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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“…Regarding selective outcome and analysis reporting, some studies do not include the full ALL population available due to the inclusion and exclusion criteria [ 41 , 43 , 44 ]. One glaring difference can be found in a study conducted by Samosir et al [ 43 ] in which only 49 children were included out of 495 newly-diagnosed cases of childhood ALL. Therefore, a separate analysis has been done with the original number of ALL cases before the inclusion and exclusion criteria in these three studies.…”

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“…Surgery and chemotherapy are significant in the battle against hepatocellular carcinoma, saving millions of patients. Daunorubicin (DNR) is a kind of anthracycline used clinically as a chemotherapy reagent, mainly curing cancers such as acute myeloid leukemia, acute lymphoblastic leukemia, and Kaposi’s sarcoma ( Deng et al, 2021 ; Samosir et al, 2021 ; Shepherd et al, 2021 ). However, it is not the first drug of choice for HCC because daunorubicin can be turned into daunorubicinol in the liver with serious cardiac effects.…”