-onset PTLD, including BL in our heart transplant population and for those BL patients who had chronically high viral loads before the onset of BL. 33 Although the current study was not specifically designed to assess risk factors for development of BL, these data suggest that prior PTLD and chronic high EBV-load…”

mentioning

confidence: 84%

Post‐transplant Burkitt lymphoma is a more aggressive and distinct form of post‐transplant lymphoproliferative disorder

Picarsic

Jaffe

Mazariegos

et al. 2011

Cancer

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BACKGROUND:Although the literature reports a low incidence of Burkitt lymphoma (BL) as a post‐transplant lymphoproliferative disorder (PTLD), this entity appears to be different from other monomorphic PTLDs (M‐PTLDs), both in its aggressive clinical presentation and its distinct pathologic profile.METHODS:Patients with BL, diagnosed in the post‐transplant setting, (patients aged ≤18 years) were retrieved from the pathology archives at Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center from 1982 to 2010. Clinical outcomes were obtained along with pathologic review.RESULTS:Twelve patients with pediatric BL in the post‐transplant setting (9 boys, 3 girls) were retrieved. The patients displayed a monomorphic population of small to intermediate‐sized, noncleaved, lymphoid elements with a “starry‐sky” pattern. The immunophenotype for patients available to the study was CD20+ (n = 9/10), CD10+ (n = 8/8), bcl‐6+ (n = 11/11), with a near 100% Ki‐67/MIB‐1 proliferation index (n = 7/7), and negative for TdT (n = 7/7). Most pretransplant Epstein‐Barr virus titers were negative (n = 8/10), with post‐transplant titers positive in all tested patients (n = 11), and with positive Epstein‐Barr–encoded RNA in situ hybridization in most cases (n = 9/11). The median time from transplantation to diagnosis was 52 months (range, 6‐107 months). Nine patients were currently alive after immediate antineoplastic chemotherapy, with median disease‐free time of 93 months from diagnosis (range, 2‐199 months).CONCLUSIONS:BL‐PTLD had a higher Epstein‐Barr virus incidence compared with sporadic and immunodeficiency‐associated BL and represented a distinct monomorphic PTLD. Although some M‐PTLDs can be managed less aggressively with decreased immunosuppression alone, immediate lymphoma‐specific chemotherapy was associated with a favorable outcome and was strongly recommended. Cancer 2011;. © 2011 American Cancer Society.

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mentioning

confidence: 84%

Post‐transplant Burkitt lymphoma is a more aggressive and distinct form of post‐transplant lymphoproliferative disorder

Picarsic

Jaffe

Mazariegos

et al. 2011

Cancer

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“…Asymptomatic viremia implies a heightened risk for progression to PTLD and also predicts other adverse outcomes, such as graft dysfunction, acute rejection, or late-onset PTLD (5,19,92,113). Among heart transplant recipients studied by Bingler et al, those with chronic EBV viremia were more likely to develop late-onset PTLD, occurring as long as 8.4 years after transplant (19).…”

Section: Using Ebv Levels To Predict Graft Dysfunction Rejection Ormentioning

confidence: 99%

“…A higher mean baseline EBV load correlates with heightened risk of PTLD or recurrent PTLD (7,19). Other investigators propose combining EBV DNA measurement with a complementary test, such as EBV-specific T cell enumeration as measured by a peptide tetramer or enzyme-linked immunosorbent spot, EBV serology, reverse transcription-PCR (RT-PCR) targeting EBV transcripts, cytokine gene polymorphism, ATP release, gammopathy by serum protein electrophoresis, microarray-based expression profiles, and CD20 or CD4/CD8/NK cell counts (6,10,17,25,53,107,112,117,123,151,158,166,173,177,192,207,211,213).…”

Section: Ebv Load As a Marker Of Ptldmentioning

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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“…(20,21); in AIDS-associated CNS lymphoma, CSF PCR for EBV reliably reflects response to treatment (6,22 …”

Section: Whether Ebv Was the Etiologic Agent Of Our Patient's Leukoenmentioning

confidence: 99%

EBV-Associated Leukoencephalopathy with Late Onset of Central Nervous System Lymphoma in a Kidney Transplant Recipient

Vaglio

Manenti²,

Mancini

et al. 2010

American Journal of Transplantation

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Central nervous system (CNS) lymphoma is a rare posttransplant lymphoproliferative disorder (PTLD), which usually has a poor outcome. To date, no specific conditions predisposing to this complication have been identified. We here describe the case of a renal transplant patient who was initially diagnosed as having Epstein-Barr virus (EBV)-associated leukoencephalopathy and ultimately developed EBV-positive CNS lymphoma. The patient was a young lady who, 2 years after transplantation, presented with focal neurological and electroencephalographic abnormalities and diffuse white matter lesions on brain magnetic resonance imaging. EBV-DNA was detected in the cerebrospinal fluid (CSF) by polymerase chain reaction. After acyclovir therapy and immunosuppressive drug tapering, the symptoms and electroencephalographic abnormalities subsided, and EBV-DNA disappeared from the CSF. Ten years later, a bulky cerebral mass was found. After excision, a diagnosis of EBVpositive, Hodgkin-like monomorphic B-cell PTLD was made. This case illustrates the potential pathophysiological relationships between EBV infection, leukoencephalopathy and CNS lymphoma; although a long time elapsed from the initial neurological illness to CNS lymphoma, a link between these two conditions cannot be excluded. Therefore, a careful long-term follow-up of EBV-related encephalopathy is advisable.

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Chronic High Epstein-Barr Viral Load State and Risk for Late-Onset Posttransplant Lymphoproliferative Disease/Lymphoma in Children

Cited by 147 publications

References 11 publications

Post‐transplant Burkitt lymphoma is a more aggressive and distinct form of post‐transplant lymphoproliferative disorder

Post‐transplant Burkitt lymphoma is a more aggressive and distinct form of post‐transplant lymphoproliferative disorder

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

EBV-Associated Leukoencephalopathy with Late Onset of Central Nervous System Lymphoma in a Kidney Transplant Recipient

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