High Prevalence of Metabolic Syndrome Traits in Children with Acute Lymphoblastic Leukemia Entering Maintenance Therapy.
Authors: Esbenshade Adam J. , Koyama Tatsuki , Simmons Jill H. , Whitlock James A. , Friedman Debra L. 
Published: October 2019

Abstract
Abstract 4114
The metabolic syndrome, which includes obesity, hypertension, dyslipidemia, and insulin resistance, has been reported to occur in excess among long term survivors of pediatric acute lymphoblastic leukemia (ALL). Among known risk factors are exposure to corticosteroids and cranial radiotherapy. However, at what point along the trajectory of therapy that the metabolic abnormalities develop is unclear. Twenty-two consecutively enrolled patients with pre-B or T cell ALL treated on or according to Children's Oncology Group protocols at Vanderbilt Children's Hospital were evaluated for components of the metabolic syndrome at the start of maintenance chemotherapy. The overall prevalence of metabolic syndrome traits in this cohort was high, with 19 (86%) subjects exhibiting at least 1 component of the metabolic syndrome. Of those, 4 (21%) met full criteria for metabolic syndrome (demonstrating at least 3/5 components) (Table 1). Dyslipidemia was common with 11/22 (50%) having a fasting HDL ≤ 40mg/dl [median= 35mg/dl; 1st/3rd quartiles (29, 38)] and 8/22 (36%) having fasting triglycerides >110 mg/dl [median=165mg/dl; (129, 340)]. Patients with ALL NCI high risk classification had higher fasting triglycerides (p<0.01) and lower HDL (p=0.02) versus those who were classified as standard risk. Hypertriglyceridemia, but not HDL, was correlated with increased patient age (Spearman's ρ=0.45; p=0.03); neither was associated with sex or other components of the metabolic syndrome. Obesity was noted in 6/22 patients (27%) with BMI ≥ 90th percentile, controlled for age and sex. Hypertension was also frequent, observed in 11/22 (50%) subjects. Elevated systolic blood pressure correlated with decreasing age (ρ=-0.45, p=0.03) but not with other components of the metabolic syndrome. Only 1 subject had fasting hyperglycemia. Fasting leptin levels [median=2.6μg/ml (0.9, 4.4)] were significantly correlated with the BMI z-score (ρ=0.44, p=0.05) but did not significantly correlate with other components of the metabolic syndrome. Fasting adiponectin levels [median=21 μg/ml; (13, 25)] did not significantly correlate with any of the components of the metabolic syndrome. No subject had growth hormone deficiency. In summary, although the sample size was small, components of the metabolic syndrome were common at the start of maintenance chemotherapy, prior to significant further exposure to corticosteroids. Dyslipidemia was particularly common, and routine screening may be considered as there is the potential for successful intervention. The patients in this cohort are currently being followed longitudinally during maintenance chemotherapy to assess for changes in metabolic abnormalities with ongoing leukemia therapy, particularly corticosteroids. Determining the nature and onset of metabolic abnormalities can further inform future interventions to prevent or mitigate the abnormalities which, if untreated, may lead to long-term chronic health conditions that may increase cardiovascular risk.
Table 1 Characteristics of subjects meeting at least 3 of 5 criteria for the metabolic syndrome (Cook Criteria*) Subjects 1 2 3 4 Age (years) 14 8 16 6 Gender Female Male Male Male ALL Risk Classification High High High Standard BMI Z-Score at Diagnosis 2.15 2.08 2.39 -0.16 BMI Z-Score at Start of Maintenance 2.24 2.23 2.68 -0.08 Fasting Triglycerides (mg/dl) 352 288 153 336 Fasting HDL (mg/dl) 27 36 35 18 Systolic BP Z-Score -0.13 2.44 0.70 0.77 Diastolic BP Z-Score 0.82 1.76 1.34 1.44 Fasting Glucose (mg/dl) 73 75 86 78 Fasting Leptin (μg/ml) 40.2 19.4 45.7 1.4 Fasting Adiponectin (μg/ml) 27 10 11 21 IGF-1 (ng/ml) 211 288 153 41 *Cook et al. Arch Pediatr Adolesc Med 2003

Disclosures:
No relevant conflicts of interest to declare.