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
Project Number
Yok
References
- 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. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. American journal of hematology. 2018;93(3):442-59.
- 3. Braithwaite D, Demb J, Henderson L. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, GA: American Cancer Society. 2016.
- 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. 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. Hemmati, Philipp. Chronische Leukämien: Diagnostik und Therapie in der klinischen Praxis. CME. 2018;15:9-22. Doi: 10.1007/s11298-018-6512-9.
- 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. 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. 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. 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. 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. 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. Sacha T. Imatinib in chronic myeloid leukemia: an overview. Mediterranean journal of hematology and infectious diseases. 2014;6(1).
- 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. 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. 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. 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. 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.
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
Supporting Institution
Yok
Project Number
Yok
Thanks
YOk
References
- 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. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. American journal of hematology. 2018;93(3):442-59.
- 3. Braithwaite D, Demb J, Henderson L. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, GA: American Cancer Society. 2016.
- 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. 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. Hemmati, Philipp. Chronische Leukämien: Diagnostik und Therapie in der klinischen Praxis. CME. 2018;15:9-22. Doi: 10.1007/s11298-018-6512-9.
- 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. 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. 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. 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. 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. 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. Sacha T. Imatinib in chronic myeloid leukemia: an overview. Mediterranean journal of hematology and infectious diseases. 2014;6(1).
- 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. 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. 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. 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. 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.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Araştırma Makaleleri |
| Authors | |
| Project Number | Yok |
| Publication Date | December 30, 2023 |
| Submission Date | March 20, 2023 |
| Acceptance Date | November 14, 2023 |
| Published in Issue | Year 2023 Volume: 30 Issue: 4 |
Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi/Medical Journal of Süleyman Demirel University is licensed under Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International.