Souza CA, Pagnano KB, Bendit I, Conchon M, Freitas CM, Coelho AM, Funke VA, Bernardo WM 63. Shah NP, Kim DW, Kantarjian H, Rousselot P, Llacer PE, Enrico A, et al. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimalresponse or intolerance to imatinib. Haematologica. 2010;95(2):232-40. 64. Koren-Michowitz M, le Coutre P, Duyster J, Scheid C, Panayiotidis P, Prejzner W, et al. Activity and tolerability of nilotinib: a retrospective multicenter analysis of chronic myeloid leukemia patients who are imatinib resistant or intolerant. Cancer. 2010;116(19):4564-72. 65. Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F, et al. Nilotinib (formerlyAMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective inpatients with Philadelphia chromosome- positive chronic myelogenous leukemia inchronic phase following imatinib resistance and intolerance. Blood. 2007;110(10):3540-6. 66. Kantarjian HM, Giles FJ, Bhalla KN, Pinilla-Ibarz J, Larson RA, Gattermann N, et al. Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase afterimatinib resistance or intolerance: 24-month follow-up results. Blood. 2011;117(4):1141-5. 67. Giles FJ, Abruzzese E, Rosti G, Kim DW, Bhatia R, Bosly A, et al. Nilotinib is active in chronic and accelerated phase chronic myeloid leukemiafollowing failure of imatiniband dasatinib therapy. Leukemia. 2010;24(7):1299-301. 68. Khoury HJ, Cortes JE, Kantarjian HM, Gambacorti-Passerini C, Baccarani M, Kim DW, et al. Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood. 2012;119(15):3403-12. 69. Noens L, van Lierde MA, De Bock R, Verhoef G, Zachée P, Berneman Z, Martiat P, Mineur P, Van Eygen K, MacDonald K, De Geest S, Albrecht T, Abraham I. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood. 2009;113(22):5401-11. 70. Marin D, Bazeos A, Mahon FX, Eliasson L, Milojkovic D, Bua M, 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(14):2381-8. 71. Ibrahim AR, Eliasson L, Apperley JF, Milojkovic D, Bua M, Szydlo R, et al. Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy. Blood. 2011;117(14):3733-6. 72. Ganesan P, Sagar TG, Dubashi B, Rajendranath R, Kannan K, Cyriac S, et al. Nonadherence to imatinib adversely affects event free survival in chronic phase chronic myeloid leukemia. Am J Hematol. 2011;86(6):471-4. 73. Jabbour E, Kantarjian H, O’Brien S, Shan J, Garcia-Manero G, Wierda W, et al. Predictive factors for outcome and response in patients treated with second-generation tyrosine kinase inhibitors for chronic myeloid leukemia in chronic phase after imatinib failure. Blood. 2011;117(6):1822-7. Comment in: Blood. 2011; 117(6):1773-4. 74. Branford S, Rudzki Z, Walsh S, Parkinson I, Grigg A, Szer J, et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood. 2003;102(1):276-83. 75. Soverini S, Martinelli G, Rosti G, Bassi S, Amabile M, Poerio A, et al. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia. J Clin Oncol. 2005;23(18):4100-9. 76. Jabbour E, Kantarjian H, Jones D, Talpaz M, Bekele N, O’Brien S, et al. Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia. 2006;20(10):1767-73. 77. Khorashad JS, de Lavallade H, Apperley JF, Milojkovic D, Reid AG, Bua M, et al. Finding of kinase domain mutations in patients with chronic phase chronic myeloid leukemia responding to imatinib may identify those at high risk of disease progression. J Clin Oncol. 2008;26(29):4806-13. 78. Jabbour E, Jones D, Kantarjian HM, O’Brien S, Tam C, Koller C, et al. Long-term outcome of patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors after imatinib failure is predicted by the in vitro sensitivity of BCR-ABL kinase domain mutations. Blood. 2009;114(10):2037-43. 79. Ono T, Miyawaki S, Kimura F, Kanamori H, Ohtake S, Kitamura K, Fujita H, Sugiura I, Usuki K, Emi N, Tamaki S, Aoyama Y, Kaya H, Naoe T, Tadokoro K, Yamaguchi T, Ohno R, Ohnishi K; Japan Adult Leukemia Study Group. BCR-ABL1 mutations in patients with imatinib-resistant Philadelphia chromosome-positive leukemia by use of the PCR-Invader assay. Leuk Res. 2011;35(5):598-603. 80. Kim TD, Türkmen S, Schwarz M, Koca G, Nogai H, Bommer C, et al. Impact of additional chromosomal aberrations and BCR-ABL kinase domain mutations on the response to nilotinib in Philadelphia chromosome-positive chronic myeloid leukemia. Haematologica. 2010;95(4):582-8. 81. Müller MC, Cortes JE, Kim DW, Druker BJ, Erben P, Pasquini R, et al. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations. Blood. 2009;114(24):4944-53. Comment in: Blood. 2009;114(24):4914-5. 82. O’Hare T, Eide CA, Deininger MW. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood. 2007;110(7):2242-9. 83. Redaelli S, Piazza R, Rostagno R, Magistroni V, Perini P, Marega M, et al. Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol. 2009;27(3):469-71. Comment in: J Clin Oncol. 2010;28(11):e169-71; author reply e172. 84. Hughes T, Saglio G, Branford S, Soverini S, Kim DW, Müller MC, et al. Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase. J Clin Oncol. 2009;27(25):4204-10. 85. Branford S, Melo JV, Hughes TP. Selecting optimal second-line tyrosine kinase inhibitor therapy for chronic myeloid leukemia patients after imatinib failure: does the BCR-ABL mutation status really matter? Blood. 2009;114(27):5426-35. 86. Parker WT, Lawrence RM, Ho M, Irwin DL, Scott HS, Hughes TP, et al. Sensitive detection of BCR-ABL1 mutations in patients with chronic myeloid leukemia after imatinib resistance is predictive of outcome during subsequent therapy. J Clin Oncol. 2011;29(32):4250-9. 87. Wang L, Pearson K, Pillitteri L, Ferguson JE, Clark RE. Serial monitoring of BCR-ABL by peripheral blood real-time polymerase chain reaction predicts the marrow cytogenetic response to imatinib mesylate in chronic myeloid leukaemia. Br J Haematol. 2002;118(3):771-7. 88. Hughes TP, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley ML, Gathmann I, Bolton AE, van Hoomissen IC, Goldman JM, Radich JP; International Randomised Study of Interferon versus STI571 (IRIS) Study Group. Frequency of Major Molecular Responses to Imatinib or Interferon Alfa plus Cytarabine in Newly Diagnosed Chronic Myeloid Leukemia. N Engl J Med. 2003;349(15):1423-32. Comment in: N Engl J Med. 2003;349(15):1399-401. 89. Branford S, Fletcher L, Cross NC, Müller MC, Hochhaus A, Kim DW, et al. Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials. Blood. 2008;112(8):3330-8. 378 Rev Bras Hematol Hemoter. 2012;34(5):367-82