BIOTHERAPY OF CHRONIC MYELOGENOUS LEUKEMIA

The aim of this review is to summarize the current knowledge on the clinical results of biotherapy of chronic myelogenous leukemia (CML) and potential mechanisms of the antitumor action of interferon alpha. IFN alpha treatment induces hematologic and cytogenetic remissions in patients with chronic phase CML. In addition, the duration of the chronic phase is prolonged by IFN alpha resulting in a significant survival benefit. In two randomized clinical trials this survival benefit was demonstrated in all chronic phase CML patients independent of their risk scores. Moreover, IFN treatment also delays the onset of clinical relapse after allogeneic bone marrow transplantation. The critical mechanisms of IFN action have not yet been identified. Both direct and indirect antiproliferative mechanisms have been described. In particular, differential regulation of growth promoting and growth inhibiting cytokines represents an attractive hypothetical mechanism of IFN action. Nevertheless, no leukemia specific IFN activities explaining cytogenetic remissions and/or delay of disease progression have been identified. Further research on that field are required to further improve biological CML therapies.