Metabolic Syndrome in Adult Survivors of Childhood ALL

儿童期急性淋巴细胞白血病成年幸存者的代谢综合征

• 批准号: 7104728
• 负责人: James G Gurney
• 金额: $ 16.29万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7104728
• 关键词: acute lymphocytic leukemia; cardiovascular disorder; case history; clinical research; combination cancer therapy; diabetes mellitus; disease /disorder etiology; disease /disorder proneness /risk; endocrine disorder; head; health behavior; human middle age (35-64); human subject; long term survivor; longitudinal human study; metabolism disorder; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; obesity; patient oriented research; radiation therapy dosage; skull; somatotropin; therapy adverse effect; vascular endothelium; young adult human (21-34)

DESCRIPTION (provided by applicant): Treatment for acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, involves 24 to 36 months of chemotherapy and high dose steroids. Additionally, cranial radiation is sometimes included for treatment or prevention of central nervous system involvement. The 5-year survival probability of childhood is all over 80%, and there are tens of thousands of adult survivors worldwide. These individuals have a higher than expected frequency of obesity and early mortality from cardiovascular disease. Childhood ALL survivors may also be at increased risk for the metabolic syndrome, a constellation of disorders characterized by central obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension. The syndrome is clearly associated with substantially elevated risks for type 2 diabetes mellitus and atherosclerotic coronary disease. Deficiency in growth hormone secretion, which can result from damage to the hypothalamic-pituitary axis from either chemotherapy or cranial radiation, has been implicated in the pathogenesis of metabolic syndrome in childhood cancer survivors. 75 adult survivors of childhood ALL, ages 18-49 years will be randomly selected and recruited from an ongoing epidemiologic study to participate in a 2-day clinical evaluation. The aims of this study are to: 1) compare the extent to which prevalence of the metabolic syndrome is higher in ALL survivors than in same age, same sex population norms; 2) evaluate the relation between growth hormone deficiency and the metabolic syndrome; 3) investigate whether endothelial impairment and other early signs of cardiovascular disease are more prevalent among ALL survivors with, versus without, the metabolic syndrome; and 4) compare whether adjuvant cranial radiation increases risk for the metabolic syndrome above that of chemotherapy alone. A comparative evaluation of health behaviors and health knowledge related to diabetes, cardiovascular disease, physical activity, and nutrition, and will also be included in the study. This proposal addresses the great need for clinical research on long-term, adverse effects of childhood cancer and its treatment, particularly those that are preventable or modifiable. The study will provide important data on potential etiologic factors, such as growth hormone deficiency and cranial radiation, and on potential avenues for education and intervention, such as targeted modifications of physical activity and dietary habits.

描述（由申请人提供）： 急性淋巴细胞白血病（所有）是最常见的儿童期恶性肿瘤，涉及24至36个月的化学疗法和高剂量类固醇。另外，有时包括用于治疗或预防中枢神经系统参与的颅辐射。童年的5年生存概率均超过80％，全世界有成千上万的成人幸存者。这些人的肥胖症频率高于心血管疾病的预期频率和早期死亡率。儿童时期所有幸存者也可能有代谢综合征的风险增加，这是一个以中枢肥胖，胰岛素抵抗，葡萄糖不耐症，血脂异常和高血压为特征的疾病星座。该综合征显然与2型糖尿病和动脉粥样硬化冠状动脉疾病的风险显着升高有关。生长激素分泌缺乏，这可能是由于化学疗法或颅放射的下丘脑 - 垂体轴的损害，与儿童癌症幸存者的代谢综合征的发病机理有关。 75名童年成年幸存者，所有年龄在18-49岁之间的幸存者将被随机选择并从正在进行的流行病学研究中招募，以参加为期2天的临床评估。这项研究的目的是：1）比较所有幸存者的代谢综合征的患病率的程度高于同一年龄，同一性别人群规范的程度； 2）评估生长激素缺乏症与代谢综合征之间的关系； 3）研究内皮障碍和心血管疾病的其他早期迹象是否在所有幸存者中更为普遍，而没有代谢综合征。 4）比较辅助颅辐射是否会增加代谢综合征的风险，而不是化学疗法的风险。对与糖尿病，心血管疾病，体育锻炼和营养有关的健康行为和健康知识的比较评估，并将包括在研究中。该建议旨在解决有关儿童癌症及其治疗的长期，不良影响的临床研究的巨大需求，尤其是那些可预防或可修改的治疗方法。该研究将提供有关潜在病因因素的重要数据，例如生长激素缺乏症和颅辐射，以及潜在的教育和干预途径，例如针对性的体育锻炼和饮食习惯。