Anthraycline-related cardiotoxicity in long-term survivors of lymphoma

淋巴瘤长期幸存者与蒽环类药物相关的心脏毒性

基本信息

批准号：
8569676
负责人：
Saro Armenian
金额：
$ 19万
依托单位：
BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8569676
关键词：
Address Adult Adult Lymphoma Age Anthracyclines Autologous Behavior Biological Markers Blood Cancer Survivor Cardiac Cardiotoxicity Cardiovascular system Chest Collagen Congestive Heart Failure Cross-Sectional Studies Cyclophosphamide Deceleration Demographic Factors Detection Deterioration Development Diagnosis Disease Dose EFRAC Early Diagnosis Early identification Echocardiography Functional disorder Galectin 3 General Population Health High Dose Chemotherapy High Prevalence Hodgkin Disease Image Incidence Individual Injury Intervention Journals Lead Left Left Ventricular Dysfunction Left Ventricular Ejection Fraction Left Ventricular Function Length Life Style Lipids Long-Term Survivors Lymphoma Measurement Measures Morbidity - disease rate Myocardial Natriuretic Peptides New England Non-Hodgkin&apos s Lymphoma Oncologist Pathway interactions Patients Performance Population Populations at Risk Prevalence Process Radiation Recommendation Relaxation Renin-Angiotensin System Research Design Rest Risk Role Shortening Fraction Staging Stress Survivors Therapeutic Time Tissues Troponin Two-Dimensional Echocardiography Ventricular Ventricular Remodeling Vertebral column Whole-Body Irradiation cardiovascular risk factor chemotherapy childhood cancer survivor cohort conditioning effective intervention follow-up functional disability glucose metabolism hematopoietic cell transplantation high risk indexing innovation metabolomics mortality novel oncology outcome forecast oxidation prevent public health relevance screening sex

项目摘要

DESCRIPTION (provided by applicant): Anthracyclines form the backbone of therapy for lymphoma (Hodgkin [HL] and non-Hodgkin lymphoma [NHL]). However, the use of anthracyclines is limited by a dose-dependent association between anthracyclines and risk of cardiotoxicity that can lead to congestive heart failure (CHF). Lymphoma survivors are at a 2- to 5-fold increased risk of developing CHF when compared with the general population; autologous hematopoietic cell transplantation (HCT) survivors have an especially high risk. The overall prognosis is poor - five-year survival is less than 50% after CHF diagnosis. Anthracycline-induced CHF is a progressive disorder, with a period of asymptomatic left ventricular (LV) dysfunction characterized by dilation of the LV chamber, thinning of the myocardial wall, and increase in LV end-systolic wall stress (ESWS), a well-established precursor that precedes other indices of systolic function (LV ejection fraction [EF] and shortening fraction [SF]). Traditionally, detection of anthracycline-related LV dysfunction has relied upon echocardiographic screening using resting EF and SF. However, these parameters represent late-occurring changes in myocardial function. By the time decline in EF and SF are detected, functional deterioration is essentially irreversible, emphasizing the need for biomarkers that would facilitate identification of cardiac damage at an earlier stage, such that effective interventions can halt or reverse the process and prevent development of overt CHF. We have recently completed a study describing sensitive echocardiographic indices and blood biomarkers in childhood cancer survivors, and are now conducting a pharmacologic intervention to reverse myocardial remodeling in childhood cancer survivors at high risk for CHF. In the proposed study, we aim to address these gaps in anthracycline- exposed adults with lymphoma. Using a cross-sectional study design, this proposal will examine the role of novel echocardiographic (Tissue Doppler imaging, myocardial deformation [speckle tracking echocardiography], 2D- M-mode derived diastolic and systolic indices) and blood (cardiac troponins, natriuretic peptides, Galectin-3, ST-2, metabolomics) indices in detecting LV dysfunction (abnormal ESWS) in adult lymphoma survivors treated with anthracyclines. We will also measure these indices in age- and sex-matched healthy controls, in order to define the range for non-anthracycline-exposed individuals, and use these values to describe the magnitude of abnormality in the anthracycline-exposed lymphoma survivors. The current study's innovation lies in its ability to leverage existing information from childhood cancer survivors and non- oncology populations to develop a comprehensive assessment of cardiac function in adults with lymphoma. Information obtained from this study may be used to develop more comprehensive screening strategies in at risk populations, and to use these intermediate endpoints for pharmacologic interventions aimed at preventing CHF in survivors with early LV dysfunction.

描述（由申请人提供）：蒽环类动物形成淋巴瘤治疗的骨干（Hodgkin [HL]和非霍奇金淋巴瘤[NHL]）。然而，蒽环类药物的使用受到邻苯二甲酸盐和心脏毒性风险之间的剂量依赖性关联的限制，这可能导致充血性心力衰竭（CHF）。与普通人群相比，淋巴瘤幸存者的发展CHF风险增加了2至5倍。自体造血细胞移植（HCT）幸存者的风险特别高。总体预后较差 - 二线诊断后的五年生存率小于50％。 Anthracycline-induced CHF is a progressive disorder, with a period of asymptomatic left ventricular (LV) dysfunction characterized by dilation of the LV chamber, thinning of the myocardial wall, and increase in LV end-systolic wall stress (ESWS), a well-established precursor that precedes other indices of systolic function (LV ejection fraction [EF] and shortening fraction [SF]).传统上，使用静止EF和SF检测与蒽环类相关的LV功能障碍的检测依赖于超声心动图筛选。但是，这些参数代表心肌功能的晚期变化。到检测到EF和SF的下降时，功能恶化本质上是不可逆的，强调了对生物标志物的需求，该生物标志物将促进早期阶段鉴定心脏损伤，因此有效的干预措施可以停止或逆转过程并防止其发展公开CHF。我们最近完成了一项研究，描述了儿童癌症幸存者中敏感的超声心动图指数和血液生物标志物，现在正在进行一项药理干预措施，以逆转儿童期癌症幸存者的心肌重塑，处于CHF高风险。在拟议的研究中，我们旨在解决蒽环类暴露的淋巴瘤成年人中的这些差距。使用横截面研究设计，该建议将研究新型超声心动图（组织多普勒成像，心肌变形[斑点跟踪超声心动图]，2D-M模式衍生的舒张性舒张期和收缩性疾病）和血液（心脏曲霉蛋白，Natriuretic Peptides，natriuretic Peptides，galectin-lv），ST-2-MENT-ST-2-MENT-ST-2-M-MODE，St.蒽环类药物治疗的成年淋巴瘤幸存者中功能障碍（异常ESW）。我们还将在年龄和性别匹配的健康对照中衡量这些指数，以定义非邻国暴露的个体的范围，并使用这些值来描述邻苯二胺暴露的淋巴瘤幸存者中异常的幅度。当前的研究的创新在于它有能力利用儿童癌症幸存者的现有信息和非肿瘤学人群以对淋巴瘤成人心脏功能进行全面评估。从这项研究中获得的信息可用于制定风险种群中更全面的筛查策略，并使用这些中间端点进行药物干预措施，以防止具有早期LV功能障碍的幸存者中的CHF。