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.

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