title: Cessation of immunosuppression during chemotherapy for post-transplant lymphoproliferative disorders in renal transplant patients.
abstract: BACKGROUND
  The optimal reduction of immunosuppressive therapy (IST) in renal transplant patients with post-transplant lymphoproliferative disorders (PTLDs) is uncertain. As chemotherapy is immunosuppressive, IST may be stopped during this time without compromising graft function. Subsequent long-term reduction of IST reduces relapse risk, but may increase risk of graft rejection.
  
  
  METHODS
  We performed a retrospective, matched cohort study of adult renal transplant patients in whom IST was ceased during chemotherapy and resumed at lower dose (calcineurin inhibitor at 50%, prednisolone ≤10 mg daily, no third agent) approximately 6 weeks after chemotherapy. Outcomes were compared with those of renal transplant patients without PTLD, matched for creatinine at equivalent time post-transplant that PTLD was diagnosed in cases, as well as for age, gender and year of transplant.
  
  
  RESULTS
  Twenty-four cases of PTLD occurring at a median of 9.2 years post-transplant were compared with 83 matched controls. PTLD cases were followed for a median of 11.9 years. Using competing risks analysis, time to 25% increase in serum creatinine was not significantly different between the two groups [adjusted hazard ratio (HR) 1.8, 95% confidence interval (CI) 0.89-3.6]. Similar results were obtained using multivariable Cox regression analysis (HR 1.19, 95% CI 0.44-3.23). Only one PTLD case experienced a ≥25% increase in creatinine <6 months after IST cessation in the setting of progressive PTLD and death. Three cases recommenced dialysis, compared with three controls (HR 2.5, 95% CI 0.47-13.00). Five-year patient survival rates for cases and controls were 70 and 94%, respectively (P = 0.01).
  
  
  CONCLUSIONS
  IST can be safely ceased during chemotherapy for PTLD in renal transplant patients. Furthermore, long-term reduction in IST is not associated with a significant difference in renal function deterioration. Prospective trials are needed to address the optimal reduction of IST in PTLDs.
authors.affiliation: Department of Haematology, Pathology Queensland and Cancer Services, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Taylor
authors.affiliation: School of Population Health, University of Queensland, Brisbane, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Jones
authors.affiliation: Department of Haematology, Pathology Queensland and Cancer Services, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hourigan
authors.affiliation: Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia Translational Research Institute, University of Queensland, Brisbane, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.affiliation: Department of Haematology, Pathology Queensland and Cancer Services, Princess Alexandra Hospital, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Devinder S
authors.initials: DS
authors.lastname: Gill
authors.affiliation: Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Isbel
authors.affiliation: Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Carmel M
authors.initials: CM
authors.lastname: Hawley
authors.affiliation: Department of Haematology, Pathology Queensland and Cancer Services, Princess Alexandra Hospital, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Paula
authors.initials: P
authors.lastname: Marlton
authors.affiliation: Department of Haematology, Pathology Queensland and Cancer Services, Princess Alexandra Hospital, Brisbane, Australia Diamantina Institute, University of Queensland, Brisbane, Australia.
authors.forename: Maher K
authors.initials: MK
authors.lastname: Gandhi
authors.affiliation: Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Campbell
authors.affiliation: Department of Haematology, Pathology Queensland and Cancer Services, Princess Alexandra Hospital, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Mollee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006801:Humans; D007108:Immune Tolerance; D016867:Immunocompromised Host; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008232:Lymphoproliferative Disorders / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents
keywords: PTLD; graft function; graft survival; immunosuppression; renal transplant