Increased cardiometabolic traits in pediatric survivors of acute lymphoblastic leukemia treated with total body irradiation

Abstract

Survivors of childhood acute lymphoblastic leukemia (ALL) may face an increased risk of metabolic and cardiovascular late effects. To determine the prevalence of and risk factors for adverse cardiometabolic traits in a contemporary cohort of pediatric ALL survivors, we recruited 48 off-therapy patients in remission treated with conventional chemotherapy and 26 treated with total body irradiation (TBI)-based hematopoietic cell transplantation (HCT) in this cross-sectional pilot study. At a median age of 15 years (range, 8-21 years), HCT survivors were significantly more likely than non-HCT survivors to manifest multiple cardiometabolic traits, including central adiposity, hypertension, insulin resistance, and dyslipidemia. Overall, 23.1% of HCT survivors met the criteria for metabolic syndrome (≥ 3 traits), compared with 4.2% of non-HCT survivors (P = .02). HCT survivors also had increased C-reactive protein and leptin levels and decreased adiponectin, suggestive of underlying inflammation and increased visceral fat. In multivariate analyses, history of HCT remained associated with ≥ 2 traits (odds ratio [OR]. 5.13; 95% confidence interval [CI], 1.54-17.15) as well as with ≥ 3 traits (OR, 16.72; 95% CI, 1.66-168.80). Other risk factors included any cranial radiation exposure and family history of cardiometabolic disease. In summary, pediatric ALL survivors exposed to TBI-based HCT as well as to any cranial radiation may manifest cardiometabolic traits at an early age and should be screened accordingly.

Figure 1

Distribution of selected biomarkers stratified by hematopoietic cell transplantation (HCT) status: adiponectin, leptin, C-reactive protein (CRP), soluble intercellular and vascular cell adhesion molecules (sICAM, sVCAM) and E-selectin. Boxes show median values and interquartile ranges with whiskers denoting upper and lower adjacent values; outside values marked by closed circles. Differences between HCT and non-HCT survivors were significant for adiponectin and CRP (p<0.001 and p=0.02, respectively); distribution of other biomarkers were not significantly different in unadjusted analyses (leptin, p=0.08; sICAM, p=0.17; sVCAM, p=0.96; E-selectin, p=0.19).