Quantitative Assessment of the Impact of Interferon Alpha (IFN) vs. Busulfan vs. Hydroxyurea and of Risk Profile on Survival in Chronic Myelogenous Leukemia (CML)

All randomized studies have shown that IFN prolongs life as compared to conventional chemotherapies. The prolongation of survival varies between 11 and 21 months. As an example, the updated German CML Study I (IFN vs. hydroxyurea vs. busulfan, median observation time 70.4 months) is shown [significant survival advantage of IFN over busulfan (p = 0.007) and of hydroxyurea over busulfan (p = 0.05), but not of IFN over hydroxyurea (p = 0.24)]. The increment of survival by therapy in all studies is small. Overall survival differs between studies and depends on patient selection, phase of CML in which IFN therapy is started, strategy of IFN therapy (monotherapy or IFN combinations) and intensity of treatment with hydroxyurea. If studies are ranked according to risk profile, those with a higher proportion of good risk patients observe longer overall survival. If stratified for risk profile, survival differences, in analyzed instances, disappeared. Additional information gained from a comparison of the protocols of the German and Italian randomized studies shows that IFN is most effective in patient populations that 1. include early asymptomatic cases, 2. exclude cases with more than 10% circulating blasts or extramedullary manifestations and, 3. exclude patients older than 70 years.