Purpose: To evaluate the incidence of malignancy in kidney transplant recipients who previously received cyclophosphamide for treatment of native glomerular disease.

Methods: Single center study of adult kidney transplant recipients (KTR) with primary native disease attributable to lupus nephritis (LN) or membranous glomerulonephritis (MN) transplanted between 1/1/1993 to 12/31/2014 with documented pre-transplant receipt of cyclophosphamide. Reference group consisted of KTR with native disease due to polycystic kidney disease (PKD). Primary outcome was incidence of post–transplant malignancy.

Results: Of a total of 205 KTR with LN or MN, 28% (n=58) had documented cyclophosphamide use prior to transplant. KTR exposed to cyclophosphamide had a significantly higher incidence of malignancy compared to PKD patients (adjusted hazard ratio [aHR]=2.05; 95% CI: 1.05, 3.99) after adjustment for age, sex, race, donor status, delayed graft function, diabetes, BMI, prior transplant, transfusion, and induction therapy. In analyses stratified by induction agent, cyclophosphamide was strongly associated with malignancy in patients receiving alemtuzumab induction (aHR=10.91; 95% CI: 3.19, 37.33. P-Interaction=0.03), but not in patients receiving thymoglobulin (aHR 2.10; 95% CI: 0.57, 7.74), basiliximab (aHR 1.10; 95% CI: 0.50, 2.44), or no induction (aHR 0.54; 95% CI: 0.05, 5.53). Cyclophosphamide exposure was significantly associated with a higher risk of skin cancer (n=398; aHR 2.50; 95% CI: 1.41, 4.44), but not with non-skin cancer (n=104) or post-transplant lymphoproliferative disorder (n=12). The incidence of death-censored graft failure was similar for KTR with cyclophosphamide exposure and the reference group (3.41 and 2.67 per 100 person-years, respectively; P=0.42). The incidence of patient death was also similar (2.16 and 3.29 per 100 person-years, respectively; P=0.24).

Conclusions: Patients exposed to cyclophosphamide prior to transplant have higher rates of malignancy following transplant. This association was significantly stronger in patients receiving alemtuzumab induction. Further study of pre-transplant cumulative immunosuppressive burden, induction agent, and screening protocols to reduce malignancy rates are needed.

CITATION INFORMATION: Mills J, Jorgenson M, Fose J, Astor B, Panzer S. Long-Term Malignancy Risk in Kidney Transplant Recipients Treated with Cyclophosphamide Pre-Transplant for Native Glomerular Disease. Am J Transplant. 2017;17 (suppl 3).

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