title: Long-term follow-up of kidney transplant patients with posttransplant lymphoproliferative disorder: duration of posttransplant lymphoproliferative disorder-induced operational graft tolerance, interleukin-18 course, and results of retransplantation.
abstract: BACKGROUND
  Posttransplant lymphoproliferative disorder (PTLD) can be resolved in many transplant patients by the reduction or cessation of immunosuppression, after which many grafts continue to function as the result of a form of operational tolerance. When graft function deteriorates, retransplantation may be an option. Cytokines such as interleukin (IL)-10 and IL-18 may play a role in PTLD tolerance induction and tumor regression. We report long-term follow-up on the duration of graft tolerance and the course of retransplantation in a series of patients who underwent kidney transplantation and demonstrated PTLD, and in whom we were able to perform IL-18 analyses.
  
  
  RESULTS
  Patients were followed for up to 7 years after PTLD diagnosis. Treatment consisted of immunosuppression cessation with radiation therapy in cases with overt monomorphic lymphomas. All patients' PTLDs were resolved, and all patients but one (whose graft was removed) demonstrated a period of operational graft tolerance of up to 5 years. Five patients underwent retransplantation without sign of recurrence of the PTLD up to 3 years after transplantation. In the eight patients analyzed, IL-18 increased significantly during PTLD regression and follow-up in those with long-term operational tolerance.
  
  
  CONCLUSIONS
  We report on a series of patients with resolved PTLDs demonstrating long-term recurrence-free survival, of whom most experienced a long period of operational graft tolerance. IL-18 seems to play a role in the resolution of the PTLDs. Five patients underwent retransplantation with standard immunosuppression without recurrence. A previous diagnosis of PTLD should not be regarded as a contraindication for later retransplantation.
authors.affiliation: Department of Nephrology, Odense University Hospital, Odense, Denmark. S.A.Birkeland@Birkeland.dk.
authors.forename: S A
authors.initials: SA
authors.lastname: Birkeland
authors.forename: S
authors.initials: S
authors.lastname: Hamilton-Dutoit
authors.forename: K
authors.initials: K
authors.lastname: Bendtzen
mesh_terms: D003404:Creatinine / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006085:Graft Survival / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D020382:Interleukin-18 / Q000097:blood; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000453:epidemiology* / Q000209:etiology; D011183:Postoperative Complications / Q000453:epidemiology*; D012086:Reoperation; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D020382:Interleukin-18; D003404:Creatinine