Data are limited in developing countries regarding the clinicopathologic features and response to therapy of chronic myeloid leukemia (CML) in the era of imatinib (IM). The objective of this study is to report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400 mg daily as frontline therapy, and to determine imatinib’s efficacy and safety. From October 2002 to December 2014, 410 CML patients were treated with IM in six Tunisian departments of hematology. Response (hematologic, cytogenetic, and molecular responses) and outcome—overall survival (OS), event-free survival (EFS), and progression-free survival (PFS)—were evaluated. The following prognostic factors were analyzed for their impact on the European leukemia net (ELN) response, OS, EFS, and PFS at 5 years: age, sex, leukocyte count, Sokal score, European Treatment and Outcome Study (EUTOS) score, CML phase, time to starting IM, and impact of adverse events. The median age was 45 years (3–85 years). Two hundred ten (51.2%) patients were male. Splenomegaly was present in 322 of the 410 (79%). Additional cytogenetic abnormalities were encountered in 25 (6.3%) patients. At diagnosis, 379 (92.4%) patients were in CP, 31 (7.6%) were in AP. The Sokal risk was low in 87 (22.5%), intermediate in 138 (35.7%), and high in 164 patients (41.9%). The EUTOS risk was low in 217 (74%), and high in 77 (26%) patients. The rates of cumulative complete cytogenetic response (CCyR), major molecular response (MMR), and molecular response 4/5 log (MR4.5) in CP/AP-CML patients were 72, 68.4, and 46.4%, respectively. The median time to reach CCyR, MMR, and MR4.5 was 6 months (3–51), 18 months (3–72), and 24 months (3–100), respectively. According to the ELN criteria, optimal, suboptimal response, and failure were noted in 206 (51.8%), 61 (15.3%), and 125 (31.4%) patients, respectively. Five-year event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) were 81, 90, and 90%, respectively. By multivariate analysis, AP, high EUTOS risk, and baseline WBC ≥ 150G/l remained independent predictive factors of non-optimal response to IM. The adverse events (AE) of IM were moderate and tolerable. With the caveats that the monitoring of the disease was not optimal, response rates were similar to those reported in previous studies. It is clear to us that improvements should be made in treatment of AP-CML and high Sokal risk group of CP-CML. The frontline use of second-generation tyrosine kinase inhibitor (TKI) is expected to improve the results of the first-line treatment of these high-risk Tunisian patients, but cost and accessibility of this therapy remain the problems in developing countries.
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Aziz Z, Iqbal J, Akram M, Saeed S (2007) Treatment of chronic myeloid leukemia in the imatinib era perspective from a developing country. Cancer 109(6):1138–1145. https://doi.org/10.1002/cncr.22498
Dong-Wook K, Shripad DB, Udomsak B et al (2010) Chronic myeloid leukemia in the Asia-Pacific region: current practice, challenges and opportunities in the targeted therapy era. Leuk Res 34:1459–1471
Cortes JE, Talpaz M, O’Brien S et al (2006) Staging of chronic myeloid leukemia in the imatinib era: an evaluation of the World Health Organization proposal. Cancer 106(6):1306–1315. https://doi.org/10.1002/cncr.21756
Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, Apperley J, Cervantes F, Cortes J, Deininger M, Gratwohl A, Guilhot F, Horowitz M, Hughes T, Kantarjian H, Larson R, Niederwieser D, Silver R, Hehlmann R, European LeukemiaNet (2006) Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European Leukemia Net. Blood 108(6):1809–1820. https://doi.org/10.1182/blood-2006-02-005686
Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, Cervantes F, Deininger M, Gratwohl A, Guilhot F, Hochhaus A, Horowitz M, Hughes T, Kantarjian H, Larson R, Radich J, Simonsson B, Silver RT, Goldman J, Hehlmann R, European LeukemiaNet (2009) Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. JCO 27(35):6041–6051. https://doi.org/10.1200/JCO.2009.25.0779
Baccarani M, Deininger MW, Rosti G et al (2013) European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 122(6):872–884. https://doi.org/10.1182/blood-2013-05-501569
Rohrbacher M, Hasford J (2009) Epidemiology of chronic myeloid leukaemia. Best Pract Res Clin Haematol 22(3):295–302. https://doi.org/10.1016/j.beha.2009.07.007
Funke VA, Medeiro CR, Lima DH et al (2005) Therapy of chronic myeloid leukemia with imatinib mesylate in Brazil: a study of 98 cases. Rev Bras Hematol Hemoter 27:159–165
Aguayo A, Garcia-Alvarez E, Cazares-Ordonez Y, Crespo-Solis E, Martinez-Baños D, Guadarrama-Beltran E, Cervera-Ceballos EE, Lopez-Karpovitch X (2008) Chronic myeloid leukemia: a clinicoepidemiologic and therapeutic description of a single institution in Mexico City. Clin Leuk 2(4):261–266. https://doi.org/10.3816/CLK.2008.n.036
O’Brien SG, Guilhot F, Larson RA et al (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348(11):994–1004. https://doi.org/10.1056/NEJMoa022457
Druker BJ, Guilhot F, O’Brien SG et al (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355(23):2408–2417. https://doi.org/10.1056/NEJMoa062867
Kantarjian HM, O’Brien S, Cortes J et al (2003) 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 98(12):2636–2642. https://doi.org/10.1002/cncr.11831
Rodrigues Lemos JA, Quinto Bentes A, Simões Beltrão AC et al (2010) Late diagnosis and delayed treatment combined as a cause of suboptimal response to imatinib in chronic myeloid leukemia in developing countries, 116. Blood, Dent Abstr 4750
Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G, Guilhot F, Porkka K, Ossenkoppele G, Lindoerfer D, Simonsson B, Pfirrmann M, Hehlmann R (2011) Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood 118(3):686–692. https://doi.org/10.1182/blood-2010-12-319038
Zelada J, Capurro MPA, Rojas B et al (2013) Is EUTOS score predictive of outcome in patients with early chronic phase chronic myeloid leukemia treated with imatinib? Preliminary data from the National Protocol of the Chilean Cooperative Group Panda. Blood 122(21):5196
Oyekunle AA, Osho PO, Aneke JC et al (2012) The predictive value of the Sokal and Hasford scoring systems in chronic myeloid leukaemia in the imatinib era. J Hematol Malig 2:25–32
Tauchi T, Kizakib M, Okamotoc S et al (2011) Seven-year follow-up of patients receiving imatinib for the treatment of newly diagnosed chronic myelogenous leukemia by the TARGET system. Leuk Res 35(5):585–590. https://doi.org/10.1016/j.leukres.2010.10.027
Kantarjian HM, Larson RA, Cortés JE, Deering KL, Mauro MJ (2013) Current practices in the management of chronic myeloid leukemia. Clin Lymphoma Myeloma Leuk 13(1):48–54. https://doi.org/10.1016/j.clml.2012.07.009
Hehlmann R, Lauseker M, Jung-Munkwitz S, Leitner A, Müller MC, Pletsch N, Proetel U, Haferlach C, Schlegelberger B, Balleisen L, Hänel M, Pfirrmann M, Krause SW, Nerl C, Pralle H, Gratwohl A, Hossfeld DK, Hasford J, Hochhaus A, Saußele S (2011) Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-α in newly diagnosed chronic myeloid leukemia. J Clin Oncol 29(12):1634–1642. https://doi.org/10.1200/JCO.2010.32.0598
Lapusan S, Yong A, Savani BN et al (2014) Achieving early molecular response in chronic myeloid leukemia in chronic phase to reduce the risk of progression: clinical relevance of the 3- and 6-month time points. Eur J Haematol 95:103–111
Jain P, Kantarjian H, Nazha A, O'Brien S, Jabbour E, Romo CG, Pierce S, Cardenas-Turanzas M, Verstovsek S, Borthakur G, Ravandi F, Quintas-Cardama A, Cortes J (2013) Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: results with four tyrosine kinase inhibitor modalities. Blood 121(24):4867–4874. https://doi.org/10.1182/blood-2013-03-490128
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Ben Lakhal, R., Ghedira, H., Bellaaj, H. et al. Chronic myeloid leukemia patients in Tunisia: epidemiology and outcome in the imatinib era (a multicentric experience). Ann Hematol 97, 597–604 (2018). https://doi.org/10.1007/s00277-017-3224-2
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