Maintaining calcineurin inhibition after the diagnosis of post-transplant lymphoproliferative disorder improves renal graft survival

Serre, Jean-Emmanuel; Michonneau, David; Bachy, Emmanuel; Nôël, Laure-Hélène; Dubois, Valérie; Suberbielle, Caroline; Kreis, Henri; Legendre, Christophe; Mamzer-Bruneel, Marie-France; Morélon, Emmanuel; Thaunat, Olivier

doi:10.1038/ki.2013.253

Cited by 35 publications

(27 citation statements)

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“…Lastly, in this series, the precise cause of graft loss was known for only 17% of patients (biopsies were performed in five patients who experienced graft loss; this rate of biopsy is similar to that performed in other studies) . Furthermore, our findings cannot be extended to pediatric patients.…”

Section: Discussionsupporting

confidence: 67%

“…Another study showed that rituximab combined with RI (but without chemotherapy) was ineffective in prevention of acute rejection (45% ). Additionally, a recent publication suggested that the maintenance of CNI at a reduced dose appeared to be associated with a lower incidence of de novo anti‐HLA antibodies and better control of the humoral response of the recipient . Despite the risk of rejection, short‐term renal function for patients with PTLD receiving RI, rituximab, and chemotherapy was similar to that of a control population .…”

Section: Discussionmentioning

confidence: 99%

“…Serre et al [22] found that maintaining CNI at reduced dose after PTLD is safe and may improve renal graft outcome but did not appear to affect overall survival. In this study, patient survival was influenced by the International Prognosis Index (IPI) and the use of rituximab but not by the type of immunosuppressive regimen and the PTLD staging as independent factor was not analyzed.…”

Section: Discussionmentioning

confidence: 99%

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CNI withdrawal for post-transplant lymphoproliferative disorders in kidney transplant is an independent risk factor for graft failure and mortality

et al. 2014

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SummaryPost-transplantation lymphoproliferative disorders (PTLD) are associated with poor patient and graft survival. The risk of rejection and subsequent graft loss are increased by the reduction of immunosuppression therapy, the cornerstone of PTLD treatment. This multicentre, retrospective, nonrandomized cohort study includes 104 adults who developed PTLD after renal or simultaneous renal/pancreatic transplantation between 1990 and 2007. It examines the effect of calcineurin inhibitor (CNI) withdrawal on long-term graft and patient survival. At 10 years postonset of PTLD, the Kaplan-Meier graft loss rate was 43.9% and graft loss or death with functioning graft was 64.4%. Cox multivariate analysis determined risk factors of graft loss as PTLD stage greater than I-II and CNI withdrawal, and for graft loss and mortality, these remained risk factors along with age over 60 years. Type and location of PTLD, year of diagnosis, and chemotherapy regime were not independent risk factors. Multivariate analysis determined CNI withdrawal as the most important risk factor for graft loss (HR = 3.07, CI 95%: 1.04-9.09; P = 0.04) and death (HR: 4.00, CI 95%: 1.77-9.04; P < 0.001). While long-term stable renal function after definitive CNI withdrawal for PTLD has been reported, this review determined that withdrawal is associated with reduced graft and patient survival.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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CNI withdrawal for post-transplant lymphoproliferative disorders in kidney transplant is an independent risk factor for graft failure and mortality

et al. 2014

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“…Available data remain conflicting, are not conclusive, and have not evaluated an imTOR discontinuing rate after conversion for PTLD. 17,18 Despite the objective data that justify the conversion to imTOR after diagnosis of PLTD, we believe that the suitability of this strategy should be evaluated in an individualized manner, paying attention to each particular case. A constant high level of attention is needed to detect early possible complications related to the use of imTOR, which sometimes may be a diagnostic challenge.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Castillo-Eraso

Melilli²,

Cabré³

et al. 2018

Exp Clin Transplant

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Posttransplant lymphoproliferative disease represents a heterogeneous group of diseases characterized by uncontrolled proliferation of lymphocytes, favored by immunosuppression. Several risk factors for its development have been described, with Epstein-Barr virus infection being a main cause of early-onset forms and chronic antigen stimulation of donors and/or accumulated immunosuppression as key factors of later forms of lymphocyte transformation. The present clinical case presents a patient diagnosed with post transplant lymphoproliferative disease 3 years after renal transplant who had a potentially lethal complication related to conversion to inhibitors of mammalian target of rapamycin. Because clinical studies that establish the most suitable treatment are lacking, it is recommended to identify the strategy, defining possible risks versus benefits of conversion to inhibitors of mammalian target of rapamycin in cases of posttransplant lymphoproliferative disease, and to maintain a high level of surveillance in case of possible secondary effects that can be verified after their introduction. Key words: Epstein-Barr virus infection, Immunosuppression, Renal transplant IntroductionPosttransplant lymphoproliferative disease (PTLD) represents a heterogeneous group of diseases characterized by uncontrolled proliferation of lymphocytes, favored by immunosuppression. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Several risk factors for its development have been described, with infection by Epstein-Barr virus being a main cause of early-onset forms and chronic antigen stimulation of donors and/or accumulated immunosuppression as factors of later forms of lymphocyte transformation. 2 In the literature as a first-line treatment after PTLD diagnosis, in addition to specific treatments (chemoradiation, radiotherapy, and/or immunotherapy), it is recommended that either doses of calcineurin inhibitors be decreased or agent converted to inhibitors of mammalian target of rapamycin (imTOR), 10 since, with either, the reduction of immunosuppression would restore the ability of the receptor's immune system to control the uncontrolled proliferation of lymphomatous cells. 3 However, the reduction of immunosuppression is followed by complete remission only in localized and histologically less aggressive forms, with most cases requiring addition of a chemotherapy regimen (rituximab and/or cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab). 4 On the other hand, although an imTOR has an antiproliferative effect, 5 its use is not free from possible secondary effects.Here, we present a patient diagnosed with PTLD 3 years after renal transplant who developed a potentially lethal complication related to conversion to imTOR. Because clinical studies that have established the most suitable treatment are lacking, it is recommended to identify a strategy, defining possible risks versus benefits of the conversion to imTOR in cases of PTLD, and to maintain a high level of surveillance in case of possible s...

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“…This results in reduced production of interleukin 2, inhibiting T-cell proliferation. 15,16 According to the Kidney Disease Improving Global Outcomes 2009 clinical practice guidelines, the combination of tacrolimus with an antiproliferative agent, with or without corticosteroids, is the most favored first-line CNI for initial maintenance therapy. Thus, tacrolimusbased regimens are the most commonly used regimens, with 80% of initial immuno suppression and 70% of maintenance immunosup pression received by renal transplant recipients.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Jayant

Bridson

Sharma³

et al. 2017

Exp Clin Transplant

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Objectives: This review focuses on the current limited evidence of graft function and graft survival in various immunosuppressive regimens involving mammalian target of rapamycin inhibitors with or without calcineurin inhibitors. Materials and Methods: We evaluated the current literature for describing the role of mammalian target of rapamycin inhibitors as an alternative to calcineurin inhibitors by searching the PubMed, EMBASE, Cochrane, Crossref, and Scopus databases using medical subject heading terms. Results: Our detailed analyses of all relevant literature showed use of mammalian target of rapamycin inhibitor-based de novo regimens, early calcineurin inhibitor withdrawal with subsequent introduction of mammalian target of rapamycin inhibitor-based regimens, and late conversion from a calcineurin inhibitor-based regimen to mammalian target of rapamycin inhibitor-based regimens. Notably, early calcineurin inhibitor withdrawal with subsequent introduction of mammalian target of rapamycin inhibitor-based regimen seemed to be a more practical and realistic approach toward immunosuppressive treatment of renal transplant recipients. However, in view of the high rejection rate observed in these studies, it is advisable not to offer these regimens to patients with moderate to high immunologic risk. Conclusions: The present evidences suggest that treatment with mammalian target of rapamycin inhibitors allows early and substantial calcineurin inhibitor minimization. The mammalian target of rapamycin inhibitors everolimus and sirolimus are preferred due to their complementary mechanisms of action and favorable nephrotoxicity profile, which have opened the way for calcineurin inhibitor reduction/withdrawal in the early posttransplant period.

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Maintaining calcineurin inhibition after the diagnosis of post-transplant lymphoproliferative disorder improves renal graft survival

Cited by 35 publications

References 35 publications

CNI withdrawal for post-transplant lymphoproliferative disorders in kidney transplant is an independent risk factor for graft failure and mortality

CNI withdrawal for post-transplant lymphoproliferative disorders in kidney transplant is an independent risk factor for graft failure and mortality

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