DASATINIB IN CHRONIC MYELOID LEUKEMIA

Abstract

BACKGROUND The BCR-ABL tyrosine kinase inhibitor imatinib is effective in Philadelphia chromosomepositive CML (chronic myeloid leukemia), but relaps occurs, mainly as a reults of the outgrowth of leukemic subclones with imatinib resistant BCR-ABL mutation.Some patientswith various phases of CML note tolerate imatinib. Dasatinib is an orally available ABLkinase inhibitor that differs from imatinib in that it can bind to both the active andinactive conformation of the ABL kinase domain.The oral inhibitor tirozin kinazedasatinib was approved in 2006 for use in patients with CML who are unable to tolerate orhave not responder to other treatments.Patients We treated 2 patients in chronic phase CML who dident tolerate imatinib (400 mg per day)and one patient in accelerated phase CML (imatinib 800 mg per day) withdasatinib.Dasatinib was administered orally (50 to 140 mg per day) once or twice daily. Hematologic and cytogenetic responses were seen in 2 patients. Myelosuppression was commonbut not dose – limiting. One patients in chronic phase CML didnt tolerate also dasatinib.He had rush, nausea and vomiting. CONCLUSIONS Dasatinib induces hematologic and cytogenetic responses in patients with CML whocannot tolerate or are resistant to imatinib. Dasatinib has shown clinical benefit andtolerability in patients in all phases of CML