Post-Transplantation Lymphoproliferative Disorder After Kidney Transplantation: Report of a Nationwide French Registry and the Development of a New Prognostic Score

Caillard, Sophie; Porcher, Raphaël; François, Patrice; Dantal, Jacques; Choquet, Sylvain; Dürrbach, Antoine; Morélon, Emmanuel; Moal, Valérie; Janbon, Bénédicte; Alamartine, Éric; Noble, Claire Pouteil; Morel, D.; Kamar, Nassim; Büchler, Matthias; Peraldi, Marie Noëlle; Hiesse, C; Renoult, E.; Toupance, Olivier; Rérolle, Jean Philippe; Delmas, Sylvie; Lang, Philippe; Lebranchu, Yvon; Heng, Anne Elisabeth; Rebibou, Jean Michel; Mousson, Christiane; Glotz, Denis; Rivalan, Joseph; Thierry, Antoine; Étienne, Isabelle; Moal, Marie Christine; Albano, Laetitia; Subra, J.-F.; Ouali, Nacéra; Westeel, P. F.; Delahousse, Michel; Genin, R; Ligny, Bruno Hurault de; Moulin, Anne‐Marie

doi:10.1200/jco.2012.43.2344

Cited by 121 publications

(104 citation statements)

References 27 publications

(10 reference statements)

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“…PTLDs are often extranodal, with graft, cerebral or digestive involvement [33,34]. Clinical symptoms depend on tumoral localization and are often poorly specific [2,34,35]. Other types of malignancies, especially cutaneous tumors [36] and virus-related diseases, are also more frequent in immunocompromised patients compared to the general population [3].…”

Section: Discussionmentioning

confidence: 99%

18F-FDG PET/CT for the Diagnosis of Malignant and Infectious Complications After Solid Organ Transplantation

Muller

Kessler

Caillard

et al. 2016

Nucl Med Mol Imaging

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Purpose Infection and malignancy represent two common complications after solid organ transplantation, which are often characterized by poorly specific clinical symptomatology. Herein, we have evaluated the role of 18 F-fluoro-2-deoxy-Dglucose (FDG) positron emission tomography/computed tomography (PET/CT) in this clinical setting. Methods Fifty-eight consecutive patients who underwent FDG PET/CT after kidney, lung or heart transplantation were included in this retrospective analysis. Twelve patients underwent FDG PET/CT to strengthen or confirm a diagnostic suspicion of malignancies. The remaining 46 patients presented with unexplained inflammatory syndrome, fever of unknown origin (FUO), CMV or EBV seroconversion during post-transplant follow-up without conclusive conventional imaging. FDG PET/CT results were compared to histology or to the finding obtained during a clinical/imaging follow-up period of at least 6 months after PET/CT study. Results Positive FDG PET/CT results were obtained in 18 (31 %) patients. In the remaining 40 (69 %) cases, FDG PET/CT was negative, showing exclusively a physiological radiotracer distribution. On the basis of a patient-based analysis, FDG PET/CT's sensitivity, specificity, PPV and NPV were respectively 78 %, 90 %, 78 % and 90 %, with a global accuracy of 86 %. FDG PET/CT was true positive in 14 patients with bacterial pneumonias (n = 4), pulmonary fungal infection (n = 1), histoplasmosis (n = 1), cutaneous abscess (n = 1), inflammatory disorder (sacroiliitis) (n = 1), lymphoma (n = 3) and NSCLC (n = 3). On the other hand, FDG PET/CT failed to detect lung bronchoalveolar adenocarcinoma, septicemia, endocarditis and graft-versus-host disease (GVHD), respectively, in four patients. FDG PET/CT contributed to adjusting the patient therapeutic strategy in 40 % of cases. Conclusions FDG PET/CT emerges as a valuable technique to manage complications in the post-transplantation period. FDG PET/CT should be considered in patients with severe unexplained inflammatory syndrome or FUO and inconclusive conventional imaging or to discriminate active from silent lesions previously detected by conventional imaging particularly when malignancy is suspected.

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Section: Discussionmentioning

confidence: 99%

18F-FDG PET/CT for the Diagnosis of Malignant and Infectious Complications After Solid Organ Transplantation

Muller

Kessler

Caillard

et al. 2016

Nucl Med Mol Imaging

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“…PTLD is commonly of B-cell origin [2,7,22,24]. Overall, 60-80% of total PTLD cases are found to be EBV-positive [15,25] and the incidence of EBV positivity changes slightly according to PTLD type, being higher in early than in late cases. The EBV genome is found in more than 90% of PTLD during the first year after transplantation [26].…”

Section: Ebv-related Ptldmentioning

confidence: 92%

Post-transplant lymphoproliferative disorders: From epidemiology to pathogenesis-driven treatment

et al. 2015

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Post-transplant lymphoproliferative disorders (PTLDs) represent the most severe complication of both solid organ and hematopoietic stem cell transplantation. The Epstein-Barr Virus (EBV) is the main driver of PTLD, particularly those occurring early after transplantation. EBV-driven malignancies are associated with selective expression of latent viral proteins, but uncontrolled lytic replication may favor early phases of cell transformation. Besides immunodepression, persistent immune activation and chronic inflammation play an important role in both virus reactivation and expansion of EBV-infected B cells. EBV-induced immortalization requires the expression of telomerase. TERT, the rate-limiting component of the telomerase complex, is central in the switch from the lytic to the latent viral program, and TERT inhibition induces the EBV lytic cycle and cell death. Immunotherapy and combination of EBV lytic cycle inducers with antiviral drugs are promising strategies to improve the treatment of PTLD patients. This review is aimed at providing an update on the intriguing association between EBV and PTLD, mainly focusing on cases arising after kidney and liver transplantation, which account for the vast majority of transplants.

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“…33 During the last decade, several prognostic indices have been proposed by different authors, but validation of these scores in different transplant populations has shown conflicting results, mainly due to heterogeneity in design, patient population, and treatment. 38,56,[94][95][96][97] In most series, classical factors, including higher age, advanced disease, poor performance state, elevated lactate dehydrogenase, and CNS invasion, are also associated with poor prognosis in PTLD patients. Recently, hypoalbuminemia was also established as a very strong risk factor.…”

Section: Prognostic Factors In Ptldmentioning

confidence: 99%

How I treat posttransplant lymphoproliferative disorders

Dierickx¹,

Tousseyn

Gheysens

2015

Blood

136

172

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Posttransplant lymphoproliferative disorder (PTLD) is a potentially fatal disorder arising after solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). Iatrogenically impaired immune surveillance and Epstein-Barr virus (EBV) primary infection/reactivation are key factors in the pathogenesis. However, current knowledge on all aspects of PTLD is limited due to its rarity, morphologic heterogeneity, and the lack of prospective trials. Furthermore, the broad spectrum of underlying immune disorders and the type of graft represent important confounding factors. Despite these limitations, several reviews have been written aimed at offering a guide for pathologists and clinicians in diagnosing and treating PTLD. Rather than providing another classical review on PTLD, this “How I Treat” article, based on 2 case reports, focuses on specific challenges, different perspectives, and novel insights regarding the pathogenesis, diagnosis, and treatment of PTLD. These challenges include the wide variety of PTLD presentation (making treatment optimization difficult), the impact of EBV on pathogenesis and clinical behavior, and the controversial treatment of Burkitt lymphoma (BL)-PTLD.

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Post-Transplantation Lymphoproliferative Disorder After Kidney Transplantation: Report of a Nationwide French Registry and the Development of a New Prognostic Score

Abstract: This nationwide study highlights the prognostic factors for PTLD and enables the development of a new prognostic score. After validation in an independent cohort, the use of this score should allow treatment strategies to be better tailored to individual patients in the future.

Cited by 121 publications

References 27 publications

18F-FDG PET/CT for the Diagnosis of Malignant and Infectious Complications After Solid Organ Transplantation

18F-FDG PET/CT for the Diagnosis of Malignant and Infectious Complications After Solid Organ Transplantation

Post-transplant lymphoproliferative disorders: From epidemiology to pathogenesis-driven treatment

How I treat posttransplant lymphoproliferative disorders

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