Risk assessment of anthracycline cardiotoxicity in patients with acute leukemia and concomitant ischemic heart disease

Abstract

Background: Great attention has recently been focused on the problem of chemotherapy (CT) complications in patients with acute leukemia (AL). Notable among them is the anthracycline cardiotoxicity (AC), the development of which greatly inhibits the carrying out of CT in full doses, which significantly reduces the patients’ chances for life. The presence of concomitant ischemic heart disease (IHD) potentiates the formation of AC, increases the risk of myocardial injury development. Aims: To assess the risk factors of AC development on low cumulative doses of anthracycline antibiotics (AA) and to increase the efficacy of AC prevention in patients with AI, taking into account concomitant IHD. Methods: The study involved 147 patients with newly diagnosed AL, 72 (49%) males and 75 (51%) females, mean age 54.7 ± 9.3 years, ECOG I-II. All patients were treated in hematology department of Poltava Regional Clinical Hospital n.a.M.V.Sklifosovsky. Depending on the IHD presence, the patients were divided into two groups: I (n = 81)-AL pts without concomitant cardiovascular diseases; II (n = 66)-AL pts with IHD. Due to ongoing AC prevention with L-arginine patients of both groups were further subdivided: IA (n = 47) and IIA (n = 36)—pts receiving CT; IB (n = 34) and IIB (n = 30)-pts, who received CT with prophylaxis of AC with L-arginine. The study was approved by the local ethical committee and all patients and all patients signed the inform consent before they were included. The examination was carried out twice: at baseline and after induction CT, when remission was achieved and AA low cumulative doses <200 mg/m2 were reached. The cardiotoxic effect of AA was evaluated by echocardiography and ITolter ECG monitoring and considered to be according to CTCAE 4.03 as reduction of left ventricular ejection fraction (l.VF.F) more than 10% of baseline and QTc prolongation exceeded 450ms. The episodes of “silent ischemia” were assessed on the basis of ST segment depression by 1 mm or more in the absence of typical pain syndrome.