Souza CA, Pagnano KB, Bendit I, Conchon M, Freitas CM, Coelho AM, Funke VA, Bernardo WM there are 27% and 15% reductions in the risk of swelling and water retention, respectively with dasatinib 140 mg. However, the risk of neutropenia and thrombocytopenia increases by 22% (NNH: 5) and 42% (NNH: 2), respectively(60)(B). These results remain constant at 18 months of follow-up with an increase in disease-free survival(61)(B). The treatment of these patients (CML in chronic phase, resistant to imatinib) with dasatinib 100 mg/day compared to 140 mg/day leads to a similar clinical response in 6 months and 2 years of follow-up (complete hematologic response, cytogenetic response and disease-free survival), however the risk of pleural effusion is reduced by 9% (NNT: 11), of thrombocytopenia by 15% (NNT: 7) and of discontinuity of treatment(62,63)(A). The response rate of chronic phase CML patients under nilotinib treatment (400 mg b.i.d) is no different to patients resistant or intolerant to imatinib (600 mg/day). The lack of response to imatinib (hematologic or cytogenetic) predicts absence of response to nilotinib(64)(B). Patients who attain a response with nilotinib remain with 96% to 98% of the response (hematologic or cytogenetic) at 6 months of follow-up(65)(B). The mean time to obtain a complete hematologic response is 2.8 months and complete cytogenetic response is 3.2 months, with disease-free survival and overall survival at 24 months being estimated at 64% and 87%, respectively(66)(B). Patients resistant to imatinib or dasatinib treatment attain 79% complete hematologic response and 24% complete cytogenetic response at 12 months(67)(C). In chronic phase CML patients resistant to imatinib and dasatinib, treatment with bosutinib (500 mg/day) produces complete hematological and complete cytogenetic responses in 62% and 31% of the cases, respectively. Patients resistant to imatinib and nilotinib treatment achieve complete hematological and complete cytogenetic responses in 75% and 35% of cases taking bosutinib (500 mg/day). In cases of resistance to imatinib or dasatinib, the likelihood of maintaining response, disease-free survival and overall survival from 12 months on are 27%, 32.4% and 72.9%, respectively. In patients resistant to imatinib and nilotinib treated with bosutinib, the odds of maintaining response, disease-free survival and overall survival from 12 months, are 22.2%, 44.4% and 77.7%, respectively(68)(B). Recommendation: Chronic phase CML patients, who are resistant to imatinib at a dose of 400 mg, should be treated with dasatinib (100 mg/day), nilotinib (800 mg/day) or bosutinib (500 mg/day). Are there differences in the toxicity profiles of second- generation tyrosine kinase inhibitors (dasatinib and nilotinib)? The difference in adverse effects between imatinib with nilotinib or dasatinib is expressed as the NNT; when these latter two drugs produce a reduction in the risk of adverse effects and the number needed to harm (NNH) when the risk of a particular adverse effect increases. 372 The use of nilotinib (at any dose) as first-line therapy of patients with newly diagnosed CML reduces the rates of nausea (NNT: 8), diarrhea (NNT: 7), vomiting (NNT: 6), muscle spasm (NNT: 6), edema (NNT: 11) and neutropenia (NNT: 3) when compared to imatinib. However, the rates of rash (NNH: 4), headache (NNH: 8), pruritus (NNH: 8) and alopecia (NNH: 11) are increased and there are increases in liver enzymes (NNH: 2), total bilirubin (NNH: 2) and glucose (NNH: 5)(43)(A). When nilotinib is given as second-line therapy in chronic phase CML patients, cardiotoxicity can occur with increases in the QT interval (QTc - 1% of cases) and thrombocytopenia (29% of cases)(65)(B). In a comparison of dasatinib and imatinib as first-line therapy for CML, the main non-hematological adverse effects including nausea (NNT: 9), myositis (NNT: 8) and water retention (NNT: 4) are reduced with dasatinib. However, there are increases in pleural effusion in 10% (NNH: 10), thrombocytopenia in 9% (NNH: 11) and cardiotoxicity in 0.4%(41)(B). As second-line therapy in chronic-phase CML patients, dasatinib produces increases in the rates of pleural effusion (NNH: 6), neutropenia (NNH: 5), thrombocytopenia (NNH: 2), dyspnea (NNH: 6) and headache (NNH: 7)(60)(B). Recommendation: With regards to most expected adverse effects using this class of medication, dasatinib and nilotinib have similar results but with slight differences in the degree. However, nilotinib seems to cause more hepatotoxicity and dasatinib causes more water retention (pleural effusion). Does adherence to imatinib treatment have prognostic impact? CML patients on imatinib treatment who have suboptimal response are less adherent to treatment (do not take the medication) than patients with optimal response. Patients treated for more than 12 months who have complete cytogenetic response also have better compliance than those with partial cytogenetic response. There is no difference in the hematologic response between adherent and non-adherent patients(69)(B). There is a direct correlation between adherence (≤ 90% or > 90%) of CML patients to imatinib treatment and the likelihood of major molecular response at 6 years (an increase in 66.1% of response in adherence > 90%). When adherence is less than 80% there is no molecular response. Patients who need to increase the dose of imatinib have 12.8% reduction in adherence(70)(B). In the treatment of CML with imatinib, ≤ 85% adherence increases the risk of loss of complete cytogenetic response by 34.9% (NNH: 3). No patients with adherence ≥ 95% lose cytogenetic response. Patients with adherence level ≤ 85% who never attained molecular response, have low adherence as a predictor of loss of cytogenetic response. Adherence of ≤ 85% reduces the disease-free survival by 37% (NNH: 3). Adherence rates of more than 85% confer a similar prognosis as patients who have major molecular response(71)(B). Rev Bras Hematol Hemoter. 2012;34(5):367-82