Malignancy in Renal Transplant Recipients Exposed to Cyclophosphamide Prior to Transplantation for the Treatment of Native Glomerular Disease.

Abstract

To evaluate the risk of posttransplantation malignancy in renal transplant recipients exposed to pretransplantation cyclophosphamide for the treatment of glomerular nephropathy (GN). Retrospective cohort study. Tertiary academic medical center. Six hundred adult renal transplant recipients were transplanted between 1993 and 2014; 54 patients were exposed to pretransplantation cyclophosphamide for treatment of GN (GN-CYC group), and 546 patients with polycystic kidney disease were not exposed to pretransplantation cyclophosphamide (PKD group). Data were collected retrospectively from electronic medical records. The primary outcome was occurrence of posttransplantation malignancy. During a median follow-up of 5.5 years, 130 patients developed malignancy (incidence rate 3.5 events per 100 person-yrs). Exposure to cyclophosphamide before transplantation was significantly associated with malignancy after transplantation (adjusted hazard ratio [aHR] 2.20, 95% confidence interval [CI] 1.16-4.22, p=0.02), specifically skin cancer (aHR 2.24, 95% CI 1.09-4.60, p=0.03). Malignancy risk in the GN-CYC group was higher in the setting of lymphocyte-depleting induction (alemtuzumab; aHR 4.53, 95% CI 0.99-20.72, p=0.05) compared with basiliximab induction. Incidences of death-censored graft loss and mortality were similar between the GN-CYC and PKD groups. In our observational study, renal transplant recipients exposed to pretransplantation cyclophosphamide appeared to have a higher risk of developing a malignancy compared with unexposed renal transplant recipients. Further investigation into the impact of pretransplantation immunosuppression on malignancy, particularly the compounded effect with lymphocyte-depleting induction, is warranted.