L-arginine – targeted for the anthracycline cardiotoxicity prevention in patients with acute leukemia of high cardiological risk

Abstract

The risk of anthracycline cardiotoxicity (AC) significantly increases in patients with comorbid ischemic heart disease (IHD), which requires monitoring and prevention during chemotherapy (CT) of acute leukemia (AL). Aim: To evaluate the effectiveness of L-arginine in AC prevention in AL patients with comorbid IHD during induction CT. Materials and methods. A total 66 patients with newly diagnosed AL and comorbid IHD were included in the study, ECOG I-II. The cohort consisted of 34 (51.5%) males and 32 (48.5%) females, age 54-72 years. The IHD duration was 3–15 years. CT included doxorubicin. We determined the level of troponin I, nitrite anions [NO2]-, performed daily ECG-monitoring: at baseline and in achieving a cumulative dose of anthracyclines (CDA) from 100 to 200 mg/m2. Depending on AC prevention patients were divided into two groups: (n=36) – AL patients treated with CT; II (n=30) – AL patients treated with CT and L-arginine. Results. Prior to CT, according to the daily ECG-monitoring in 47 (71.2%) patients periods of tachycardia were diagnosed, with single supraventricular extrasystoles (SEs) and ventricular extrasystoles (VEs) – in 35 (53%) and 17 (25.7 %) pts, respectively. The decreased concentration of [NO2]- in blood serum in 1.5 times relative to normal values (p˂0.05) was noticed. Troponin I in all patients of both groups was <0.5 ng/ml. Reaching low CDA in group I we recorded: periods of tachycardia in 36 (100%) pts, increasing number of single and paired SEs – in 24 (66.6%), VEs episodes – in 19 (52%), clinically significant ST-segment depression – in 29 (80.5%) and interval QT prolongation – in 14 (38.8%) pts. Troponin I was >0.5 ng/ml in 7 (19.4%) pts. Simultaneously, deepening of endothelial dysfunction (ED) was noted: [NO2]- was in 1.8 times lower vs norm. After 2 CT courses in 20 (66.6%) patients of group II on tachycardia background the single SEs were recorded and only in 1 (3.3%) patient troponin I level was >0.5 ng/ml. The ED leveled: [NO2]- didn’t significantly differ from the norm. Thus, L-arginine in AL patients with comorbid IHD during induction CT leads to reducing the risk of necrotic injury of cardiomyocytes and improves endothelial function that prevents early AC.