Impact of Nutritional Status as a Risk Factor for Cardiotoxicity in Children with Leukemia

Introduction/Background/Significance: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer in the world. Doxorubicin (Dox) is a very useful drug in these patients, however, one of the main adverse effects caused by the use of Dox is cardiotoxicity (CT). Protein-calorie malnutrition (PCM) is a factor that, among others, can influence the development of CT due to Dox.

Materials and Methods/Case Presentation/Objective: The aim of our study was to associate PCM as a risk factor for CT induced by Dox in Mexican children with ALL.

This is a prospective, descriptive, longitudinal and comparative case-control study of the Pediatric Haemato-Oncology service at the SSA Cancerology State Center (CECAN) in Durango, México. Eighty-nine children (1 to 18 years old) with ALL who were treated with Dox, from October 2018 to July 2023 were included. A total of 89 patients were included. All patients were in the remission induction stage.

All 89 patients with acute lymphoblastic leukemia (ALL) underwent an initial echocardiographic examination to assess for cardiotoxicity (CT), which was found to be normal prior to initiating treatment with doxorubicin (Dox). One month after the first dose of Dox, a second echocardiogram was performed. Subsequent echocardiograms were conducted at 4 months (third), 10 months (fourth), 1.5 years (fifth), 2 years (sixth), and 2.8 years (seventh) following Dox administration.

Cardiotoxicity was defined as a systolic dysfunction characterized by a 5% to 10% decrease in left ventricular ejection fraction (LVEF), or a reduction in fractional shortening (FS) of less than 28%. Diastolic dysfunction was defined by an abnormal E/A ratio (E/A < 1 or > 2). Malnutrition assessment was based on body mass index (BMI) percentiles by age and sex, using the CDC (Centers for Disease Control and Prevention) growth charts. Patients were classified as underweight (< 5th percentile), normal weight (5th–84th), overweight (85th–94th), and obese (≥ 95th). Underweight was considered as presence of PCM. This evaluation was conducted at admission, at the time of cardiotoxicity (CT) diagnosis, and throughout treatment. Weight, height (TANITA WB-3000), and waist circumference were measured. A complete physical examination and clinical history were also performed.

Results/Description/Main Outcome Measures: Of the 89 patients with ALL, 14 developed cardiotoxicity (CT), which was significantly associated with protein-calorie malnutrition (PCM) (p < 0.001). Ten of the 15 patients with PCM presented CT, mostly girls (8/10). All patients with CT showed systolic dysfunction (altered LVEF and FS), and 50% also had diastolic dysfunction (abnormal E/A), especially girls with moderate PCM. Risk analysis revealed a strong association between PCM and CT (OR = 35.5, p = 0.001). Normal BMI was protective (OR = 0.28, p = 0.001). Most CT cases occurred during the maintenance phase of treatment.

Conclusions: This study highlights the impact of PCM on the development of CT in pediatric patients treated with Dox, particularly in girls. Females with PCM showed both systolic and diastolic dysfunction, while males mainly presented systolic damage. Special attention should be given to girls with PCM or at risk, as diastolic dysfunction may precede systolic failure.