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

STUDY OBJECTIVE: To evaluate the risk of posttransplantation malignancy in renal transplant recipients exposed to pretransplantation cyclophosphamide for the treatment of glomerular nephropathy (GN). DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center. PATIENTS: 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). MEASUREMENT AND MAIN RESULTS: 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. CONCLUSION: 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.