Alpha-interferon-associated thrombotic microangiopathy - A clinicopathologic study of 8 patients and review of the literature

Alpha-interferon (α-IFN) has been used to treat various hematologic malignancies for the last 2 decades. Hemolytic uremic syndrome-like nephropathy has rarely been reported as a specific toxicity. We report 8 cases of thrombotic microangiopathy (TMA) in patients treated with α-IFN for chronic myelogenous leukemia (CML). They received high doses of α-IFN (mean ± standard error of the mean [SEM], 39.1 ± 7.1 MU/wk) for a prolonged time (mean ± SEM, 32.1 ± 7.9 mo). At time of diagnosis the mean proteinuria and serum creatinine were 4.2 ± 1.3 g/d and 3.0 ± 1.1 mg/dL, respectively. Renal biopsy findings showed arteriolar and glomerular lesions consistent with TMA. It is noteworthy that symptoms of distal ischemia were observed in 5 of 8 patients: 3 complained of Raynaud phenomenon while 4 presented with severe distal necrotic lesions. Elevated serum anticardiolipin antibodies were not detected. Alpha-IFN treatment was rapidly discontinued in 7 cases. Intensive therapy did not prevent the decline of renal function in 2 patients, who required dialysis. These 8 patients, together with the 21 previously published cases, confirm the association of α-IFN treatment and TMA. Our review underlines several characteristics of this association. TMA occurs after a prolonged and high-dose treatment, in striking contrast with the other α-IFN-related nephropathies. TMA is mainly associated with CML patients. Ischemic cutaneous lesions are frequently observed. The occurrence of moderate to severe renal failure is usually associated with a poor renal prognosis.