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

Transpl Int. 2014 Sep;27(9):956-65. doi: 10.1111/tri.12375. Epub 2014 Aug 20.

Abstract

Post-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.

Keywords: calcineurin inhibitor; graft survival; immunosuppression withdrawal; kidney transplant; post-transplant lymphoproliferative disorder.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Calcineurin Inhibitors / administration & dosage
  • Calcineurin Inhibitors / adverse effects*
  • Calcineurin Inhibitors / therapeutic use
  • Creatine / blood
  • Drug Substitution
  • Epstein-Barr Virus Infections / etiology*
  • Epstein-Barr Virus Infections / mortality
  • Epstein-Barr Virus Infections / pathology
  • Epstein-Barr Virus Infections / therapy
  • Female
  • France / epidemiology
  • Glomerular Filtration Rate
  • Graft Rejection / epidemiology
  • Graft Rejection / etiology
  • Graft Rejection / prevention & control
  • Graft Survival
  • Humans
  • Immunocompromised Host
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Kidney / physiopathology
  • Kidney Transplantation*
  • Lymphoproliferative Disorders / etiology*
  • Lymphoproliferative Disorders / mortality
  • Lymphoproliferative Disorders / pathology
  • Lymphoproliferative Disorders / therapy
  • Male
  • Middle Aged
  • Pancreas Transplantation
  • Postoperative Complications / etiology*
  • Postoperative Complications / mortality
  • Postoperative Complications / pathology
  • Postoperative Complications / therapy
  • Proportional Hazards Models
  • Radiotherapy, Adjuvant
  • Renal Dialysis
  • Renal Insufficiency / etiology
  • Renal Insufficiency / mortality
  • Renal Insufficiency / therapy
  • Retrospective Studies
  • Risk Factors
  • Rituximab
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Rituximab
  • Creatine