Study of Metabolic Syndrome in Adolescent and Young Adult Survivors of Childhood Leukemia Who Have Undergone Stem Cell Transplant

• Comparison of the prevalence of metabolic syndrome in adolescent and young adult survivors of childhood leukemia who have undergone hematopoietic stem cell transplantation (HSCT) with age- and gender-matched controls [ Time Frame: ≥2 years post-HSCT ] [ Designated as safety issue: No ]
  
• Comparison of insulin resistance in patients with age- and gender-matched controls [ Time Frame: ≥2 years post-HSCT ] [ Designated as safety issue: No ]
  
• Correlation between insulin sensitivity and risk factors associated with metabolic syndrome [ Time Frame: ≥2 years post-HSCT ] [ Designated as safety issue: No ]
  
• Influence of time since transplant on insulin resistance [ Time Frame: ≥2 years post-HSCT ] [ Designated as safety issue: No ]
  
• Peak growth hormone secretion in patients with insulin resistance and in those without [ Time Frame: ≥2 years post-HSCT ] [ Designated as safety issue: No ]
  
• Growth hormone deficiency in patients with metabolic syndrome and in those without [ Time Frame: ≥2 years post-HSCT ] [ Designated as safety issue: No ]
  
• Association of interleukin-6, tumor necrosis factor-α, C-reactive protein, and leptin with insulin resistance and central obesity [ Time Frame: ≥2 years post-HSCT ] [ Designated as safety issue: No ]
  
• Correlation of adiponectin with insulin resistance and central obesity [ Time Frame: ≥2 years post-HSCT ] [ Designated as safety issue: No ]
  
• Differences in markers for endothelium dysfunction and early indicators of cardiovascular disease [ Time Frame: ≥2 years post-HSCT ] [ Designated as safety issue: No ]
  
• Difference in important health behaviors related to obesity and cardiovascular disease between patients with metabolic syndrome and those without [ Time Frame: ≥2 years post-HSCT ] [ Designated as safety issue: No ]
  

OBJECTIVES:

• To determine the prevalence of metabolic syndrome in adolescent and young adult survivors of childhood leukemia who have undergone hematopoietic stem cell transplantation (HSCT) and compare the extent to which prevalence is higher in HSCT survivors than in age- and gender-matched population norms derived from the Third National Health and Nutrition Examination Survey (NHANES III).
• To evaluate the relationship between insulin resistance and risk factors associated with metabolic syndrome (e.g., hypertension, obesity, hyperinsulinemia, and dyslipidemia) as measured by euglycemic insulin clamp, fasting serum insulin, glucose, lipids (total cholesterol, triglycerides, LDL-C, and HDL-C), blood pressure and anthropometric measurements, and DEXA scan in these patients and compare to age- and gender-matched population norms.
• To assess the extent to which prevalent obesity and insulin resistance are correlated with other factors that have been identified in the causal pathway associated with the development of metabolic syndrome and that may be altered after HSCT, including growth hormone secretion, adipokines (adiponectin and leptin), and inflammatory mediators (interleukin-6, tumor necrosis factor-α, and C-reactive protein).
• To evaluate the association of metabolic syndrome and early signs of impaired endothelial function and cardiovascular changes.
• To evaluate health behaviors related to prevention of cardiovascular disease, diabetes, and obesity, including a physical activity assessment, a dietary assessment, and a health knowledge assessment that will be used in the analyses of metabolic syndrome, growth hormone deficiency, and indicators of cardiovascular disease.

OUTLINE: Patients are stratified according to post-transplant follow-up period (2-9 years vs 10-15 years vs > 15 years).

Patients and their siblings undergo physical examination, a review of medical and family history, and blood pressure and anthropometric measurements. Patients and their siblings also undergo blood sample collection for laboratory studies (including analysis of C-reactive protein and CBC; lipid profile and triglycerides; leptin and adipokines; free thyroxine, TSH, IGF1, IGF3, and LH; and estradiol [females] or testosterone [males]); urine sample collection for microalbumin determination; and other study procedures (including euglycemic insulin clamp study; body composition and bone density [DEXA] study; bone-age x-ray [for patients < 18 years of age]; and vascular studies). Patients also undergo growth hormone stimulation testing.

Patients and their siblings complete questionnaires about their physical activity, dietary habits, and health knowledge.

PROJECTED ACCRUAL: A total of 193 childhood leukemia survivors and 193 healthy siblings will be accrued for this study.