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

Metabolic Syndrome Following Transplant for Leukemia

RATIONALE: Gathering information about how often metabolic syndrome occurs in young survivors of childhood leukemia who have undergone stem cell transplant may help doctors learn more about the disease and the long-term effects of leukemia treatment. It may also help improve the quality of life for future cancer survivors.

PURPOSE: This clinical trial is studying metabolic syndrome in adolescent and young adult survivors of childhood leukemia who have undergone stem cell transplant.

Study Overview

• Status: Completed
• Conditions: Leukemia; Metabolic Syndrome; Long-term Effects Secondary to Cancer Therapy in Children; Cardiovascular Complications

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 244

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98105
      • Clinical Research Center - Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Childhood leukemia survivors and healthy siblings, 9-21 years of age.

Description

DISEASE CHARACTERISTICS:

• Meets 1 of the following criteria:

  • Survivor of childhood leukemia, meeting all of the following criteria:

    • 21 years of age and under at diagnosis
    • Has undergone hematopoietic stem cell transplantation (HSCT) at Fairview University Medical Center or Fred Hutchinson Cancer Research Center ≥ 2 years ago
    • Disease in remission
  • Healthy sibling of a childhood leukemia survivor

PATIENT CHARACTERISTICS:

• Not pregnant
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	≥2 years post-HSCT
Comparison of insulin resistance in patients with age- and gender-matched controls	≥2 years post-HSCT
Correlation between insulin sensitivity and risk factors associated with metabolic syndrome	≥2 years post-HSCT
Influence of time since transplant on insulin resistance	≥2 years post-HSCT
Peak growth hormone secretion in patients with insulin resistance and in those without	≥2 years post-HSCT
Growth hormone deficiency in patients with metabolic syndrome and in those without	≥2 years post-HSCT
Association of interleukin-6, tumor necrosis factor-α, C-reactive protein, and leptin with insulin resistance and central obesity	≥2 years post-HSCT
Correlation of adiponectin with insulin resistance and central obesity	≥2 years post-HSCT
Differences in markers for endothelium dysfunction and early indicators of cardiovascular disease	≥2 years post-HSCT
Difference in important health behaviors related to obesity and cardiovascular disease between patients with metabolic syndrome and those without	≥2 years post-HSCT

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: K S Baker, MD, MS, Fred Hutchinson Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: June 12, 2009
• First Submitted That Met QC Criteria: June 12, 2009
• First Posted (Estimate): June 15, 2009

Study Record Updates

• Last Update Posted (Estimate): December 3, 2012
• Last Update Submitted That Met QC Criteria: November 29, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: stage I chronic lymphocytic leukemia; cancer survivor; childhood acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; juvenile myelomonocytic leukemia; childhood chronic myelogenous leukemia; metabolic syndrome; long-term effects secondary to cancer therapy in children; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; cardiovascular complications
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Neoplasms by Histologic Type; Neoplasms; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Leukemia; Metabolic Syndrome
• Other Study ID Numbers: IR 7141; P30CA077598 (U.S. NIH Grant/Contract); UMN-2003NT063; CDR0000642276 (Registry Identifier: NCI); IR-6980 (Other Identifier: Former FHCRC IRB ID); FHCRC-2357.00 (Other Identifier: Former FHCRC ID)