Adipokines, Inflammation, and Adiposity in Hematopoietic Cell Transplantation Survivors

Abstract

Adult survivors of acute leukemia in childhood have a higher-than-expected frequency of obesity and are at increased risk for metabolic syndrome and early mortality from cardiovascular disease (CVD). Adipose tissue has been recognized as an endocrine and paracrine organ that secretes various adipokines involved in metabolic regulation and inflammatory processes. In this study, we examined inflammatory factors (IL-6 and TNF-α) and adipokines (adiponectin, leptin), in addition to body composition and adiposity, in cancer survivors who underwent hematopoietic cell transplantation (HCT) during childhood compared with sibling controls. Over 2-year survivors of HCT for hematologic malignancies during childhood were recruited from 2 institutions along with a control population of siblings. Participants underwent evaluation for body composition, anthropometric measurements, and assessment of CVD risk factors and adipokines. Cases were stratified by radiation exposure in the preparative regimen (total body irradiation [TBI] + central nervous system [CNS] irradiation, TBI only, chemotherapy only) and adjusted least squares means were estimated for each adipokine and adjusted by age, sex, race, Tanner stage, and percent fat mass (PFM) percentiles (0-24, 25-74, 75+). A total of 151 HCT survivors and 92 siblings underwent evaluation. Significant differences in mean adipokine levels were detected between survivors and siblings; leptin was significantly higher and adiponectin significantly lower in HCT survivors who received TBI with or without CNS irradiation compared with siblings. IL-6 was significantly higher in all groups of HCT survivors compared with siblings. Body mass index (BMI) was similar in survivors and controls, although PFM was significantly higher in all groups of HCT survivors and lean body mass (LBM) was lower in survivors who received TBI with or without CNS radiation compared with siblings. HCT survivors showed an unfavorable profile of inflammation, adipokines, and adiposity, despite similar BMI as controls. Higher PFM and lower LBM may contribute to these findings. TBI exposure is correlated with greater severity of these observations. Increasing LBM may represent a tangible target for mitigating the high cardiometabolic risks of HCT survivors.