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

Abstract

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.

Post-transplant lymphoproliferative disorder following kidney transplantation: a population-based cohort study

“…Our overall survival rates after PTLD diagnosis were similar or better compared with previously reported rates . Although the size of the population involved makes it difficult to draw firm conclusions, a shorter therapeutic delay is probably more significant in PTLD compared with sporadic lymphoproliferative disorders in immunocompetent patients, as reduction in immunosuppression should be instituted immediately at the mere suspicion of PTLD, while the need for further investigation is evaluated.…”

“…The risk following kidney transplantation (often poorly defined) varies between 1 and 3% , although it has been reported up to 7% . PTLD development is associated with decreased survival of both patients and grafts , 5‐year patient survival after diagnosis ranging between 37 and 65% .…”

Post‐transplant lymphoproliferative disease in lung transplantation: A nested case‐control study

“…CLAD (mostly BOS) indeed mainly developed following prior early‐onset PTLD, suggesting that reduction of immunosuppression shortly after LTx may be the culprit for subsequent CLAD development. Similar findings were demonstrated in renal transplantation, where calcineurin‐inhibitor withdrawal for PTLD was independently associated with reduced graft and patient survival . In a minority of patients CLAD preceded PTLD, which demonstrated to be almost exclusively late‐onset PTLD cases.…”

Post‐Transplant Lymphoproliferative Disorder in Kidney Transplant Recipients: A Single‐Center Experience in Japan

“…13 was already in a state of brain‐death after the surgery; therefore overly stressful chemotherapy was not performed. Meanwhile, graft survival following late‐onset PTLD appeared to be poorer than that in previous studies . IR is commonly performed as an initial treatment for PTLD because impairment of the immunological system is a major trigger of PTLD, although the rejection caused by reduction of immunosuppressive conditions remains an unresolved problem.…”

“…In fact, some patients who received IR suffered from graft loss in the present study. Rabot et al reported that calcineurin inhibitor withdrawal could adversely influence graft and patient survival . Meanwhile, RTX and CHOP chemotherapy can be effective for maintaining graft function .…”