Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity?

Leblond, Véronique; Davi, Frédéric; Charlotte, Frédéric; Dorent, Richard; Bitker, Marc‐Olivier; Sutton, Laurent; Gandjbakhch, I; Binet, Jacques‐Louis; Raphaël, Martine

doi:10.1200/jco.1998.16.6.2052

Cited by 336 publications

(252 citation statements)

References 34 publications

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“…In heart recipients, mortality from lymphoma was even higher -50% in the first year -and no improvement in survival was noted between patients transplanted recently or earlier ( Figure 8B). Contrary to claims in the literature (22,23,28,29) the time to development of lymphoma did not prognosticate survival in kidney or heart recipients. Five-year survival was 41.4% (n = 125) and 37.0% (n = 575) for kidney recipients whose tumors developed in <90 days or >365 days, respectively (p = NS); the corresponding 5-year survival rates in heart recipients were 33.3% (n = 42) and 30.0% (n = 398) (p = NS).…”

Section: Patient Survivalcontrasting

confidence: 99%

“…Several reports have suggested differences between the clinical and biological characteristics of lymphomas that develop early or late after transplantation. Late-appearing lymphomas frequently lack EBV genome sequences, were reported to respond poorly to reduction or discontinuation of immunosuppression, and generally are believed to have a poorer outcome (22,23,28,29). In contrast to these reports, our data suggest that lymphomas have a poor outcome regardless of time of appearance after transplantation.…”

Section: Lymphomas After Solid Organ Transplantationcontrasting

confidence: 86%

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Lymphomas After Solid Organ Transplantation: A Collaborative Transplant Study Report

Opelz

Döhler

2004

American Journal of Transplantation

977

787

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We used the Collaborative Transplant Study database to analyze the incidence, risk, and impact of malignant lymphomas in approximately 200 000 organ transplant recipients. Over a 10-year period, the risk in renal transplant recipients was 11.8-fold higher than that in a matched nontransplanted population (p < < 0.0001). The majority of lymphomas were diagnosed after the first post-transplant year. Heart-lung transplants showed the highest relative risk (RR 239.5) among different types of organ transplants. In kidney recipients, immunosuppression with cyclosporine did not confer added risk compared with azathioprine/steroid treatment, whereas treatment with FK506 increased the risk approximately twofold. Induction therapy with OKT3 or ATG, but not with anti-IL2 receptor antibodies, increased the risk of lymphoma during the first year. Antirejection therapy with OKT3 or ATG also increased the risk. First-year mortality in renal and heart transplant patients with lymphoma was approximately 40% and 50%, respectively, and showed no improvement in recent years. A pattern of preferential localization to the vicinity of the transplant was noted, and the prognosis of the patient was related to localization. This study highlights the continuing risk for lymphoma with time post-transplantation, the contribution of immunosuppression to increased risk, and continuing poor outcomes in patients with post-transplant lymphoma.

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Section: Patient Survivalcontrasting

confidence: 99%

Section: Lymphomas After Solid Organ Transplantationcontrasting

confidence: 86%

Lymphomas After Solid Organ Transplantation: A Collaborative Transplant Study Report

Opelz

Döhler

2004

American Journal of Transplantation

977

787

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“…The occasional EBV-negative PTLD occurs later (usually Ͼ2 years) after transplant and does not respond as well to withdrawal of immunosuppression. 24,25 PTLD-like tumors occasionally occur in patients who have not undergone transplant but who are immunosuppressed for other reasons, such as rheumatoid arthritis patients on methotrexate therapy. 26 As with PTLD, these tumors are often EBER-positive and respond favorably to immune reconstitution.…”

Section: Eber In Situ Hybridizationmentioning

confidence: 99%

Molecular Diagnosis of Epstein-Barr Virus-Related Diseases

Gulley

2001

The Journal of Molecular Diagnostics

294

237

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Epstein-Barr virus (EBV) is the causative agent of in-fectious mononucleosis, and it may also be found in a wide variety of benign and malignant lesions including oral hairy leukoplakia, inflammatory pseudotumor, Hodgkin's disease, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. Molecular testing is increasingly important in the diagnosis and monitoring of patients affected by these diseases. In biopsy tissues, molecular detection of EBV-encoded RNA transcripts by in situ hybridization remains the gold standard for proving that a histopathological lesion is EBV-related. EBV-encoded RNA hybridization and EBV LMP1 immunostains are used routinely to detect latent EBV in tissues affected by posttransplant lymphoproliferative disorder (PTLD) or in enlarged nodes from patients with infectious mononucleosis. Traditional serology is the best test for evaluating acute versus remote infection in healthy individuals. High serological titers serve as a tumor marker for some EBV-related malignancies, but titers are not a dependable tumor marker in immunocompromised hosts. EBV viral load testing by quantitative DNA amplification of blood samples is a promising new laboratory test that has proven useful for early diagnosis and monitoring patients with PTLD. Recent studies suggest a role for EBV viral load testing in nasopharyngeal carcinoma, Hodgkin's disease, and AIDS patients with brain lymphoma. Further research is needed to define more fully the clinical utility of viral load tests in the full spectrum of EBV-associated diseases. Gene expression profiling is on the horizon as a means to improve subclassification of EBV-related diseases and to predict response to therapy. In subsequent decades, EBV has been linked to a wide variety of benign and neoplastic diseases. Nasopharyngeal carcinomas and posttransplant lymphoproliferative disorders are nearly always EBV-associated, whereas several other tumors, such as Hodgkin's disease, nonHodgkin's lymphoma, lymphoepithelioma-like carcinoma, gastric adenocarcinoma, and several types of sarcoma, are less uniformly EBV-associated. 2-7 EBV causes benign transient lymphoproliferative lesions at the time of primary infection, and it is found in a benign lesion of the tongue called oral hairy leukoplakia. 8,9 Patients affected by these benign or malignant diseases may benefit from laboratory detection of EBV to confirm their diagnosis or to monitor disease burden after the initiation of therapy.Laboratory detection of EBV is accomplished in several ways (Table 1), and recent progress has focused on the molecular analysis of viral DNA and RNA. In situ hybridization has long been considered the gold standard for detecting tumor-associated viral infection, and EBV viral load assays are now being adopted for clinical evaluation of tumor burden in affected patients. This review article summarizes the pathobiology of EBV infection and describes the clinical laboratory tests that are used to assist in diagnosis and monitoring of patients with EBV-related diseases. The ...

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“…Unlike post-transplant LPD, where $90% of the lesions contain evidence of EBV [1] about two-thirds of LPD in patients with rheumatologic disease are EBVnegative [14]. One author suggested that those cases of post-transplant LPD not associated with EBVare a distinct entity with poor outcome [15] The clinical picture of the presenting symptoms of LPD in children receiving chemotherapy for malignancy is quite variable, depending on the site of involvement (Table I). However, acute illness and extranodal organ involvement have been shared features in both the reported patients and the girl presented here.…”

Section: Discussionmentioning

confidence: 99%

“…There was no family record of familial malignancy or immunodeficiency. The girl was treated according to the ALL-BFM-95 standard risk protocol and remission was achieved on day 15. Week four of chemotherapy was complicated by severe pancreatitis, which was thought to be due to L-asparaginase.…”

Section: Introductionmentioning

confidence: 99%

B‐Cell lymphoproliferative disorder not associated with Epstein‐Barr Virus in a child with relapsed acute lymphoblastic leukemia

Lehrnbecher

Trusen

Deinlein

et al. 2002

Med. Pediatr. Oncol.

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Lymphoproliferative disorder (LPD) is described in only a few children receiving chemotherapy for cancer. In all of them, an association between LPD and EBV (Epstein‐Barr Virus) was found. We report on a patient who developed LPD not associated with EBV while receiving chemotherapy for relapsed acute lymphoblastic leukemia (ALL). Despite discontinuation of chemotherapy, administration of intravenous immunoglobulins and surgery the patient died. Growing experience with this disorder may allow better treatment options in the future and will show whether LPD not associated with EBV requires different therapeutic strategies. Med Pediatr Oncol 2003;40:13–17, © 2003 Wiley‐Liss, Inc.

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Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity?

Cited by 336 publications

References 34 publications

Lymphomas After Solid Organ Transplantation: A Collaborative Transplant Study Report

Lymphomas After Solid Organ Transplantation: A Collaborative Transplant Study Report

Molecular Diagnosis of Epstein-Barr Virus-Related Diseases

B‐Cell lymphoproliferative disorder not associated with Epstein‐Barr Virus in a child with relapsed acute lymphoblastic leukemia

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