Incidence, Risk Factors, Clinical Management, and Outcomes of Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients

Abstract

Background: Posttransplant lymphoproliferative disorder (PTLD) is a severe complication after kidney transplantation. This study examined the incidence, risk factors, clinical management, and outcomes of PTLD in a cohort of kidney transplant recipients. Design: This single-center cohort study included 1642 patients transplanted from January 1, 2000, to December 31, 2012, with follow-up until December 31, 2013. The incidence and risk factors for PTLD were examined using a Cox proportional hazards model. A Cox model was also used to assess the association of PTLD and graft outcomes. Results: Sixteen recipients developed PTLD over follow-up. The incidence rate was 0.18 (95% confidence interval [CI]: 0.11-0.29) cases per 100 person-years. Four were from Epstein-Barr virus (EBV) mismatched (Dþ/RÀ) transplants and 12 from EBV-positive recipients (Rþ). Recipients with Dþ/RÀ matches were at a significantly higher risk of developing PTLD than Rþ (hazard ratio [HR]: 7.52 [95% CI: 2.42-23.32]). Fifteen cases had immunosuppression reduced, 11 cases were supplemented with rituximab or ganciclovir, 6 cases required chemotherapy or radiation, and 6 cases had tumors excised. By the end of follow-up, 6 patients went into remission, 5 returned to chronic dialysis, and 5 patients died. Patients with PTLD were significantly more likely to have total graft failure (return to chronic dialysis, preemptive retransplant, or death with graft function) than patients without PTLD (HR: 3.41 [95% CI: 1.72-6.78). Discussion: Epstein-Barr virus mismatch continues to be a strong risk factor for developing PTLD after kidney transplantation. Recipients with PTLD have a poor prognosis, as the optimal management remains to be elucidated.

Outcomes of kidney retransplantation in recipients with prior posttransplant lymphoproliferative disorders: An analysis of the 2000–2019 UNOS/OPTN database

“…Finally, due to the nature of this database study, information was unavailable on EBV viral clearance prior to retransplantation, EBV virus screening practices after retransplantation, changes in immunosuppression overtime, cumulative dose of immunosuppression regimen, and adjunctive uses of antiviral prophylaxis agents. Furthermore, data on poor prognostic factors among PTLD patients such as monoclonality, primary CNS involvement, multiple involved locations, tumor originated from T cell, high international prognostic index (IPI) scores, and number of extranodal locations were unavailable 10,11,49‐51 . Thus, these study's results should be cautiously interpreted.…”

“…Furthermore, when compared to patients without a history of PTLD, we found no increased risks of death‐censored graft failure, mortality, and acute rejection after retransplantation among those with prior PTLD. Advances in monitoring and the treatment of PTLD including reduction of immunosuppression, rituximab therapy either in isolation or in combination with other chemotherapeutic agents, adoptive therapy, surgical intervention, antiviral therapy, and radiotherapy have been hypothesized to play a significant role in improving clinical outcomes among PTLD patients over the last two decades 1,10,42‐48 …”

“…Posttransplant lymphoproliferative disease (PTLD) is one of the most serious and potentially fatal complications after both bone marrow and solid organ transplantation with an incidence range in the first 10 years after transplantation of 0.8% to 2.5% in kidney transplant recipients 1‐10 . These disorders range from lymphoid hyperplasia to highly invasive malignant lymphoma, and can be life‐threatening with mortality rates up to 60% in patients with rapidly progressive and aggressive forms of the disease 2,11‐13 .…”

Cost burden of post-transplant lymphoproliferative disease following kidney transplants in Medicare-eligible patients by survival status

“…Post-transplant lymphoproliferative disease (PTLD) is an aggressive type of lymphoma that can develop following allogeneic hematopoietic cell transplant (HCT) or solid organ transplant (SOT) [1,2]. Only patients post-transplant are at risk of PTLD and it is regarded as rare in the posttransplant population [1,3].…”

“…Only patients post-transplant are at risk of PTLD and it is regarded as rare in the posttransplant population [1,3]. Patients who have had a transplant are severely immunocompromised due to use of immunosuppressive agents and have a substantially higher risk (between 1.5 and 2.2 times) of developing a lymphoma after transplant (PTLD), compared with the general population [2,4,5]. While HCT patients can receive immunosuppressants for up to 5 years after a transplant, SOT patients with a functioning transplant need to remain immunosuppressed for the rest of their lives to prevent allograft rejection and are therefore at risk of PTLD throughout their lives [1,6,7].…”