CYCLOPHOSPHAMIDE AS AN ALTERNATIVE TO AZATHIOPRINE IN CARDIAC TRANSPLANT RECIPIENTS WITH SUSPECTED AZATHIOPRINE-INDUCED HEPATOTOXICITY

AZA has been reported to cause liver dysfunction in some recipients of solid organ transplants. To assess the safety and efficacy of cycloph osphamide in maintenance immunosuppression in the setting of AZA-induc ed liver dysfunction, we retrospectively reviewed the records of 320 s urviving cardiac transplant recipients in Utah. Cyclophosphamide was s ubstituted for AZA in 29 patients due to elevated liver enzymes. Patie nts were switched to cyclophosphamide 689+/-104 days after transplanta tion; total follow-up after initiation of cyclophosphamide was 540+/-5 6 days. The dose of cyclophosphamide after 2 and 6 months of cyclophos phamide therapy was 62+/-6 mg/day (0.8+/-0.1 mg/kg/day) and 48+/-5 mg/ day (0.62+/-0.1 mg/kg/day), respectively, compared with 233+/-20 mg/da y (2.9+/-0.2 mg/kg/day) of AZA. The substitution of cyclophosphamide f or AZA was associated with a significant improvement in liver function tests. Liver enzymes decreased by up to 49% (P=0.027), while serum bi lirubin decreased by 58% (P<0.001). Rejection frequency did not increa se; neither corticosteroid nor CsA dosage was altered significantly af ter the substitution of cyclophosphamide. Significant bone marrow supp ression was not observed; specifically, no significant change in white blood cell count or hematocrit occurred. Complications of treatment w ith cyclophosphamide were few; only 1 patient discontinued cyclophosph amide because of alopecia. We conclude that cyclophosphamide appears t o be safe in maintenance immunosuppression, permitting the discontinua tion of AZA in patients with AZA-induced hepatic dysfunction without n ecessitating the augmentation of either corticosteroids or CsA.