•  
  •  
 

Abstract

Introduction. The complete hematologic response is an integral part to achieve the complete cytogenetic response target and the major molecular response of imatinib mesylate therapy, although it does not determine the prognosis. The complete hematologic response in Indonesia is lower than in the world (74% vs. 95%). Sixty percent of chronic myeloid leukemia patients in Indonesia were administered hydroxyurea before imatinib mesylate. Chronic myeloid leukaemia (CML) patients in Indonesia are younger than in other countries. This study aimed to determine what prognostic factors which affect the complete hematological response of chronic phase CML patients who received imatinib mesylate in Indonesia. Methods. The study was done by retrospective cohort design using the medical records data of chronic myeloid leukemia patients who were treated at Teratai Clinic and hematology clinic RSCM and received imatinib mesylate therapy from January 2004-December 2011. Results. Most of the study subjects were male (61.5%), aged 26-40 years (47.4%), duration of diagnosis <12 months>(69.2%), duration of hydroxyurea therapy <6 months>(64.1%), hemoglobin concentration <12 g>/dl (69.2%), leukocyte count ≥50,000 (48.7%), platelet count 0 – <450,000 (42.3%), spleen size ≥10 cm (55.1%), low Sokal score (42.3%), and achieve a complete hematologic response within 3 months (57.7%). Duration of hydroxyurea therapy <6 months is prognostic factor higher CHR achievement. Conclusions. Clinical and laboratory characteristics CML patients in Indonesia are different than CML patients in the world. Duration of diagnosis until imatinib mesylate administration <12 months, duration of hydroxyurea administration <6 months, and hemoglobin concentration ≤12 g/dl were associated with the achievement of complete hematological response of chronic CML patients in Indonesia. Duration of hydroxyurea administration <6 months was identified as independent factor of achievement of complete hematological response of chronic CML patients in Indonesia.

References

1. Jiang Y, Xu P, Yao D, Chen X, Dai H. CD33, CD96 and death associated protein kinase (DAPK) expression are associated with the survival rate and/or response to the chemotherapy in the patients with acute myeloid leukemia (AML). Med Sci Monit Int Med J Exp Clin Res. 2017;23:1725–32. 2. Rao KV, Iannucci A, Jabbour E. Current and future clinical strategies in the management of chronic myeloid leukemia. Pharmacother J Hum Pharmacol Drug Ther. 2010;30(9P2):77S-101S. 3. Palandri F, Iacobucci I, Castagnetti F, Testoni N, Poerio A, Amabile M, et al. Front-line treatment of Philadelphia positive chronic myeloid leukemia with imatinib and interferon-α: 5-year outcome. Haematologica. 2008;93(5):770–4. 4. Deininger MWN, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood. 2000;96(10):3343–56. 5. Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia. N Engl J Med. 2006;355(23):2408–17. 6. Mughal A, Aslam HM, Khan AMH, Saleem S, Umah R, Saleem M. Bcr-Abl tyrosine kinase inhibitors- current status. Infect Agent Cancer. 2013;20;8:23. 7. 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;114(22):1126. 8. Cojbasić I, Macukanović-Golubović L. Prognostic factors associated with complete cytogenetic response in patients with chronic myelogenous leukemia on imatinib mesylate therapy. Srp Arh Celok Lek. 2010;138(5–6):305–8. 9. Kantarjian HM, Cortes JE, O’Brien S, Luthra R, Giles F, Verstovsek S, et al. Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-alpha. Blood. 2004;104(7):1979–88. 10. Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346(9):645–52. 11. Talpaz M, Silver RT, Druker BJ, Goldman JM, Gambacorti-Passerini C, Guilhot F, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99(6):1928–37. 12. 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. N Engl J Med. 2003;348(11):994–1004. 13. Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108(6):1809– 20. 14. 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. N Engl J Med. 2003;348(11):994–1004. 15. Sawyers CL, Hochhaus A, Feldman E, Goldman JM, Miller CB, Ottmann OG, et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood. 2002;99(10):3530–9. 16. Lange T, Günther C, Köhler T, Krahl R, Musiol S, Leiblein S, et al. High levels of BAX, low levels of MRP-1, and high platelets are independent predictors of response to imatinib in myeloid blast crisis of CML. Blood. 2003;101(6):2152–5. 17. Reksodiputro AH, Syafei S, Prayogo N, Karsono B, Rinaldi I, Rajabto W, et al. Clinical characteristics and hematologic responses to Imatinib in patients with chronic phase myeloid leukemia (CML) at Cipto Mangunkusumo Hospital. Acta Med Indones. 2010;42(1):2-5. 18. Faderl S, Talpaz M, Estrov Z, Kantarjian HM. Chronic myelogenous leukemia: biology and therapy. Ann Intern Med. 1999;131(3):207– 19. 19. Morán VP, Baute RG, Facundo JCJ, Ramírez PH, Núñez AA, Martínez EE, et al. Introduction of imatinib as first-line therapy for chronic myeloid leukemia in Cuba. MEDICC Rev. 2011;13(1):35–40. 20. Kantarjian HM, Talpaz M, O’Brien S, Smith TL, Giles FJ, Faderl S, et al. Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-α: Follow-up results. Clin Cancer Res. 2002;8(7):2177–87. 21. Koptyra M, Falinski R, Nowicki MO, Stoklosa T, Majsterek I, Nieborowska-Skorska M, et al. BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance. Blood. 2006;108(1):319–27. 22. Huang M-E, Facca C, Fatmi Z, Baïlle D, Bénakli S, Vernis L. DNA replication inhibitor hydroxyurea alters Fe-S centers by producing reactive oxygen species in vivo. Sci Rep. 2016;6(1):29361. 23. Nakayashiki T, Mori H. Genome-wide screening with hydroxyurea reveals a link between nonessential ribosomal proteins and reactive oxygen species production. J Bacteriol. 2013;195(6):1226–35. 24. Taylor JG, Darari DS, Maric I, McIver Z, Arthur DC. Therapy-Related Acute Myelogenous Leukemia in a Hydroxyurea-Treated Patient With Sickle Cell Anemia. Ann Intern Med. 2011;155(10):722–4.

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.