Metabolic Syndrome Following Transplant for Leukemia

白血病移植后的代谢综合征

• 批准号: 7937785
• 负责人: KEVIN S BAKER
• 金额: $ 48.61万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937785
• 关键词: Acute leukemia; Address; Adolescent; Adult; Adverse effects; Age; Allogenic; Autologous; Behavioral; Blood Pressure; Blood Vessels; Body mass index; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cell Transplants; Central obesity; Child; Childhood; Cholesterol; Chronic; Clinical; Controlled Study; Cranial Irradiation; Data; Development; Diet; Dietary intake; Disease; Dose; Dyslipidemias; Electromagnetic Energy; Exposure to; Fasting; Frequencies; Funding; Gender; Glucocorticoids; Glucose; Glucose Intolerance; Growth; Hematologic Neoplasms; Hematopoietic; High Dose Chemotherapy; Hypertension; Impairment; Incidence; Individual; Inflammation Mediators; Inflammatory; Insulin; Insulin Resistance; Interleukin-6; Intervention; Late Effects; Length; Leptin; Lipids; Malignant - descriptor; Malignant Childhood Neoplasm; Measurement; Measures; Mediating; Mentored Patient-Oriented Research Career Development Award; Metabolic syndrome; Modality; Neuraxis; Non-Insulin-Dependent Diabetes Mellitus; Non-Malignant; Obesity; Participant; Pattern; Pharmacotherapy; Physical activity; Prevention; Proteins; Radiation; Regimen; Research; Research Personnel; Risk; Risk Factors; Scanning; Serum; Survivors; Therapeutic; Thick; Time; Transplantation; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Vasodilation; Whole-Body Irradiation; active control; adipokines; adiponectin; cancer therapy; cardiovascular risk factor; chemotherapy; cytokine; design; follow-up; graft vs host disease; growth hormone deficiency; intima media; leukemia; low density lipoprotein triglyceride; mortality; normal aging; premature; programs; sex; young adult

DESCRIPTION (provided by applicant): Adult survivors of acute leukemia in childhood have a higher than expected frequency of obesity early mortality from cardiovascular disease, and an increased risk for the metabolic syndrome (MS), and this may be more common in individuals who received hematopoietic cell transplant (HCT) as part of their therapy. The major objective of this research is to evaluate the relationship between HCT specific treatment exposures and the development of insulin resistance and the MS in adolescent and young adult survivors after HCT for treatment of hematologic malignancies in childhood, and this application is the result of the successful progression of Dr. Baker's recent K23 award, funded to study late effects in survivors after HCT. The specific aims of this proposal are: 1) to measure insulin resistance (IR, euglycemic insulin clamp) serum insulin, glucose, and lipids; to obtain blood pressure, and anthropometric measurements; and DEXA scans in 190 survivors of HCT and 190 controls; 2) evaluate the association of specific HCT treatments exposures with the development of the MS; 3) to measure cytokines, CRP and adipokines; 4) to measure early signs of impaired endothelial function and sub-clinical cardiovascular disease; and 5) to obtain measures of dietary intake and physical activity in HCT survivors and controls. These data will address the hypotheses that a) HCT survivors will be more IR, and that IR will increase independent of age with longer follow-up after HCT, b) specific HCT treatment exposures will be associated with growth hormone deficiency and higher degrees of IR, c) allogeneic HCT will be associated with higher levels of inflammatory mediators associated with IR, d) vascular measurements of sub-clinical cardiovascular changes will be higher in survivors with MS and will be associated with total body irradiation exposure (TBI), e) HCT survivors will be less physically active and this will be correlated with exposure to TBI and with having had graft vs. host disease. This research offers a significant and exciting opportunity to explore a potentially modifiable late effect of childhood cancer treatment, the MS and the associated heightened risk for premature cardiovascular disease and type 2 diabetes. Since HCT is a widely applied therapeutic modality for leukemia as well as many other malignant and non-malignant diseases in children and adults with thousands of individuals worldwide every year becoming survivors, it is an increasingly important group to study.

描述（由申请人提供）：儿童急性白血病的成年幸存者比心血管疾病早期死亡的肥胖早期死亡率高于预期的，并且代谢综合征（MS）的风险增加，这在接受的个体中可能更常见造血细胞移植（HCT）作为其治疗的一部分。这项研究的主要目的是评估HCT特异性治疗暴露与HCT后青少年和年轻成人幸存者中胰岛素抵抗和MS的发展之间的关系，以治疗儿童时期血液学恶性肿瘤，而这一应用是成功的结果。 Baker博士最近的K23奖的进展，资助用于研究HCT后幸存者的后期影响。该提案的具体目的是：1）测量胰岛素抵抗（IR，尿糖胰岛素夹）血清胰岛素，葡萄糖和脂质；获得血压和人体测量； Dexa扫描了190名HCT幸存者和190个对照； 2）评估特定的HCT治疗暴露与MS的发展的关联； 3）测量细胞因子，CRP和脂肪因子； 4）测量内皮功能受损和临床下心血管疾病的早期迹象； 5）获得HCT幸存者和对照组中饮食摄入和体育活动的度量。这些数据将解决以下假设：a）HCT幸存者将更加IR，并且IR将在HCT之后随着年龄而独立于年龄增加，b）特定的HCT治疗暴露将与生长激素缺乏症和IR较高程度有关，c）同种异体HCT将与与IR相关的较高水平的炎症介质有关，D）MS的幸存者的血管测量值将更高，并且与全身辐照暴露（TBI）相关，E） HCT幸存者的身体活动较低，这将与暴露于TBI以及患有移植物与宿主疾病有关。这项研究为探索儿童癌症治疗，MS以及相关的高端心血管疾病和2型糖尿病的风险增加的可能改变的晚期效应提供了一个巨大而激动人心的机会。由于HCT是白血病的一种广泛应用的治疗方式，以及每年在全球成千上万个个人的儿童和成人中，许多其他恶性疾病和非恶性疾病成为幸存者，因此这是一个越来越重要的群体。

项目成果

Bone mineral density in children with fanconi anemia after hematopoietic cell transplantation.

范可尼贫血儿童造血细胞移植后的骨密度。

• DOI: 10.1016/j.bbmt.2015.01.002
• 发表时间: 2015
• 期刊: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
• 作者: Petryk,Anna;Polgreen,LyndaE;Barnum,JessieL;Zhang,Lei;Hodges,JamesS;Baker,KScott;Wagner,JohnE;Steinberger,Julia;MacMillan,MargaretL
• 通讯作者: MacMillan,MargaretL

The role of FSH in body composition in hematopoietic cell transplant recipients.

FSH 在造血细胞移植受者身体成分中的作用。

• DOI: 10.1111/petr.14130
• 发表时间: 2022
• 期刊: Pediatric transplantation
• 影响因子: 1.3
• 作者: Roelofs,EricaJ;Dengel,DonaldR;Wang,Qi;Hodges,JamesS;Steinberger,Julia;Baker,Scott
• 通讯作者: Baker,Scott