Interferon-α-Induced Biologic Modifications in Patients with Chronic Myelogenous Leukemia

Abstract

Serum neopterin (Np), (β₂-microglobulin (β2-M), and 2′,5′-adenylate (2′,5′A) levels and intracellular 2′,5′A and human Mx (Hu-Mx) protein synthesis were measured in 20–24 chronic myeloid leukemia patients before and during 1 year of IFN-α treatment and in a further 8–9 patients before and at the end of the first and second treatment weeks only. Univariate analysis showed that IFN-α increased Np and 2′,5′A serum levels and intracellular concentrations of 2′,5′A and Hu-Mx significantly from the end of the first week to month 12 of therapy. The biologic marker profiles were similar in cytogenetic responders and nonresponders, as well as in patients treated with IFN-α early (<12 months from diagnosis) or late (after >12 months standard chemotherapy). Further, there were no differences in the short-term (first 14 days) or long-term (during 12 month therapy) induction of the biologic markers irrespective of whether IFN-α_2a or IFN-α_2b, was given. Because multivariate analysis revealed no significant interactions between cytogenetic response, time to treatment, and type of IFN-α used, increments in intracellular 2′,5′A and Hu-Mx protein were similar at all study times for all factor combinations tested. Np levels varied significantly only during the first 14 therapy days; changes in serum 2′,5′A were never statistically significant. Discrepancies between univariate and multivariate analyses for the last two markers, with respect to intracellular 2′,5′A and Hu-Mx protein, may have been a result of the small number of observations for each factor combination, a less marked induction of these two molecules, and the diversity of their values in single patients.