Treatment-Related Cardiotoxicity in Children with Relapsed Acute Myeloid Leukemia - Natural History, Occurrence and Implications

复发性急性髓系白血病儿童的治疗相关心脏毒性 - 自然史、发生情况和影响

• 批准号: 10663387
• 负责人: Kelly Diringer Getz
• 金额: $ 74.68万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10663387
• 关键词: Acute Myelocytic Leukemia; Address; Adolescent; Cardiomyopathies; Cardiotoxicity; Chemotherapy-Oncologic Procedure; Child; Childhood; Childhood Acute Myeloid Leukemia; Clinical Trials Cooperative Group; Clinical Trials Database; Computerized Medical Record; Data; Diagnosis; Disease; Disease remission; Disease-Free Survival; Echocardiography; Effectiveness; Electronic Health Record; Evaluation; Functional disorder; Goals; Health Information System; Heart failure; Impact evaluation; Incidence; Injury; Institution; Knowledge; Left; Left Ventricular Function; Long Term Survivorship; Malignant Childhood Neoplasm; Malignant Neoplasms; Measures; Mediating; Mediator; Morbidity - disease rate; Muscle Cells; Myocardial dysfunction; Natural History; Outcome; Patients; Pediatric Oncology Group; Phenotype; Probability; Prognosis; Recovery; Recurrent disease; Refractory; Refractory Disease; Regimen; Relapse; Risk; Salvage Therapy; Selection for Treatments; Source; Standardization; Stem cell transplant; Supportive care; Survivors; Time; Toxic effect; Transplantation; Treatment outcome; Variant; Ventricular; Work; adverse outcome; chemotherapy; clinical development; cohort; conditioning; data resource; experience; follow-up; functional decline; graft vs host disease; heart function; improved; improved outcome; leukemia treatment; mortality; prevent; standard of care; survival outcome; treatment effect; treatment risk; treatment trial

Project Summary/Abstract Acute myeloid leukemia (AML) is the second most common malignancy among children and adolescents. The prognosis of pediatric AML has improved significantly over recent decades, but still nearly half of patients suffer refractory disease or relapse following a first remission. These patients have a relatively poor prognosis, with a probability of five-year survival following relapse of only ~35%. This is achieved with intensive chemotherapy leading to potentially significant toxicity and even treatment-related mortality. While there has been substantial standardization in practice related to frontline therapy for AML, there is greater variability in treatment of relapsed disease – variability that is poorly understood. Furthermore, given the variability in treatment and the small numbers of patients at any one institution, there is a dearth of information on toxicity risks for the treatments being utilized for refractory or relapsed disease. Cardiotoxicity is a prevalent adverse consequence of AML therapy. However, given the incomplete data captured by frontline clinical trial databases once a patient experiences relapse, data on the onset, progression and potential recovery of cardiotoxicity are generally restricted to the time period during and shortly after frontline therapy and late in long-term survivorship. The current lack of data over the duration of the patient experience precludes a complete assessment of the incremental risks associated with AML therapy, including transplant and salvage. Data on how early cardiotoxicity onset during frontline therapy may impact approach to treatment for relapsed disease, the impact of salvage therapies on cardiac function, and subsequent survival outcomes is thus, also poorly understood. The aims of the proposed work are to establish a unique data resource by combining data from the Children's Oncology Group (COG) clinical trial databases, electronic medical record (EMR) abstraction for a multi-center AML cohort, longitudinal quantitative echocardiographic measures of measures of left ventricular (LV) size, systolic and diastolic function, and administrative data from the Pediatric Health Information System, that will enable assessments comparing toxicity and outcomes associated with the variety of approaches to therapy for refractory/relapsed AML. Specifically, our aims include the following: (1) determine the natural history cardiotoxicity and the incremental effects of treatment from initial diagnosis, through relapse and early post-relapse follow-up, (2) to quantify the influence of prevalent salvage therapies on longitudinal changes in LV size, systolic and diastolic function and the incidence of cardiomyopathy, and (3) to evaluate salvage chemotherapy and transplant as mediators of the documented association between early cardiotoxicity onset during frontline therapy and decreased overall survival.

项目摘要/摘要 急性髓样白血病（AML）是儿童和青少年中第二大常见的恶性肿瘤。 在近几十年来 首次缓解后会遭受难治性疾病或缓解。这些患者的预后相对较差， 仅减轻约35％后，五年生存的概率。这是通过密集的 化学疗法导致潜在的显着毒性，甚至与治疗相关的死亡率。那里有 在与AML的一线治疗有关的实践中是实质性的标准化，差异更大 接力疾病的治疗 - 理解不佳的变异性。此外，考虑到可变性 治疗和任何一个机构的患者数量少，有关毒性的信息死亡 用于难治性或中继疾病的治疗的风险。心脏毒性是一种普遍的不利 AML治疗的结果。但是，鉴于前线临床试验数据库捕获的不完整数据 一旦患者体验继电器，关于发作，进展和潜在恢复心脏毒性的数据是 通常仅限于一线治疗后不久和长期后期的时间段 生存。目前在患者体验期间缺乏数据排除了完整的 评估与AML治疗相关的增量风险，包括移植和打捞。数据上 一线治疗期间的心脏毒性发作如何影响接力疾病的治疗方法， 因此，打捞疗法对心脏功能的影响以及随后的生存结果也很差 理解。拟议工作的目的是通过结合来自的数据来建立独特的数据资源 儿童肿瘤学组（COG）临床试验数据库，电子病历（EMR）抽象 多中心AML队列，纵向定量超声心动图测量左心室的测量值 （LV）大小，收缩和舒张功能以及小儿健康信息系统的管理数据， 这将使评估能够比较与多种方法相关的毒性和结果 耐火/复发AML的治疗。具体来说，我们的目标包括以下内容：（1）确定自然 历史心脏毒性和从初始诊断，通过救济和早期治疗的增量影响 释放后的随访，（2）量化普遍的打捞疗法对纵向变化的影响 LV大小，收缩和舒张功能以及心肌病的事件，（3）评估打捞 化学疗法和移植作为早期心脏毒性发作之间的介体的介体 在一线治疗期间，总体生存率提高。