OUR EXPERIENCE IN TREATMENT OF CHRONIC MYELOID LEUKEMIA WITH IMATINIB MESYLATE
DOI:
https://doi.org/10.6016/ZdravVestn.2282Keywords:
chronic myeloid leukemia, tyrosine kinase, imatinib mesylate, Glivec®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.
Downloads
References
Kalidas M, Kantarjian HM, Talpaz M. Chronic myelogenous leukemia. JAMA 2001; 286: 895–8.
Melo JV. The molecular biology of chronic myeloid leukemia. Leukemia 1996; 10: 751–6.
Faderl S, Talpaz M, Estrov Z, Kantarjian HM. Chronic myelogenous leukemia: biology and therapy. Ann Intern Med 1999; 131: 207–19.
Schtivelman E, Lifshitz B, Gale RP, Canaani E. Fused transcript of ABL and BCR genes in chronic myelogenous leukaemia. Nature 1985; 315: 550–4.
Hochhaus A. Molecular response and resistance to imatinib (Glivec®). Hematology J 2003; 4: 15–20.
Silver RT, Woolf SH, Hehlmann R et al. An evidence based analysis of the effect of busulfan, hydroxyurea, interferon and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia. Blood 1999; 94: 1517–36.
O’Dwyer ME, Druker BJ. Chronic myelogenous leukaemia – new therapeutic principles. J Int Med 2001; 250: 3–9.
Hughes TP, Morgan GJ, Martiat P, Oldman JM. Detection of residual leukemia after bone marrow transplant for chronic myeloid leukemia. Blood 1991; 77: 874–8.
Hehlman R, Heimpel H, Hasford J et al. Randomized comparison of interferon alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. Blood 1994; 84: 4064–77.
Kantarjian HM, Smith TL, O’Brian S et al. Prolonged survival following achievement of cytogenetic response with alpha interferon therapy in chronic myelogenous leukemia. Ann Intern Med 1995; 122: 254–61.
Druker BJ, Lydon NB. Lessons learned from the development of an Abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest 2000; 105: 3–7.
Talpaz M, Silver RT, Druker B et al. A phase II study of STI 571 in adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in accelerated phase. Blood 2000; 96: 469a–9a.
Druker BJ, Tamura S, Buchdunger E et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 1996; 2: 561–6.
Schindler T, Bornmann W, Pellicina P et al. Structural mechanism for STI571 inhibition of abelson tyrosine kinase. Science 2000; 289: 1938–42.
Peggs K, Mackinnon S. Imatinib mesylate – the new gold standard for treatment of chronic myeloid leukemia. N Engl J Med 2003; 348: 1048–50.
Druker BJ, Sawyers CL, Kantarjian H et al. Activity of a specific inhibitor of the Bcr-Abl tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001; 344: 1038–42.
O’Brien SG, Guilhot F, Larson RA et al. Imatinib compared with interferon and low dose cytarabine for newly diagnosed chronic phase chronic myeloid leukemia. N Engl J Med 2003; 348: 994–1004.
Branford S, Walsh S, Rudzki Z et al. Imatinib produces significantly superior molecular responses compared to interferon plus low dose Ara C in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood 2002; 100: 96a–6a.
Goldman J. Implications of imatinib mesylate for hematopoietic stem cell transplantation. Semin Hematol 2001; 38: 28–34.
Goldman J. Novel treatment approaches. Haematol J 2003; 4: 21–4.
Fischer T. Beyond CML – new horizonts for imatinib. 8th EHA Congress, Lyon, June 12–15, 2003. Lyon: European Haematologic Association, 2003.
Downloads
Issue
Section
License
The Author transfers to the Publisher (Slovenian Medical Association) all economic copyrights following form Article 22 of the Slovene Copyright and Related Rights Act (ZASP), including the right of reproduction, the right of distribution, the rental right, the right of public performance, the right of public transmission, the right of public communication by means of phonograms and videograms, the right of public presentation, the right of broadcasting, the right of rebroadcasting, the right of secondary broadcasting, the right of communication to the public, the right of transformation, the right of audiovisual adaptation and all other rights of the author according to ZASP.
The aforementioned rights are transferred non-exclusively, for an unlimited number of editions, for the term of the statutory
The Author can make use of his work himself or transfer subjective rights to others only after 3 months from date of first publishing in the journal Zdravniški vestnik/Slovenian Medical Journal.
The Publisher (Slovenian Medical Association) has the right to transfer the rights of acquired parties without explicit consent of the Author.
The Author consents that the Article be published under the Creative Commons BY-NC 4.0 (attribution-non-commercial) or comparable licence.
