Results of the treatment of chronic myeloid leukemia by tyrosine kinase inhibitors alone or in combination with interferon

Chronic Myelogenous Leukemia (CML) is a hematological stem cell disorder characterized by excessive proliferation of cells of the myeloid lineage. Designed as a target therapy against BCR-ABL tyrosine kinase activity, imatinib rapidly became the gold standard therapy in CML that dramatically changed the prognosis of the disease. Because of the persistency of stem cells, the French CML Group designed a large phase III trial to explore the efficacy and tolerability of higher dose levels of imatinib and combination with interferon. Higher rate of molecular responses was achieved with the combination of imatinib and pegylated form of interferon, the dose of 45 mu g being feasible and effective. Of interest, the pharmacogenomics profile of the patients correlate with molecular response. Second generation tyrosine kinase inhibitors are currently evaluated. Discontinuation of the treatment has been successfully proposed to patients who achieved deep sustained molecular response.