Novoa-Gregorio JE, Teixeira-Fernández R

Language: Spanish
References: 20
Page: 69-75
PDF size: 371.67 Kb.

ABSTRACT

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1-2 cases per 100,000 adults and accounts for ~ 15 % of newly diagnosed cases of leukemia in adults. Chronic myeloid leukemia is characterized by a genetic balanced translocation, t (9; 22) (q34 , q11.2), which involves a fusion of the Abelson oncogene (ABL) on chromosome 9q34 with the breakpoint cluster region gene (BCR) on chromosome 22q11. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of the translocation is the generation of a fusion oncogene BCR-ABL, which in turn results in a Bcr-Abl oncoprotein. The first-line therapy: three tyrosine kinase inhibitors (TKI), imatinib, dasatinib and nilotinib have been approved by the Food and Drug Administration (United States of America) for first-line treatment of patients with newly diagnosed CML in chronic phase (CMLCP). Clinical trials with the second generation TKI reported significantly deeper and faster responses; its impact on long-term survival has not yet been determined. Salvage therapy: for patients who do not respond to first-line treatment, second-line options include second and third generation TKI. Although TKI second and third generation are potent and specific, exhibit unique pharmacological properties and response patterns in relation to different patient characteristics, comorbidities, disease stage and BCR-ABL mutation status. For patients who develop the resistance mutation T315I have at this time ponatinib is available. Allogeneic transplantation remains an important therapeutic option for CML-CP who have failed at least 2 TKI, and for all patients of advanced disease.

REFERENCES

1. 1. O’Brien SG, Guilhot FO, Larson RA, Gathmann I, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003;348:994-1004.

2. Bansal S. Is imatinib still the best choice as first-line oral TKI. South Asian J Cancer 2014;3:83-86.

3. Murro H, Goldstein S, Bezares R, Milone G, Bruno S, Novoa JE y Comité de Leucemias Crónicas. Estudio prospectivo estratificado en pacientes con leucemia mieloide crónica según grupo de riesgo al diagnóstico. Protocolo 10-LMC-93, GATLA/GLATHEM, Buenos Aires, 1994.

4. Deininger M, O’Brien SG, Guilhot FO, Goldman JM, 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;114:1126.

5. Mahon FX, Rea D, Guilhot J, Guilhot F, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: The prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 2010;11:1029-1035.

6. Kantarjian HM, Hochhaus A, Saglio G, Souza CD, et al. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosomepositive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol 2011;12:841-851.

7. Kantarjian H, Shah NP, Hochhaus A, Cortes J, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260-2270.

8. Radich JP, Kopecky KJ, Appelbaum FR, Kamel-Reid S, et al. A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic phase chronic myeloid leukemia. Blood 2012;120:3898-3905.

9. Aichberger KJ, Herndlhofer S, Schernthaner GH, Schillinger M, et al. Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in CML. Am J Hematol 2011;86:533-539.

10. Rea D, Gautier JF, Breccia M, et al. Incidence of hyperglycemia by 3 years in patients (Pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with nilotinib (NIL) or imatinib (IM) in ENESTnd. Blood 2012;120:1686.

11. Guilhot F, Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib (versus imatinib) in patients (Pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): analysis of safety and efficacy by use of baseline medications in the DASISION Trial. Blood 2010;116:2295.

12. Montani D, Bergot E, Gunther S, Savale L, et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation 2012;125:2128-2137.

13. Shah NP, Guilhot F, Cortés JE, et al. Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study. Blood 2014;123:2317-2324.

14. Hochhaus A, Saglio G, Larson RA, Kim DW, et al. Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood 2013;121:3703-3708.

15. Shah NP, Kantarjian H, Hochhaus A, Cortés JE, et al. Dasatinib versus imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CMLCP) in the DASISION trial: 18-month follow-up. Blood 2010;116:206.

16. Marin D, Bazeos A, Mahon FX, Eliasson L, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol 2010;28:2381-2388.

17. Baccarani M, Deininger MW, Rosti G, Hochhaus A, et al. European leukemia net recommendations for the management of chronic myeloid leukemia: 2013. Blood 2013;122:872-884.

18. National comprehensive cancer network guidelines version 2. 2012 [Lastaccessedon 2013 Dec 10].

19. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2014 update on diagnosis, monitoring & management. Am J Hematol 2014;89:547-556.

20. Novoa JE, Teixeira R. Tyrosine kinase inhibitors in chronic myeloid leukemia, an update 2014. MD Anderson Bulletin 2014.