Cardiotoxicity: A Major Setback in Childhood Leukemia Treatment

Abstract

Ongoing research in the field of pediatric oncology has led to an increased number of childhood cancer survivors reaching adulthood. Therefore, ensuring a good quality of life for these patients has become a rising priority. Considering this, the following review focuses on summarizing the most recent research in anthracycline-induced cardiac toxicity in children treated for leukemia. For pediatric cancers, anthracyclines are one of the most used anticancer drugs, with over half of the childhood cancer survivors believed to have been exposed to them. Anthracyclines cause irreversible cardiomyocyte loss, leading to chronic, progressive heart failure. The risk of developing cardiotoxicity has been known to increase with the treatment-free interval and total cumulative dose. However, because of individual variations in anthracycline metabolism, it has recently been shown that there is no risk-free dose. Moreover, studies have shown that diagnosing anthracycline-induced cardiomyopathy in the symptomatic phase is associated with poor treatment response and prognosis. Thus, early and systematic evaluation of these patients is crucial to allow optimal therapeutic intervention. Although currently echocardiographic assessment of left ventricle ejection fraction and cardiac biomarker evaluation are being used for cardiac function monitoring in oncologic patients, there is no established follow-up and treatment protocol for these patients, and these methods are neither specific nor sensitive for identifying early cardiac dysfunction. All things considered, the need for ongoing research in the field of pediatric cardiooncology is crucial to offer these patients a chance at a good quality of life as adults.

Omega 3 fatty acids can reduce early doxorubicin‐induced cardiotoxicity in children with acute lymphoblastic leukemia

“…Oxidative stress is a central mechanism in doxorubicin-induced cardiac dysfunction, as doxorubicin increases the mitochondrial production of ROS with the accumulation of ROS in the myocardium, leading to DNA and protein damage, membrane lipid peroxidation, and mitochondrial dysfunction. 3,20,31 In addition, the myocardium has a moderately low level of antioxidant defenses and is highly susceptible to doxorubicin-induced cytotoxicity through oxidative stress. 32 In the present study, the cardiotoxicity of doxorubicin was evaluated by echocardiography and biochemical markers of cardiac injury including TPI, CK-MB, and NT-proBNP, which are markers of myocardial cell injury, ventricular dysfunction, and cardiomyocytes necrosis of different etiologies including doxorubicin-induced cardiotoxicity.…”

“…DCT is described as earlyonset toxicity if cardiac manifestations occurred within 1 year of ending the chemotherapy, and it is considered as late-onset toxicity if cardiac symptoms appeared after more than 1 year of stopping chemotherapy. 3,4 Several mechanisms have been implicated in the pathophysiology of DCT, such as apoptosis, mitochondrial dysfunction, and increased oxidative stress. However, the main pathophysiological mechanism of DCT is suggested to be related to oxidative stress and increased production of intracellular reactive oxygen species (ROS) in cardiomyocytes, leading to abnormalities in cardiac contractile function and myocardial cell injury.…”

“…However, the main pathophysiological mechanism of DCT is suggested to be related to oxidative stress and increased production of intracellular reactive oxygen species (ROS) in cardiomyocytes, leading to abnormalities in cardiac contractile function and myocardial cell injury. [3][4][5][6] Early doxorubicin-induced cardiac damage can be detected by elevated cardiac biomarkers including troponin I (TnI), creatine kinase-MB (CK-MB), and N-terminal pro-brain natriuretic peptide (NT-proBNP). [7][8][9][10] Measurement of endogenous antioxidant defense including glutathione and superoxide dismutase enzyme (SOD) and measurement of malondialdehyde (MDA), which is a product of polyunsaturated fatty acid peroxidation, can reflect the oxidative stress status in cancer patients.…”

High-Sensitivity Troponin: A Review on Characteristics, Assessment, and Clinical Implications

“…In this setting, both I and T cardiac troponins were shown to have an important prognostic role, being able to predict up to 3 months ahead the development of a decrease in LVEF, but there is still important controversy regarding this topic. As several studies demonstrated the role of elevations of high-sensitive cardiac troponin-I in predicting subclinical cardiomyocyte damage, other small studies proved a very low sensitivity for subclinical heart disease when troponin T was used [ 60 , 61 ]. What is more, as hs-cTnI levels can be elevated in up to 13.1% of healthy children, many studies suggest the need of using adjusted cuts-off values for this patients [ 62 ].…”

Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies

“…One of the most concerning side effects of CT is cardiotoxicity which can vary from subclinical myocardial dysfunction to irreversible and often fatal heart failure [ 45 ]. It is induced in a dose-dependent manner primarily by anthracyclines which are widely used for therapeutic intervention in probably more than 50% of all childhood cancer patients posing them with an elevated risk for cardiomyopathies in their later life [ 46 ].…”