Gleevek therapy resistance in patients with chronic myeloid leukemia in the acceleration phase.

Gleevek therapy resistance in patients with chronic myeloid leukemia in the acceleration phase. S.S.Kruglov, A.G.Turkina, N.D.Khoroshko, E.M.Abakumov, G.A.Druzhkova, A.V.Zakharova, E.V.Domracheva, T.I.Kolosheinova, L.Yu.Kolosova, L.G.Kovalyova, L.V.Dyachenko, E.Yu.Chelysheva, L.A.Chernova, S.S.Loriya. Hematology Research Center, Moscow; Federal Research and Clinical Center of Pediatric Hematology, Oncology, and Immunology, Moscow. The aim of this study was to evaluate the incidence of additional chromosome aberrations and their relationship with gleevek resistance. We analyzed clinical and laboratory findings in 116 Ph+ and BCR-ABL+ patients with chronic myeloid leukemia (CML) in the acceleration phase. All patients received therapy with BCR-ABL tyrosine kinase inhibitor Gleevek(r) ("Novartis Pharma AG", Switzerland) in a daily dose of 600 mg. Complete recovery of Ph-negative hemopoiesis was attained in 36.2% patients and was associated with 93% 4-year survival vs 30% in patients without cytogenetic response. The notions of hematological and cytogenetic resistance are formulated and the terms for its diagnosis are determined. Different approaches to drug resistance control are demonstrated (increase of gleevek dose, chemotherapy, combined therapy). The significance of additional chromosome aberrations, detected in Ph-positive and Ph-negative cells by the beginning and during gleevek therapy, is evaluated. Unfavorable prognostic clinical hematological signs, significantly related to treatment resistance and low survival, are detected.