OUR EXPERIENCE IN TREATMENT OF CHRONIC MYELOID LEUKEMIA WITH IMATINIB MESYLATE
Abstract
Background. Chronic myeloid leukemia is a clonal disease of hematopoietic stem cell which progresses through three phases. During progression, leukemic cells become therapy resistant and patients die of acute leukemia. Disease specific is the presence of Philadelphia chromosome, the result of reciprocal translocation between the chromosomes 9 and 22. The molecular consequence of this translocation is the BCR-ABL fusion protein with tyrosine kinase activity which induces malignant transformation to leukemia. Imatinib mesylate (Glivec®) is the first sintetised drug with tyrosine kinase blocking activity.
Patients and results. We represent 9 patients with chronic myeloid leukemia who were treated with imatinib from 2000 till now. Three of them were in chronic phase, two in accelerated phase and four in blast crysis. The average age was 59 years while the average time from the disease onset till imatinib treatment was 57.77 months. All of them were previous treated with interferon and/or hydroxyurea. The initial dose of imatinib was 600 mg. The patients were treated from the period ranging from 2.5 till 28 months. Three of them in chronic phase showed complete cytogenetic, two in blastic phase partial cytogenetic remission and all of them showed complete hematologic remission. Four patients in blastic crysis died during the therapy. Seven of them showed mild side effects.
Conclusions. Imatinib binds to the ATP binding site on BCR-ABL fusion protein and inhibits the phosphorilation of substrate and subsequent by inhibits malignant cell transformation. The drug is active in all three phases of the disease. In addition, it inhibits also platelet derived growth factor and c-KIT. However it is inactive against other tyrosine kinases. Imatinib is now treatment of choice in all patients in chronic phase of the disease and is in clinical testing in patients in transplantation programme. It is well tolerated although in most cases mild dose dependent side effects can be seen and drug resistance can develope.
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