ISPARTA’DAKİ KRONİK MYELOİD LÖSEMİ HASTALARININ GERÇEK YAŞAM VERİLERİ

Abstract

Amaç Kronik myeloid lösemi (KML), 100.000 yetişkinde 1-2 vaka insidansı olan myeloproliferatif bir neoplazmdır. KML' nin patogenezinin merkezi, kromozom 9 üzerindeki Abelson murin lösemi (ABL1) geni ile, kromozom 22 üzerindeki kırılma noktası bölgesi (BCR) geninin füzyonudur. KML tedavisi, tirozin kinaz inhibitörlerinin (TKİ) bulunması ile değişmiştir. Bu hedeflenmiş yaklaşım, KML' nin doğal seyrini değiştirmiş ve 10 yıllık sağ kalım oranını yaklaşık %80-90’lara çıkarmıştır. TKİ ile tedavi altında olan “gerçek hayat” KML hastalarımızda etkin tedavi yönetiminin yapılıp yapılmadığı, tedavi yanıt oranları ve sağ kalım verilerinin güncel literatür ile benzer olup olmadığının araştırılması amaçlanmıştır. Gereç ve Yöntem Süleyman Demirel Üniversitesi Tıp Fakültesi Hematoloji Bilim Dalı’nda 2000-2018 yılları arasında KML tanısı alan 58 KML hastası çalışmaya alınmıştır. Bu çalışmada hastaların klinik, laboratuvar ve demografik özellikleri, tedavi seçenekleri, yan etkileri ve yanıtları değerlendirildi. Sokal, Hasford ve Eutos risk puanlama sistemi ve Dünya Sağlık Örgütü kriterleri ile risk değerlendirmesi ve evrelemesi uygulandı. European Leukemia Network’ün kriterlerine göre hematolojik, sitogenetik ve moleküler yanıtı belirledik. Bulgular Çalışmamızda literatürle benzer yaş ortalaması, erkek/ kadın oranı saptandı. Çalışmamızda yaş dağılımının (p=0,001) Charlson komorbidite İndeksi’ nin (p=0,005) ve Charlson komorbidite-yaş İndeksi’ nin (p=0,000) genel sağkalıma istatistiksel olarak anlamlı etki ettiği görülmüştür. Çalışmamızda yaş dağılımının (p = 0.029), Charlson komorbidite yaş İndeksi (p = 0,001) ve 12. ayda Major Moleküler Yanıt (MMY) alınmasının (p = 0,028) hastalıksız sağkalıma istatistiksel olarak anlamlı etki ettiği görülmüştür. Çalışmamızda sadece 12. Ayda MMY (p=0,006) progresyonsuz sağkalıma istatistiksel olarak anlamlı etki ettiği görülmüştür. Hastalarda retiküler lif derecesinin genel sağkalım, hastalıksız sağkalım ve progresyonsuz sağkalıma önemli ölçüde etki etmediği saptanmıştır. Sonuç Bu sonuçlar, KML'nin genellikle mevcut tedavilerle iyi yönetildiğini ve ölümlerin diğer tıbbi problemler nedeniyle daha sık meydana geldiğini göstermektedir. KML’de, Charlson indekslerinin genel sağ kalım ve hastalıksız sağ kalımla anlamlı derecede ilişkili olduğu gösterilmiştir.

Keywords

• Charlson komorbidite indeksi
• Charlson komorbidite-yaş indeksi
• Gerçek yaşam verileri
• Kronik Myeloid Lösemi
• Prognoz

REAL LIFE DATA OF CHRONIC MYELOID LEUKEMIA PATIENTS IN ISPARTA

Abstract

Objective Chronic myeloid leukemia is a myeloproliferative neoplasm with an incidence of 1–2 cases per 100 000 adults. Central to the pathogenesis of CML, is the fusion of the Abelson murine leukemia (ABL1) gene on chromosome 9 with the breakpoint cluster region (BCR) gene on chromosome 22. The therapeutic landscape changed dramatically with the development of the tyrosine kinase inhibitors (TKIs). This “targeted” approach altered the natural history of CML, improving the 10-year survival rate to 80-90%. This study aims to investigate the effective management of TKI treatment and overall survival in “real-life” CML patients and to discuss the results with current literature. Material and Method Fifty-eight patients who were diagnosed as CML between 2000 and 2018 in Suleyman Demirel University Hematology Department were evaluated. Patients’ clinical and laboratory characteristics, clinical and demographical features, treatment options, side effects and responses were evaluated in this study. Risk assessment and staging applied with World Health Organization criteria and Sokal Hasford and Eutos risk scoring system. We determined hematological, cytogenetic and molecular response according to European Leukemia Network criteria. Results The average age, male / female ratio and survival rates were found similar to those in literature. The age distribution (p = 0,001) and Charlson comorbidity index (p = 0.005) and Charlson comorbidity-age index (p = 0,000) had a statistically significant effect on overall survival. Age distribution (p = 0,029), Charlson comorbidity age index (p = 0,001) and major molecular response at 12 months (p = 0,028) were found to have a significant effect on disease-free survival. Major molecular response at 12 months (p = 0,006) also had a statistically significant effect on progression-free survival. Reticular fiber grade did not significantly affect overall survival, disease-free survival and progressionfree survival of patients. Conclusion These results suggest that CML is generally well managed with existing treatment options and that death occur more frequently due to other medical problems. In CML, Charlson indices have been shown to be significantly associated with overall survival and disease-free survival.

Keywords

• Charlson comorbidity index
• Charlson comorbidity-age index
• Chronic Myeloid Leukemia
• Real life data
• Prognosis

References

1. 1. Minciacchi VR, Kumar R, Krause DS. Chronic Myeloid Leukemia: A Model Disease of the Past, Present and Future. Cells. 2021 Jan 10;10(1):117.
2. 2. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. American journal of hematology. 2018;93(3):442-59.
3. 3. Braithwaite D, Demb J, Henderson L. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, GA: American Cancer Society. 2016.
4. 4. Deininger M, O'Brien SG, Guilhot F, Goldman JM, Hochhaus A, Hughes TP, et al. International Randomized Study of Interferon vs STI571 (IRIS) 8-Year Follow up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. Blood. 2009 Nov 20;114(22):1126.
5. 5. Lin Q, Mao L, Shao L, Zhu L, Han Q, Zhu H, et al. Global, Regional, and National Burden of Chronic Myeloid Leukemia, 1990- 2017: A Systematic Analysis for the Global Burden of Disease Study 2017. Front Oncol. 2020 Dec 15;10:580759.
6. 6. Hemmati, Philipp. Chronische Leukämien: Diagnostik und Therapie in der klinischen Praxis. CME. 2018;15:9-22. Doi: 10.1007/s11298-018-6512-9.
7. 7. Huang XL, Cortes J, Kantarjian H. Estimations of the increasing prevalence and plateau prevalence of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. Cancer. 2012 Jun 15;118(12):3123-7. doi: 10.1002/cncr.26679.
8. 8. O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. New England Journal of Medicine. 2003;348(11):994-1004.

9. 9. Radich JP, Kopecky KJ, Appelbaum FR, Kamel-Reid S, Stock W, Malnassy G, et al. A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic-phase chronic myeloid leukemia. Blood. 2012;120(19):3898-905.
10. 10. Sahin F, Saydam G, Cömert M, Uz B, Yavuz AS, Turan E, et al. Turkish Chronic Myeloid Leukemia Study: Retrospective Sectional Analysis of CML Patients. Turk J Haematol. 2013 Dec;30(4):351-8.
11. 11. Eskazan AE, Soysal T. Generic imatinib in the treatment of chronic myeloid leukemia: Cerrahpaşa experience. J Oncol Pharm Pract. 2016 Apr;22(2):382-4.
12. 12. Saglio G, Kim D-W, Issaragrisil S, Le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. New England Journal of Medicine. 2010;362(24):2251-9.
13. 13. Sacha T. Imatinib in chronic myeloid leukemia: an overview. Mediterranean journal of hematology and infectious diseases. 2014;6(1).
14. 14. Saußele S, Krauß M-P, Hehlmann R, Lauseker M, Proetel U, Kalmanti L, et al. Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML study IV. Blood. 2015;126(1):42-9.
15. 15. Jabbour E, Kantarjian H, O'Brien S, Shan J, Quintas-Cardama A, Faderl S, et al. The achievement of an early complete cytogenetic response is a major determinant for outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors. Blood. 2011;118(17):4541-6.
16. 16. Kuntegowdanahalli LC, Kanakasetty GB, Thanky AH, Dasappa L, Jacob LA, Mallekavu SB, et al. Prognostic and predictive implications of Sokal, Euro and EUTOS scores in chronic myeloid leukaemia in the imatinib era—experience from a tertiary oncology centre in Southern India. Ecancermedicalscience. 2016 Oct 6;10:679. doi: 10.3332/ecancer.2016.679.
17. 17. Zhang XS, Gale RP, Huang XJ, Jiang Q. Is the Sokal or EUTOS long-term survival (ELTS) score a better predictor of responses and outcomes in persons with chronic myeloid leukemia receiving tyrosine-kinase inhibitors? Leukemia. 2022 Feb;36(2):482-491.
18. 18. Kantarjian HM, Bueso-Ramos CE, Talpaz M, O'Brien S, Giles F, Rios MB, et al. The degree of bone marrow fibrosis in chronic myelogenous leukemia is not a prognostic factor with imatinib mesylate therapy. Leuk Lymphoma. 2005 Jul;46(7):993-7. doi: 10.1080/10428190500097581.