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Introduction : Treatment with tyrosine kinase inhibitors (TKIs) has dramatically increased the overall survival of patients with chronic myeloid leukemia (CML) but second generation TKI has been associated with an increased risk of cardiovascular events. Objectives: The aim of this study was to evaluate the incidence of cardiovascular adverse events (CVE) in CML patients treated with TKIs and to correlate with the cardiovascular (CV) risk of the patients. Methods: this is a retrospective analysis of consecutive CML patients treated with TKIs between 2005 and 2013at our Institution. Baseline risk factors for CV diseases were collected at baseline and included age, arterial hypertension (AH), dyslipidemia, obesity, hypothireoidism, smoking, diabetes mellitus (DM), coronary artery disease and chronic renal failure. Cardiovascular events during TKI treatment were collected and included: myocardial infarction, unstable angina, peripheral arterial disease, stroke, arrythmia,hypertension and cardiac failure. Cardiovascular risk was calculated using the SCORE chart of the European Society of Cardiology and patients were classified in low, moderate, high and very high risk. Results: We analyzed CML patients treated with imatinib (n=117), dasatinib (n=91) and nilotinib (n=60). The median time of follow-up was 748, 519 and 851 days, respectively. Baseline risk factors: 90 patients (38,5%) had hypertension, 34 (14,5%) DM, 67 (28,6%) dyslipidemia, 51 (21,8%) obesity, 22 (9,4%) hypothyroidism, 14 (6%) coronary arterial disease, 21 (9%) systolic cardiac dysfunction, 4 (1,7%) stroke, 20 (8,5%) chronic kidney failure and 36 (15,4%) were smokers. SCORE chart classification: 106 patients (39,5%) were in the low-risk category, 70 (26%) in the moderate risk, 46 (17,2%) in the high risk, 46 (17,2%) in the very high risk group. Overall, the cumulative incidence of CVE was 4.1%. Five (5.5%) events occurred during dasatinib treatment (P=0.015), 6 (10%) events during nilotinib and no events during imatinib treatment (P=0.001). The incidence of CVE was 10.8% in the high and very high-risk groups and 0.52% in moderate and low risk group (P≤0.001). The incidence of arterial ischemic events (AIE) was 10% (n=6) in patients treated with nilotinib, 2.2% (n=2) with dasatinib and 0% with imatinib (P≤0.001). Arterial events were exclusively observed in high and very high-risk groups (8 events, 8.7%) (P≤0.001). The risk factors associated with a higher risk of CVE were hypertension (P≤0.001), dyslipidemia (P≤0.001), coronary arterial disease (P=0.003), congestive heart failure (P=0.002) and chronic renal failure (P=0.011). Disease progression was the main cause of death in all groups. Conclusions: CVE were more frequent in patients treated with second generation TKIs. AIE were more frequent in patients treated with nilotinib, in those having a high or very high risk SCORE. The CV risk stratification of CML patients before and during TKI therapy can help in TKI selection and to identify patients at high risk, in order to reduce the morbidity and mortality associated with CVE. Disclosures Pagnano: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Miers-Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

The incidence of Grade 3 (hemoglobin [Hb] level 6.5–8 g/dL) or Grade 4 (Hb level < 6.5 g/dL) anemia was reported to be 3% with imatinib therapy for newly diagnosed CML in the IRIS trial, with a median follow-up of 19 months and 7% for chronic-phase (CP) chronic myeloid leukemia (CML) after IFN-α failure. However, there is few data regarding development of anemia after long-term follow-up and its causes. The aim of this work was to evaluate the incidence of anemia after at least two years of treatment of CML patients in CP treated with imatinib and to identify other contributing causes of anemia in this population. Patients and Methods Between 2006 and 2010 121 patients with CML were treated with imatinib 400-800 mg in our center. Forty-six patients were excluded from the analysis for accelerated phase at diagnosis (n=20), discontinuation of imatinib before 2 years of treatment (n=21) and 5 for other causes. A total of 65 patients were evaluated. Hb levels were analyzed at diagnosis, at imatinib start, and at two years of imatinib. Anemia developed after the second year of imatinib therapy was classified as grade 1 (Hb level < 10.0 g/dL), grade 2 (Hb level of 8.0 to < 10 g/dL), or grade 3 (Hb level of < 8.0 g/dL) for the purpose of treatment evaluation according to National Cancer Institute (NCI) Common Toxicity Criteria - Version 4.0. Other comorbidities were analyzed. Results The median age was 53 years (24-86 years), 34 male (52%). 38% of the patients did not present other medical conditions. Comorbidities found in 62% of the patients: systemic arterial hypertension (31%), diabetes mellitus (6.7%), cardiopathy (5%), hypothyroidism (6.1%) and renal failure (only one patient with renal dysfunction in dialysis). Two patients received interferon: one prior imatinib and another during pregnancy, requiring interruption of imatinib in this period. Patient’s responses: 54 (83%) achieved complete cytogenetic response (CCR) and 10 lost response; eight of them developed anemia; 7 had (10.7%) partial response, 1 minor response (1,5%), 1 no response and 1 was not available. Fifty-three patients (81.5%) achieved major molecular response, with loss of response during follow-up in 8 cases (12.5%), seven of these developed anemia.The median Hb (g/dL) level was 12.1, 13 and 13.2 at diagnosis, at imatinib start and at 2 years of treatment respectively. Most of the patients developed Hb bellow the reference level (73.8%; n = 48) during the follow-up, after the second year of treatment. Anemia classification according to NCI criteria: 41 cases presented grade 1, 6 (12.5%) grade 2 and one grade 3. Of these, 68.7% (n = 33) had no etiological causes for the anemia, five patients (10.4%) were resistant, two (4.2%) were not adherent to treatment and in 8 cases (16.7%) the etiology of anemia was identified: hypothyroidism (n=1), erosive gastritis (Helicobacter Pylori positive)(n=1), B12 vitamin deficiency (n=2), HIV/AIDS (n=1), pulmonary tuberculosis (n=1) and renal failure (n=2). Fourteen (29.2%) patients had normalization of Hb levels without medical intervention and the majority (56.2%) still persists with the anemic status until the last follow-up. Four (8.3%) patients had resolution of the anemia after switching to a second generation inhibitor and 3 (6.2%) showed clinical improvement after treatment of the cause. In summary, several degrees of anemia may occur in patients with CML on long-term imatinib therapy, most of them not severe. Regular hematological follow-up is required to identify causes not CML related that can be corrected or if related to imatinib toxicity, dose modification or change of therapy. It should be emphasized the importance of investigating secondary causes for anemia, especially in patients with good adherence to treatment and satisfactory therapeutic response. Disclosures: No relevant conflicts of interest to declare.