Immune-mediated complications during interferon alpha therapy in chronic myelogenous leukemia

Several prospective randomized studies have shown that the treatment of chronic myeloid leukemia with interferon alpha (IFNalpha) prolongs the survival by comparison with conventional chemotherapy. However, long-term treatment with Interferon alpha can produce or exacerbate immune-mediated complications (IMC). The purpose of this study was to analyze the experience with IMC in patients with chronic myelogenous leukemia (CML) undergoing IFNalpha treatment. The occurrence of IMC was evaluated in 76 patients (47 male; 29 female) with Philadelphia chromosome (Ph)-positive CML. Diagnostic criteria of IMC were performed in patients with symptoms suggestive of particular disorders. Well-documented and clinically evident complications developed in 7 patients after a median of 19 months (range 1-84) of IFNalpha treatment. These included 9.2% patients with Ph-positive CML treated with IFNalpha-containing regimens. Hypothyroidism (H) occurred in 1 patient (1.3%), immune-mediated hemolysis (HEM) in 2 patients (2.6%) and connective tissue disorders (CTD) in 4 patients (5.3%) (2 systemic lupus erythematosus--SLE, 1 Raynaud's phenomena and 1 mixed connective tissue disease--MCTD). IFNalpha was discontinued in 3 patients and the dose was reduced in 2 patients. Five of 7 patients (75%) with immune-mediated complications had some degree of cytogenetic response at the time of the event. The association with female sex was strong and significant (86% vs 33.6%, x2; 48; p = 0.02). The frequency of IMC of clinical relevance with interferon alpha therapy in CML increased (long-term therapy). The patients treated with interferon alpha should be monitored for signs and symptoms of autoimmunity.