Retrospective Evaluation Of Our Patients Diagnosed Chronic Myeloid Leukemia

Öz

Objective: Chronic myeloid leukemia(CML) is a myeloproliferative neoplasm, characterized by the unrestrained expansion of pluripotent bone marrow stem cells and accounts for %15 of newly diagnosed cases of leukemia in adults. Tyrosine kinase inhibitors (TKI) have become the main treatment of CML. Effective treatment for resistant cases has been achieved through the use of new-generation TKIs. In our study, we plan to offer contribution to the literature by examining the data of diagnosed CML patients retrospectively.

Material and Method: We retrospectively evaluated 88 CML patients, who demographic features, TKIs toxicity profiles and TKIs treatment responses,overal survival of the CML patients in Dokuz Eylül University Department of Hematology between 2003 and 2014

Results: We found that 36 of the patients were women and 53 of the patients were men and median age was 52. Response to treatment with imatinib was evaluated in terms of hematological, cytogenetic and molecular response based on ELN guidelines. On this analysis, 80%of patients treated TKIs had Complete Hematologic Response(CHR) at the 3. month, 75%of patient treated TKIs had Complete Cytogenetic Response (CCR) at the12 month and 75% of patient treated TKIs had Major Molecular Response (MMR) at the 18. month. The optimal response to imatinib was determined in 66% of patients. However, optimal response rate was 33% with the second generation of TKIs. The average follow-up period was 5.5 years for all patients with CML. All of the patients survival (OS) was 83%, Disease Free Survivor (DFS) was 100 months and 5 year overall survival rates of 92%.

Conclusion: As a result, CML patients with molecular monitoring should be done in accordance with all guidelines. Treatment changes must be made at the appropriate time and by considering the patient's comorbid conditions. Thus, long-term survival and disease-free survival can be achieved. However, care must be taken for cytogenetic and molecular monitoring to archieve a good patient follow-up.

Anahtar Kelimeler

• Chronic Myeloid Leukemia,Tyrosine Kinase Inhibitor,Treatment respons

Kronik Myeloid Lösemi Tanılı Hastalarımızın Retrospektif Değerlendirilmesi

Öz

Amaç: Kronik Miyeloid Lösemi (KML) pluripotent kök hücrelerin anormal çoğalması ile oluşan miyeloproliferatif bir hastalıktır ve erişkin lösemilerinin %15’ini oluşturur. Tirozin kinaz inhibitörleri (TKİ) KML’nin ana tedavisi haline gelmiştir. Yeni kuşak TKİ’lerinin kullanımı ile dirençli vakalarda etkin tedavi sağlanmıştır. Çalışmamızda KML tanılı hastaların retrospektif olarak verilerini inceleyerek literatüre katkı amaçlı sunmayı planladık.

Gereç ve yöntem: Çalışmamıza 2003 –2014 tarihleri arasında KML tanısı ile tedavi edilen 88 hastanın, demografik özelikleri, birinci ve ikinci sıra TKİ alan hastaların tedavi yanıtları,TKİ yan etkileri, tüm sağkalım (OS) durumları retrospektif olarak incelendi.

Bulgular: Olguların 36'sı kadın, 52'si erkek olup medyan yaş 52 idi. TKİ ile hematolojik, sitogenetik ve moleküler yanıtlar European Leukemia Net 2013 kılavuzuna göre değerlendirildi. Hastaların (n=88) TKİ’ne tedavi yanıtları 3. ay Tam Hematolojik Yanıt (THY) %80, 12. ay Tam Sitogenetik Yanıt(TSY) %75, 18. Ay Major Molekuler Yanıt (MMY) %75 olarak gözlendi. Buna göre İmatinib alan hastaların %66’sının optimal yanıtta oldukları saptandı. 2. Kuşak TKİ ile optimal yanıtta olan hasta yüzdesi %33 idi. Tüm KML hastalarında ortalama izlem süresi 5,5 yıldır. Olguların tüm sağkalım oranı (OS) % 83’tür. Hastalıksız sağ kalım süresi 100 ay (8,3 yıl), 5 yıllık tüm sağkalım oranı ise % 92 bulunmuştur.

Tartışma ve sonuç: Sonuç olarak KML hastalarında kılavuzlara uygun şekilde moleküler izlem yapılmalıdır. Tedavi değişikliği, zamanında ve hastanın komorbid durumlarını da gözeterek olmalıdır. Böylece uzun dönem sağkalım ve hastalıksız sağkalım elde edilebilir. Ancak iyi bir hasta izlemi için sitogenetik ve moleküler izleme özen gösterilmelidir.

Anahtar Kelimeler

• Kronik Myeloid Lösemi,Tirozin Kinaz İnhibitörü,Tedavi Yanıtları

Kaynakça

1. Referans1 Melo JV, Hughes TP Apperley JF. Chronic Myeloid Leukemi. In ASH Education Program Book 2003:132-152.
2. Referans2 Jemal A, Siegel R,Xu J,et al.Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300.
3. Referans3 Groffeu J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G. Philadelphia chrosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 1984;36:93-99.
4. Referans4 Rowley JD. Letter: a new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973;243:290-293.
5. Referans5 Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2014 update on diagnosis, monitoring and management. In ASH Education Program Book 2014;89:547-556.
6. Referans6 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: developed for the American Society of Hematology. Blood 1999;94:1517-1536.
7. Referans7 O Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine fo newly diagnosed chronic -phase chronic myeloid leukemia. N Engl J Med 2003;348:994-1004.
8. Referans8 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;349:1423-1432.

9. Referans9 Garcia-Gutierreinz JV,Herrera Pabalo LL,et al.İmpact of second-generation tyrosine kinase inhibitors as second line treatment for patients with chronic myeloid leukemia.Blood 2011;118:632.
10. Referans10 Cortes JE, Kim DW, Pinilla-Ibarz J, et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med 2013;369:1783-1796.
11. Referans11 Eskazan AE, Ayer M, Kantarcioglu B, Arica et al. First line treatment of chronic phase chronic myeloid leukaemia patients with the generic formulations of imatinib mesylate. Br J Haematol 2014;167:139-41.
12. Referans12 Kırkızlar O, Demir AM. Kronik Myeloid Lösemi: Patogenez, Klinik Özellikler, Tanı. Türkiye Klinikleri J Hem Onc-Special Topics 2015;5:1-6.
13. Referans13 Deininger M, O Brien SG, Guilhot F. et al. Internatıonal randomized study of ınterferon vs. STI571 (IRIS) 8 year follow up:sustained survival and low risk for progression of events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib.Blood 2009;114:3376-3381.
14. Referans14 Baccarani M, Deininger MW, Rosti G, et al. European Leukemia Net recommendations for the management of chronic myeloid leukemia. Blood 2013;122:872-884.
15. Referans15 Giuseppe Saglio, Dong-Wook Kim, Surapol Issaragrisil et al. Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia N Engl J Med 2010;362:2251-2259.
16. Referans16 Hochhaus A, Baccarani M, Deininger M, et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia 2008;22:1200-1206.
17. Referans17 Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260-2270.
18. Referans18 Jabbour E, Kantarjian HM, Saglio G, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia:3 year follow-up from a randomized phase 3 trial. (DASİSİON). Blood 2014;123:494-500. Referans19 Sahin F, Saydam G, Cömert M. et al. Turkish Chronic Myeloid Leukemia Study: Retrospective Sectional Analysis of CML Patients. Turk J Hematol 2013;30:351-358.
19. Referans20 Jain P,Kantarjian H, Alattar ML, et al. Long term molecular and cytogentic response and survival outcomes with imatinib 400 mg, imatinib 800,dasatinib and nilotinib in patients with chronic phase chronic myeloid leukemia: retrospective analysis of patient data from five clinical trials. Lancet Haematol 2015;2:118-12.
20. Referans21. Lipton JH, Chuah C, Guerci-Bresler A, et al. Epic: a phase 3 trial of ponatinib compared with imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase(CP-CML). Blood 2014;124:519.
21. Referans22. Philip A, Thompson MBBS, Hagop M, et al. Diagnosis and treatment of Chronic Myeloid Leukemia in 2015. Mayo Clinic 2015;90:1440-1454.
22. Referans23. Barret AJ and Ito S. The role of stem cell transplantation for chronic myelogenous leukemia in the 21st century. Blood 2015;125:3230-3235.
23. Referans24. Gratwohl A. The EBMT risk score. Bone Marrow Transplant 2012;47:749-756.
24. Referans25. Saussele S, Lauseker M, Gratwohl A et al. German CML Study Group. Allogeneic hematopoietic stem cell transplantation (allo SCT) for chronic myeloid leukemia in the imatinib area:evalution of its impact within subgroup of the randomized German CML Study IV. Blood 2010;115:1880-1885.