İmatinib tedavisi alan kronik myeloid lösemi hastalarında tedavi etkinliğinin ve prognozun değerlendirilmesi

Amaç: Kronik myeloid lösemi (KML), immatür hematopoietik kök hücrelerinin neoplastik transformasyonu sonucuoluşan klonalmyeloproliferatif bir hastalıktır. Spesifik BCR-ABL protein tirozin kinaz inhibitörü (TKİ) imatinib mesilatklinik uygulamaya girdikten sonra KML tedavisinde yeni bir dönem başlamıştır. Bugün KML tedavisinde imatinibmesilat ilk tercih edilen tedavi seçeneğidir ancak imatinib mesilat tedavisine yanıtsızlık ve intoleransgelişebilmektedir. Bu çalışmamızda TKİ tedavisi verilen KML hastalarında tedavi etkinliğinin ve prognozundeğerlendirilmesi amaçlandı.Yöntemler: Çalışmamızda Hacettepe Üniversitesi Tıp Fakültesi Erişkin Hastanesi Hematoloji Ünitesinde Kasım 1995ile Aralık 2009 tarihleri arasında takip edilen 16 yaşından büyük 54 KML hastası çalışmaya dahil edildi. Verilereretrospektif olarak hasta dosya kayıtlarından ulaşıldı. Hastaların TKİ başlandığı sıradaki hastalık evrelemesi DünyaSağlık Örgütü (WHO) kriterlerine göre yapıldı. Tanı anındaki risk profiliSokal risk skorlamasına göre değerlendirildi.Yanıt oranları (hematolojik ve sitogenetik), relaps oranı (hematolojik, sitogenetik ve moleküler relapstan herhangibirinin varlığı), relaps bağımsız sağkalım ve genel sağkalım değerlendirildi. Hastaların sağkalım eğrileri Kaplan Meieryöntemi ile değerlendirildi.Bulgular: Çalışmamızda hastaların %94,4’ ünde tam hematolojik yanıt (THY) ve %75,9’ unda tam sitogenetik yanıt(TSY) elde edildi. Çalışmamızda relaps oranı %31,5 olarak bulundu. Hastaların %40’ında imatinib tedavisisonlandırıldı. Bu hastaların %40’ında primerimatinib direnci, %46,6’ sında sekonder imatinib direnci ve %13,4’ ündeyan etki nedeniyle tedavi sonlandırıldı. 18 aylık ve 5 yıllık relaps bağımsız sağkalım sırasıyla %86,7 ve %56,2 idi.Genel sağkalım açısından değerlendirildiğinde, 3 ve 5 yıllık genel sağkalım oranı %93,7 olarak hesaplandı.Sonuç: imatinib tedavisinin tolere edilebilir etkin bir tedavi yöntemi olduğu ancak günümüzde daha yeni TKİ’ lerinklinik uygulamaya girmesiyle birlikte, TKİ’ leri veya kombinasyonlarını etkinlik ve tolerabilite açısından kıyaslayacakçalışmaların yapılmasıyla, KML tedavisinde en uygun tedavi seçeneğinin belirlenebileceği düşünüldü.

Evaluation of efficacy of treatment and prognosis in chronic myeloid leukemia patients treated with imatinib

Objective: Chronic myeloid leukemia (CML), is a clonal myeloproliferative disease due to neoplastic transformation of immature hematopoietic stem cells. The introduction of imatinib mesylate, specific BCR-ABL tyrosine kinase inhibitor (TKİ), opened a new era in treatment of CML. Currently, imatinib is considered as the first line treatment regime for CML however nonresponse or intolerance to imatinib therapy may develop. The aim of our study is to evaluate the prognosis and the efficacy of treatment in CML patients treated with TKİ. Methods: In the study; 16 years old and older 54 patients with CML who had been followed-up at Adult Hematology Department in the university hospital between November 1995 and December 2009, were analyzed retrospectively. The disease phases of patients when the TKİ was started were defined according to criteria proposed by World Health Organization (WHO). Risk profiles of patients at the time of diagnosis were determined by Sokal risk scoring system. Response rates (hematologic and cytogenetic), relapse rate (hematologic, cytogenetic or molecular relapse), relapse free survival and overall survival were evaluated. The survival curves were evaluated by Kaplan Meier method. Results: In our study, complete hematologic response(CHR) and complete cytogenetic response (CCR) rates were 94.4% and 75.9%, respectively. Relapse rate was 31.5%. Imatinib therapy was discontinued 40% of patients. Causes for imatinib discontinuation were primary imatinib resistance (40%), secondary imatinib resistance (46.6%) and side effects (13.4%). Estimated rate of relapse free survival was86.7% at 18 months and 56.2% at 5 years. Estimated three-year and five-year overall survival rates were 93.7%. Conclusion: It was concluded that imatinib mesylate is an effective and tolerable treatment choice but further studies that compares TKİ’ s or combinations in terms of efficacy and tolerabilitiy are required to decide the most appropriate treatment choice in CML treatment.

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Fialkow PJ, Jacobson RJ, Papayannopoulou T.Chronic myelocyticleukemia: clonalorigin in a stemcell common to the granulocyte, erythrocyte, platelet and monocyte/ macrophage. Am J Med, 1977. 63: 125–30.
Faderl S, Talpaz M, Estrov Z ve ark. The biology of chronicmyeloid leukemia. N Engl J Med, 1999. 341: p. 164-72.
Sawyers CL, Chronic myeloid leukemia. N Engl J Med, 1999; 340 : p. 1330-40.
Bennett J, Case of hypertrophy of the spleen liver, in which death took place from suppuration of the blood. Edinb. Med. Surg. J, 1845; 64: p. 413-23.
Nowell P, Hungerford D. "A minute chromosome in chronic granulocytic leukemia." Science 1960; 132: 1497.
Rowley JD. A new consistent chromosomalab normality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature, 1973; 243:290-3.
Goldman JM, Melo JV. Chronic myeloid leukemiaadvances in biology and new approaches to treatment. N.Engl J Med, 2003. 349:1451-64.
Deininger MW, Goldman JM ve Melo JV. The molecular biology of chronic myeloid leukemia. Blood, 2000; 96: p. 3343-56.
Tefferi A, Thiele J, Orazi A ve ark. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc internationalexpert panel. Blood, 2007; 110: 1092–7.
Cortes JE, Talpaz M, Beran M ve ark. Philadelphia chromosome-negative chronic myelogenous leukemia with rearrangement of the break point cluster region. Long-term follow-upresults. Cancer, 1995; 75: p. 464- 70.
Garcia-Manero G, Talpaz M ve Kantarjian HM. Current therapy of chronic myelogenous leukemia. Intern Med, 2002. 41: p. 254-64.
The Italian Cooperative Study Group on Chronic Myeloid Leukemia. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med, 1994; 330: p. 820-5.
Carolina P, Kantarjian HM, Cortes JE. Firstlinetherapy for chronic myeloid leukemia: past, present, and future. Am. J. Hematol, 2009; 84: 287–93.
de Lavallade H, Apperley JF, Khorashad JS ve ark. Imatinib for new lydiagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treatanalysis. J Clin Oncol. 2008; 26: 3358-63.
Yasuhito Nannya, Hiromitsu Yokota, Yumiko Sato ve ark. Molecular and cytogenetic response of chronic myelogenous leukemia treated with imatinib mesylate: one institutiona experience in Japan. Int J Hematol. 2008; 88: 159–64.
E Yanmin Zhao, Lizhen Liu, Yingjia Wang ve ark. Efficacyand prognosis of chronic myeloid leukemia treated with imatinib mesylate in a Chinese population. Int J Hematol. 2009; 89: 445–51.
Palandri F, Castagnetti F, Testoni Nve ark. Chronic myeloid leukemia in blast crisis treated with imatinib 600 mg: outcome of the patients alive after a 6-year followup. Haematologica. 2008, 93: 1792-6.
Lee JP, Birnstein E, Masiello D ve ark. Gender and ethnic differences in chronic myelogenous leukemia prognosis and treatment response: a single institution retrospective study. J Hematol Oncol. 2009; 2: 30.
Matsuo E, Miyazaki Y, Tsutsumi C ve ark. Imatinib provides durable molecular and cytogenetic responses in a practical setting for both newly diagnosed and previously treated chronic myelogenous leukemia: a study in nagasaki prefecture, Japan. Int J Hematol. 2007;85: 132-9.
Baccarani M, Saglio G, Goldman J ve ark. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European Leukemia Net. Blood. 2006 Sep 15; 108: 1809-20.