Association of Immunosuppressive Maintenance Regimens With Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients

Sampaio, Marcelo Santos; Cho, Yong W.; Shah, Tariq; Bunnapradist, Suphamai; Hutchinson, Ian V.

doi:10.1097/tp.0b013e31823ae7db

Cited by 78 publications

(55 citation statements)

References 35 publications

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“…The median follow-up time was five years (range 3 to 10 years). The observed rate of PTLD was 0.98% overall and 0.93% in kidney transplant patients, broadly comparable to published reports in the transplant population overall [10]. The studies included in the analysis did not, however, permit comparisons with no induction or other types of induction agent since few were designed to compare rATG therapy with other regimens.…”

Section: Pooled Datasupporting

confidence: 78%

“…The risk of developing PTLD is organspecific, with higher rates of both PTLD [8] and NHL [9] following heart, lung and intestinal transplantation where higher doses of immunosuppression are required. An analysis of over 100,000 patients receiving a primary kidney transplant during 2000-2009 found the five-year incidence of PTLD to be 0.84% [10], compared to N1.0% in heart transplant patients [11]. Recipients of a lung or heart-lung transplant are at the highest risk due to the lymphoid-rich nature of lung tissue and importation of high levels of EBV from the donor.…”

Section: Epidemiology and Risk Factorsmentioning

confidence: 98%

“…Widespread adoption of calcineurin inhibitor (CNI) therapy was associated with a significant increase in risk of NHL [23,24]. CNI agents are almost universally prescribed, at least in the immediate posttransplant period, with some evidence suggesting a higher risk for PTLD under tacrolimus versus cyclosporine [10,25]. Mycophenolate mofetil (MMF) does not appear to affect risk for PTLD [24,26].…”

Section: The Role Of Immunosuppressive Therapiesmentioning

confidence: 98%

See 2 more Smart Citations

Rabbit antithymocyte globulin induction and risk of post-transplant lymphoproliferative disease in adult and pediatric solid organ transplantation: An update

Hertig

Zuckermann

2015

Transplant Immunology

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The most modifiable risk factor for post-transplant lymphoproliferative disease (PTLD) is the type and dose of induction and maintenance immunosuppressive therapy. It is challenging to identify the contribution of a single agent such as rabbit antithymocyte globulin (rATG) in the setting of multidrug therapy. Registry analyses can be helpful but are limited by methodological restrictions and inclusion of historical patient cohorts. These are typically from eras when rATG dosing was markedly higher than current dosing (e.g. total dose 14 mg/kg versus 6 mg/kg now), accompanied by higher exposure to maintenance therapies, and often an absence of antiviral prophylaxis. The largest registry analysis to assess rATG specifically found no risk of PTLD after kidney transplantation, but conflicting results have been reported, highlighting the difficulty of interpreting this type of analysis. The relative rarity of PTLD means that individually controlled trials are underpowered to assess its occurrence, but the available data do not suggest an effect of rATG. A pooled analysis of data from studies of rATG induction in kidney and heart transplantation found the incidence of PTLD to be comparable to published reports in the overall transplant population. Data on the effect of rATG dose are inconclusive, but in patients receiving antiviral prophylaxis it does not appear to be influential. Nevertheless, it would seem reasonable to employ the lowest dose of rATG compatible with effective induction, particularly in EBV-seronegative recipients and other high-risk groups such as heart-lung transplant recipients. Overall, the risk of PTLD following rATG induction therapy with modern dosing regimens and under current management conditions appears unlikely to make an important contribution to the risk:benefit balance.

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Section: Pooled Datasupporting

confidence: 78%

Section: Epidemiology and Risk Factorsmentioning

confidence: 98%

Section: The Role Of Immunosuppressive Therapiesmentioning

confidence: 98%

See 1 more Smart Citation

Rabbit antithymocyte globulin induction and risk of post-transplant lymphoproliferative disease in adult and pediatric solid organ transplantation: An update

Hertig

Zuckermann

2015

Transplant Immunology

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“…These centers identified PTLD predominantly in older patients with an underlying diagnosis of COPD, as well as equally distributed between those with COPD, IPF, Eisenmengers, and alpha-1 antitrypsin deficiency [9, 11]. Immunosuppressant regimens may impact upon the development of PTLD, as recent reports from kidney transplantation cite an increased risk of PTLD in patients receiving mTOR inhibitors and tacrolimus compared to patients receiving cyclosporin and mycophenolate mofetil [27]. To date, few studies in the lung transplant literature have cited clear PTLD risk with distinct immunosuppressant regimens, other than overall immunosuppressant load and use of induction therapy.…”

Section: Clinical Presentation Of Ptld After Lung Transplantationmentioning

confidence: 99%

Posttransplant Lymphoproliferative Disease after Lung Transplantation

Neuringer

2013

Clinical and Developmental Immunology

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Posttransplant lymphoproliferative disease (PTLD) after lung transplantation occurs due to immunosuppressant therapy which limits antiviral host immunity and permits Epstein-Barr viral (EBV) replication and transformation of B cells. Mechanistically, EBV survives due to latency, escape from cytotoxic T cell responses, and downregulation of host immunity to EBV. Clinical presentation of EBV may occur within the lung allograft early posttransplantation or later onset which is more likely to be disseminated. Improvements in monitoring through EBV viral load have provided a means of earlier detection; yet, sensitivity and specificity of EBV load monitoring after lung transplantation may require further optimization. Once PTLD develops, staging and tissue diagnosis are essential to appropriate histopathological classification, prognosis, and guidance for therapy. The overall paradigm to treat PTLD has evolved over the past several years and depends upon assessment of risk such as EBV-naïve status, clinical presentation, and stage and sites of disease. In general, clinical practice involves reduction in immunosuppression, anti-CD20 biologic therapy, and/or use of plasma cell inhibition, followed by chemotherapy for refractory PTLD. This paper focuses upon the immunobiology of EBV and PTLD, as well as the clinical presentation, diagnosis, prognosis, and emerging treatments for PTLD after lung transplantation.

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“…Risk of PTLD has been associated with EBV donor positive/ recipient negative individuals, those with higher levels of EBV DNA detection, chronic HVL, detectable DNA in plasma and those receiving T cell depleting antibodies (7,8,23,(33)(34)(35)(36). Preemptive strategies to reduce PTLD incidence include reduction of immunosuppression, and more recently, the use of rituximab in transplant patients with persistent high-level DNAemia.…”

Section: Bamoulid Et Al Holman Et Al and Holmes Et Al Reported Ebvmentioning

confidence: 99%

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Morton¹,

Coupes²,

Roberts

et al. 2014

American Journal of Transplantation

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Epstein-Barr virus (EBV) DNAemia in the first year posttransplantation has been studied extensively. There is a paucity of information on prevalence and sequelae of EBV infection in adult renal transplantation beyond the first year. This single-center study examines the relationship between EBV DNAemia and demographic, immunosuppressive, hematologic and infection-related parameters in 499 renal transplant recipients between 1 month and 33 years posttransplant. Participants were tested repeatedly for EBV DNAemia detection over 12 months and clinical progress followed for 3 years. Prevalence of DNAemia at recruitment increased significantly with time from transplant. In multivariate adjusted analyses, variables associated with DNAemia included EBV seronegative status at transplant (p ¼ 0.045), nonWhite ethnicity (p ¼ 0.014) and previous posttransplant lymphoproliferative disease (PTLD) diagnosis (p ¼ 0.006), while low DNAemia rates were associated with mycophenolate mofetil use (p < 0.0001) and EBV viral capsid antigen positive Epstein-Barr nuclear antigen-1 positive serostatus at transplant (p ¼ 0.044). Patient and graft survival, rate of kidney function decline and patient reported symptoms were not significantly different between EBV DNAemia positive and negative groups. EBV DNAemia is common posttransplant and increases with time from transplantation, but EBV DNAemia detection in low-risk (seropositive) patients has poor specificity as a biomarker for future PTLD risk.

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Association of Immunosuppressive Maintenance Regimens With Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients

Abstract: In EBV- recipients, immunosuppression with mTORi+TAC was associated with increased risk of PTLD, death, and graft failure, while MMF+CsA use was associated with a trend to increased risk of rejection, lower PTLD risk, and similar risk for graft failure when compared with MMF+TAC.

Cited by 78 publications

References 35 publications

Rabbit antithymocyte globulin induction and risk of post-transplant lymphoproliferative disease in adult and pediatric solid organ transplantation: An update

Rabbit antithymocyte globulin induction and risk of post-transplant lymphoproliferative disease in adult and pediatric solid organ transplantation: An update

Posttransplant Lymphoproliferative Disease after Lung Transplantation

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

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