Aging trajectories and outcomes of older adults with acute myeloid leukemia

患有急性髓性白血病的老年人的衰老轨迹和结果

• 批准号: 10735257
• 负责人: Vijaya Raj Bhatt
• 金额: $ 61.07万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-12 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10735257
• 关键词: Activities of Daily Living; Acute Myelocytic Leukemia; Adult; Aftercare; Age; Aging; Attention; Auditory; BCL-2 Protein; Brain; Cognition; Cognitive; Cognitive aging; Data; Decision Making; Diagnosis; Disease; Disease remission; Dorsal; Education; Elderly; Electroencephalography; Enrollment; European Organization for Research and Treatment of Cancer; Event; Exercise; Goals; Hematologic Neoplasms; Impaired cognition; Impairment; Interdisciplinary Study; Knowledge; Longitudinal cohort study; Measures; Methods; Neuropsychological Tests; Neurosciences; Newly Diagnosed; Oncologist; Outcome; Participant; Patients; Physical Function; Quality of life; Questionnaires; Recommendation; Research; Risk; Risk Factors; Scientist; Short-Term Memory; Time; Visual; attentional control; cancer therapy; chemotherapy; cognitive function; cognitive process; cognitive reserve; comorbidity; comparison control; distraction; executive function; frailty; functional decline; functional improvement; functional independence; health related quality of life; improved; insight; instrumental activity of daily living; leukemia; leukemia treatment; multiple chronic conditions; neuroprotection; novel; novel strategies; novel therapeutic intervention; sex; shared decision making; success

PROJECT SUMMARY In the US, over one-third of older adults ≥60 years with acute myeloid leukemia (AML) die without receiving any chemotherapy, primarily due to concerns of cognitive decline and loss of functional independence if they chose to undergo intensive chemotherapy. A combination of venetoclax and low-intensity chemotherapy offers an effective new treatment for AML. However, several knowledge gaps exist about this new approach. Venetoclax targets neuroprotective B-cell lymphoma 2 (Bcl-2) proteins, but the actual risk of cognitive decline and loss of functional independence following its use, and the factors that increase such risks, are still unclear. Our preliminary data demonstrated that many older adults with AML had stable or improved cognitive and physical function, functional independence, and health-related quality of life (HRQOL) from the time of diagnosis to three months following newer treatments. These novel findings highlight the success of newer treatments in improving cognitive function, functional independence, and HRQOL. Despite this, frailty and multimorbidity were identified as risk factors for functional decline. We also utilized the NCI-recommended neuroscience approach and conducted electroencephalography (EEG)/event-related brain potential (ERP) studies. In our study, adults with hematological cancers versus healthy adults demonstrated altered activity in the dorsal attention and central executive brain networks prior to treatment. Confirmation of these findings will identify the risk of a decline in attention and executive function, functional independence, and HRQOL, and will provide novel mechanistic insights into the activity of brain networks in older adults with AML. In the proposed longitudinal cohort study, we will enroll older adults with a new diagnosis of AML who will receive venetoclax-based treatments, and age-, sex-, and education-matched non-cancer controls. We will compare the two groups on the following outcomes: attention and executive function (Trail Making and other neuropsychological tests), functional independence, HRQOL, and EEG/ERP measures (ERP studies during auditory-visual distraction tasks to measure brain activity) at enrollment and over 12 months. The study aims are: Aim 1. Determine the longitudinal attention and executive function of older adults with AML before and after venetoclax-based treatment, as compared to age-, sex-, and education-matched non-cancer controls. Aim 2. Determine longitudinal changes in functional independence and HRQOL in older adults with AML versus controls, and examine their associations with longitudinal changes in attention and executive function. Aim 3. Measure longitudinal changes in the activity of brain networks of older adults with AML before and after venetoclax-based treatment, as compared to controls. This is the first study to apply rigorous methods to overcome key limitations of prior studies and to advance the current limited cognitive aging research in patients with AML. Understanding factors associated with stable/improved functional trajectory following new treatment can change treatment paradigms and is essential to inform critical decision-making of older adults with AML considering chemotherapy for this fatal disease. The goals align with the NCI/NIA priorities.

项目摘要 在美国，超过三分之一的老年人≥60岁，急性髓细胞性白血病（AML）死亡，没有收到任何 化学疗法，主要是由于对认知能力下降和功能独立丧失的关注 接受强化化疗。 Venetoclax和低强度化疗的结合提供了 有效的AML新疗法。但是，关于这种新方法存在一些知识差距。 Venetoclax 靶向神经保护性B细胞淋巴瘤2（BCL-2）蛋白，但实际上认知下降和丧失的风险 使用后的功能独立性以及增加此类风险的因素仍不清楚。我们的 初步数据表明，许多患有AML的老年人具有稳定或改善的认知和身体 功能，功能独立性和与健康相关的生活质量（HRQOL）从诊断到三个 较新的治疗后几个月。这些新颖的发现突出了新疗法在改善方面的成功 认知功能，功能独立性和HRQOL。尽管如此，确定了脆弱和多种病的 作为功​​能下降的风险因素。我们还利用了NCI征载的神经科学方法和 进行了脑电图（EEG）/事件相关的大脑电位（ERP）研究。在我们的研究中，成年人 血液学癌症与健康成年人表现出在背注意和中心的活性改变 治疗前执行大脑网络。确认这些发现将确定下降的风险 注意力和执行功能，功能独立性和HRQOL，并将提供新颖的机械 对AML老年人的大脑网络活动的洞察力。在拟议的纵向队列研究中，我们 将招募老年人接受AML的新诊断，他们将接受基于Venetoclax的治疗方法，以及年龄， 性别和教育匹配的非癌症控制。我们将在以下结果中比较这两个小组： 注意力和执行功能（Trail和其他神经心理学测试），功能独立性， HRQOL和EEG/ERP测量（在听觉 - 视觉分心任务中的ERP研究以测量大脑活动） 入学率和超过12个月。研究目的是：目标1。确定纵向关注和执行 与年龄，性别和年龄，性别相比 教育匹配的非癌症控制。目标2。确定功能独立性的纵向变化和 AML与对照组的老年人中的HRQOL，并检查其与纵向变化的关联 注意和执行功能。目标3。测量较老的大脑网络活动的纵向变化 与对照组相比，基于Venetoclax的治疗前后患有AML的成年人。这是第一个研究 采用严格的方法来克服先前研究的关键局限性并提高当前有限的认知能力 AML患者的衰老研究。了解与稳定/改进功能轨迹相关的因素 遵循新的治疗可以改变治疗范例，对于为关键决策提供了至关重要的 患有AML的老年人正在考虑这种致命疾病的化学疗法。目标与NCI/NIA优先级保持一致。

项目成果

Determining treatment tolerance and fitness for intensive chemotherapy in older adults with AML: a call to action.

确定患有 AML 的老年人对强化化疗的治疗耐受性和适应性：行动呼吁。

• DOI: 10.1182/blood.2023022611
• 发表时间: 2024
• 期刊: Blood
• 影响因子: 20.3
• 作者: Bhatt,VijayaRaj;Uy,GeoffreyL;Klepin,HeidiD
• 通讯作者: Klepin,HeidiD

Diet and Nutritional Supplementation in Patients With Cancer: Is More Necessarily Better?

癌症患者的饮食和营养补充：越多越好吗？

• DOI: 10.1200/op.23.00746
• 发表时间: 2024
• 期刊: JCO oncology practice
• 影响因子: 4
• 作者: Dhakal,Prajwal;Bhatt,VijayaRaj
• 通讯作者: Bhatt,VijayaRaj