PF267 RISK ASSESSMENT OF ANTHRACYCLINE CARDIOTOXICITY IN PATIENTS WITH ACUTE LEUKEMIA AND CONCOMITANT ISCHEMIC HEART DISEASE
Authors: T. Lymanets, I. Skrypnyk, G. Maslova, I. Gusachenko
Journal: HemaSphere (2019)

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 AL 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 Holter ECG monitoring and considered to be according to CTCAE 4.03 as reduction of left ventricular ejection fraction (LVEF) 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. Results: After induction CT the Holter ECG monitoring has shown an increased number of painless myocardial ischemia periods in 29 (80.5%) pts of subgroup IIA vs 8 (22.2%) before treatment; p < 0.001. QTc prolongation was noticed in 14 (38.8%) pts of subgroup IIA vs 7 (14.9%) of subgroup IA without IHD; p < 0.05. The presence of IHD was a risk factor for AC development, the manifestations of which are prolongation of QTc interval (OR = 3.636; 95% CI = 1.278–10.349; p < 0.05) and QRS voltage decrease (OR = 3.482; 95% CI = 1.270–9.549; p < 0.05). Echocardiography showed LVEF reduction more than 10% of baseline in 13 (36%) pts of subgroup IIA, without a significant difference vs subgroup IA. L-arginine in patients with AL and concomitant IHD has reduced the frequency of “silent ischemia”, according to Holter ECG monitoring, by 40.5%; p < 0.05, QTc interval prolongation–by 28.8%; p < 0.05, and according to echocardiography, LVEF decrease more than 10% of baseline–by 22.7%; p < 0.05. The absence of L-arginine prophylaxis was a risk factor for AC: painless ST segment depression (OR = 6.214; 95% CI = 2.064–18.710; p < 0.05); QTc prolongation (OR = 5.727; 95% CI = 1.458–22.497; p < 0.05) and decreased LVEF more than 10% of baseline (OR = 3.674; 95% CI = 1.049–12.865; p < 0.05). There was no systolic dysfunction in patients with concomitant IHD, who received L-arginine during induction CT. Summary/Conclusion: Our results proved that preventive appointment of L-arginine during induction CT reduces the risk of AC development in patients with AL and concomitant IHD.