Risk Factors of Daunorubicine Induced Early Cardiotoxicity in Childhood Acute Lymphoblastic Leukemia: A Retrospective Study

Abstract

Background: Daunorubicine, a type of anthracycline, is a drug commonly used in cancer chemotherapy that increases survival rate but consequently compromises with cardiovascular outcomes in some patients. Thus, preventing the early progression of cardiotoxicity is important to improve the treatment outcome in childhood acute lymhoblastic leukemia (ALL). Objective: The present study aimed to identify the risk factors in anthracycline-induced early cardiotoxicity in childhood ALL. Methods: This retrospective study was conducted by observing ALL-diagnosed children from 2014 to 2019 in Dr. Soetomo General Hospital. There were 49 patients who met the inclusion criteria and were treated with chemotherapy using Indonesian Childhood ALL Protocol 2013. Echocardiography was performed by pediatric cardiologists to compare before and at any given time after anthracycline therapy. Early cardiotoxicity was defined as a decline of left ventricle ejection fraction (LVEF) greater than 10% with a final LVEF < 53% during the first year of anthracycline administration. Risk factors such as sex, age, risk stratification group, and cumulative dose were identified by using multiple logistic regression. Diagnostic performance of cumulative anthracycline dose was evaluated by receiver operating characteristic (ROC) curve. Results: Early anthracycline-induced cardiotoxicity was observed in 5 out of 49 patients. The median cumulative dose of anthracycline was 143.69±72.68 mg/m 2 . Thirty-three patients experienced a decreasing LVEF. The factors associated with early cardiomyopathy were age of ≥ 4 years (PR= 1.128; 95% CI: 1.015-1.254; p= 0.001), high risk group (PR= 1.135; 95% CI: 1.016-1.269; p= 0.001), and cumulative dose of ≥120 mg / m 2 (CI= 1.161; 95% CI:1.019-1.332). Conclusion: Age of ≥ 4 years, risk group, and cumulative dose of ≥120 mg/m 2 are significant risk factors for early cardiomyopathy in childhood ALL.

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Assessment of Cardiovascular Function in Childhood Leukemia Survivors: The Role of the Right Heart

“…Therefore, the majority of ALL children are expected to become long-term survivors, although, unfortunately, many of them are still likely to experience adverse late effects related to chemotherapies [ 2 , 3 , 4 , 5 , 6 , 7 ]. The high incidence of cardiotoxicity is well-documented in long-term childhood ALL survivors who underwent anthracycline treatment, especially doxorubicin and daunorubicin [ 8 , 9 , 10 ]. Anthracyclines promote myocardial injury by inducing myocyte morphology and functional alterations, myocardial sarcoplasmic reticulum damage, and mitochondria vacuolization which can negatively impact on left ventricular (LV) function and compliance [ 11 , 12 , 13 ].…”