KRONİK FAZ KRONİK MYELOİD LÖSEMİDE HEDEFE YÖNELİK TEDAVİNİN GERÇEK HAYATTA UZUN DÖNEM İZLEM SONUÇLARI: TEK MERKEZ DENEYİMİ

Öz

Amaç: Kronik myeloid lösemi (KML), myeloid seri hücrelerinde aşırı ve kontrolsüz çoğalmayla karakterize olan bir hematopoetik kök hücre hastalığıdır. Tirozin kinaz inhibitörleri (TKİ) ile KML tedavisinde başarı yüksek oranda artmıştır. Bu hastaların uzun dönem takibinde hedefe yönelik tedavinin yan etki yönetimi, yanıt kaybı ve ilaca direnç mekanizmalarının yakından izlemi klinik pratikte önem kazanmıştır. Bu çalışmada da ünitemizde tedavi alan ve takip altında olan kronik faz KML hastalarının klinik seyirlerinin geriye dönük değerlendirilmesi amaçlanmıştır.

Gereç ve Yöntem: Haziran 2001 - Aralık 2016 tarihleri arasında tanı almış, TKİ ile tedavi edilen 72 kronik faz KML olgusunun sonuçları geriye dönük olarak değerlendirilmiştir.

Bulgular: Çalışmaya tanı anı medyan yaşı 40 (16-66) olan 36 (%50)’sı kadın ve 36 (%50)’sı erkek toplam 72 olgu dahil edildi. Tanı sonrası takip süresi medyan 88 (20-207) ay, toplam sağ kalım ise medyan 92,5 (21-207) ay idi. Halen takipte olan 68 olgunun 65 (%95,6)’inin majör moleküler yanıt ile ve 3 (%4,4) olgunun ise tam sitogenetik yanıt ile takip edildiği gözlendi.

Sonuç: Kronik faz KML olgularında prognoz, son 20 yılda TKİ’lerinin klinik pratiğe girmesiyle dramatik bir şekilde iyileşmiştir ve yaşam beklentisi genel sağlıklı popülasyona yaklaşmıştır. KML hastalarının günlük pratik izleminde, kılavuzlarda ki önerilere azami düzeyde uyulmalıdır.

Anahtar Kelimeler

• myeloid lösemi,kronik,kronik faz

LONG TERM TREATMENT RESULTS OF TARGETED THERAPY IN CHRONIC PHASE CHRONIC MYELOID LEUKEMIA: SINGLE CENTER EXPERIENCE

Öz

Purpose: Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease characterized by excessive and uncontrolled proliferation in myeloid cells. Treatment success in CML has been significantly increased with tyrosine kinase inhibitors (TKIs). In the long-term follow-up of CML patients, side-effect management of targeted therapy, loss of response and close monitoring of drug resistance mechanisms have gained importance in clinical practice. The aim of this study was to evaluate the clinical course of chronic phase CML patients who were treated and followed up in our center, retrospectively.

Material and Method: The results of 72 chronic phase CML patients treated with TKIs between June 2001 and December 2016 were evaluated retrospectively.

Results: Seventy-two patients (36 (50%) female and 36 (50%) male) with a median age of 40 years (16-66) were included in the study. The median follow-up period was 88 (20-207) months and the median overall survival was 92.5 (21-207) months. Sixty-five (95.6%) of 68 patients who were still under follow-up had major molecular response and 3 (4.4%) had complete cytogenetic response.

Conclusion: The prognosis of chronic phase CML patients has improved dramatically in the last 20 years with the introduction of TKIs into clinical practice, and life expectancy has approached the general healthy population. In the daily practical follow-up of CML patients, the recommendations in the guidelines should be strictly followed.

Anahtar Kelimeler

• myeloid leukemia,chronic,chronic phase

Kaynakça

1. Referans1. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127(20): 2391-405.
2. Referans2. Tefferi A. Chronic myeloid disorders: Classification and treatment overview. Semin Hematol 2001; 38: 1-4.
3. Referans3. Hoglund M, Sandin F, Simonsson B. Epidemiology of chronic myeloid leukaemia: an update. Ann Hematol 2015; 94: 241-7.
4. Referans4. Hochhaus A, Saussele S, Rosti G, et al. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017; 28: 41–51.
5. Referans5. Goldman JM. Chronic myeloid leukemia: a historical perspective. Semin Hematol 2010; 47(4): 302-11.
6. Referans6. Pavlu J, Szydlo RM, Goldman JM, Apperley JF. Three decades of transplantation for chronic myeloid leukemia: what have we learned? Blood 2011; 117(3): 755-63.
7. Referans7. Kantarjian HM, O’Brien S, Cortes J, et al. Imatinib mesylate therapy improves survival in patients with newly diagnosed philadelphia chromosome-positive chronic myelogenous leukemia in the chronic phase: comparison with historic data. Cancer 2003; 98(12): 2636-42.
8. Referans8. Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naive Chronic Myeloid Leukemia Patients Trial. J Clin Oncol 2016; 34(20): 2333-40.

9. Referans9. Hochhaus A, Saglio G, Hughes TP, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia 2016; 30(5): 1044-54.
10. Referans10. Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. J Clin Oncol 2018; 36(3): 231-7.
11. Referans11. Patel AB, Wilds BW, Deininger MW. Treating the chronic-phase chronic myeloid leukemia patient: which TKI, when to switch and when to stop? Expert Rev Hematol 2017; 10(7): 659-74.
12. Referans12. Network. NCCN clinical practice guidelines in oncology: chronic myelogenous leukemia version 2. NCCN; 2018. p. 2017.
13. Referans13. Baccarani M, Castagnetti F, Gugliotta G, Rosti G. A review of the European LeukemiaNet recommendations for the management of CML. Ann Hematol 2015; 94: 141-7.
14. Referans14. Steegmann JL, Baccarani M, Breccia M, et al. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia 2016; 30(8): 1648-71.
15. Referans15. Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med 1999; 341(3): 164-72.
16. Referans16. Savage DG, Szydlo RM, Goldman JM. Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia seen at a referral centre over a 16-year period. Br J Haematol 1997; 96(1): 111-6.
17. Referans17. Druker BJ. Translation of the Philadelphia chromosome into the rapy for CML. Blood 2008; 112(13): 4808-17.
18. Referans18. Cortes J, Kantarjian H. How I treat newly diagnosed chronic phase CML. Blood 2012; 120(7): 1390-7.
19. Referans19. 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(11): 994-1004.
20. Referans20. Kantarjian HM, Cortes JE, O'Brien S, et al. Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses. Blood 2003; 101(1): 97-100.
21. Referans21. Hughes TP, Kaeda J, Branford S, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med 2003; 349(15): 1423-32.
22. Referans22. Hehlmann R, Müller MC, Lauseker M, et al. Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV. J Clin Oncol 2014; 32(5): 415-23.
23. Referans23. Lee SE, Choi SY, Kim SH, et al. Comparative analyses of nilotinib versus high-dose imatinib versus sustained standard-dose imatinib in patients with chronic phase chronic myeloid leukemia following suboptimal molecular response to first-line imatinib. Leuk Res 2018; 70: 100-105.
24. Referans24. Jabbour E, Kantarjian H, O'Brien S, et al. Sudden blastic transformation in patients with chronic myeloid leukemia treated with imatinib mesylate. Blood 2006; 107(2): 480-2.
25. Referans25. Hochhaus A, Larson RA, Guilhot F, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med 2017; 376(10): 917–27.
26. Referans26. Brave M, Goodman V, Kaminskas E, et al. Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. Clin Cancer Res 2008; 14(2): 352-59.
27. Referans27. Giles FJ, le Coutre PD, Pinilla-Ibarz J, et al. Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study. Leukemia 2013; 27(1): 107-12.