High incidence of autoimmune alterations in chronic myeloid leukemia patients treated with interferon-alpha

Interferon-alpha is the frontline therapy of the majority of chronic myeloid leukemia (CML) patients who are not eligible for bone marrow transplantation. Many patients are treated for long periods, and there is concern about the long-term immune effects of its use. Autoimmune disorders in patients treated with IFN-alpha may be related to the direct immunomodulating properties of IFN or may be linked to a possible toxic effect in target organs, triggering autoimmunity. On the other hand, the immune effects of IFN may play a role in its therapeutic actions. The aims of our study were to assess the incidence of autoimmune phenomena in these patients, and to measure the possible association between the generation of autoimmune phenomena and the antileukemic effect of IFN alpha. Therefore, 46 patients with Ph1(+) CML in the first chronic phase were studied for the appearance of immune complications, their connection to IFN dose, time of appearance, and the possible association with the response to treatment. Autoimmune abnormalities have been found in 28% of our patients. Moreover, a significant association was found between autoimmune alterations and female sex (P = 0.02, OR 4.5, 95% CI 1.13-17.9) and a longer treatment time (1.6 vs. 4.1 years) (P = 0.02; OR 1.01, 95% CI 1-1.02). The Kaplan-Meier estimated probability of obtaining a cytogenetic response was significantly higher in patients who developed autoimmune alterations (P = 0.049), and this difference was also evident in Cox's analysis when controlling with other potentially confounding variables (P = 0.078). We conclude that CML patients treated with IFN alpha have a high incidence of autoimmune phenomenon.