Risk for Psychopathology and Neurocognitive Impairment in Leukemia Survivors

白血病幸存者的精神病理学和神经认知障碍风险

• 批准号: 8603867
• 负责人: Kevin R Krull
• 金额: $ 49.05万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-05 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8603867
• 关键词: 8 year old; Acute; Acute Lymphocytic Leukemia; Anterior; Anxiety; Area; Attention; Attention deficit hyperactivity disorder; Behavior; Behavior Control; Behavior Therapy; Behavioral; Brain; Brain Injuries; Brain imaging; Cerebrospinal Fluid; Characteristics; Child; Childhood Acute Lymphocytic Leukemia; Childhood Leukemia; Cognitive; Comorbidity; Data; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Enrollment; Evaluation; Executive Dysfunction; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Image; Impairment; Independent Living; Individual; Informal Social Control; Intervention; Late Effects; Leukoencephalopathy; Long Term Survivorship; Long-Term Survivors; Magnetic Resonance Imaging; Maintenance; Measures; Mental Depression; Modeling; Myelin; Neuraxis; Neurocognitive; Newly Diagnosed; Outcome; Parents; Patients; Pattern; Performance; Phase; Phenotype; Population; Predictive Factor; Problem Solving; Problem behavior; Protocols documentation; Psychopathology; Quality of life; Recording of previous events; Recovery; Reporting; Research; Resolution; Risk; Saint Jude Children' s Research Hospital; Sampling; Self Management; Short-Term Memory; Staging; Structure; Survival Rate; Survivors; Symptoms; Thick; Time; Treatment Protocols; base; cell injury; cellular pathology; central nervous system injury; chemotherapy; cingulate cortex; cohort; common treatment; executive function; experience; flexibility; follow-up; frontal lobe; frontal lobe cortex; functional outcomes; improved; leukemia; neurobehavioral; neurotoxicity; performance tests; processing speed; prospective; public health relevance; skills; success; survivorship; therapy design; treatment effect; white matter

DESCRIPTION (provided by applicant): Survival rates for pediatric acute lymphoblastic leukemia (ALL) now exceed 80%. With this growing population of long-term survivors comes recognition that a considerable proportion experience one or more significant late effects. For children undergoing central nervous system (CNS) treatment, common late effects include neurocognitive impairment and neurobehavioral problems. Although these problems first manifest as subtle difficulties with attention and processing speed, they can evolve into deficits in higher order brain functions that significantly impact functional skills in a subset of long-term survivors. Attention and self- regulation are some of the critical foundation skills upon which these higher order brain functions are based (i.e. cognitive flexibility, fluency, working memory, planning, organization, and problem solving abilities). Collectively referred to as "executive functions", these skills are essential for development and maintenance of independent living skills, self-management, and educational and vocational success. Recent research indicates 20-40% of children treated for pediatric ALL experience significant neurocognitive problems. Furthermore, a similar percentage of survivors demonstrate significant symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). We are currently unable to accurately identify patients at greatest risk for these long-term neurocognitive and neurobehavioral impairments. In addition to treatment and intrinsic patient characteristics, potential predictive factors include changes in cognitive or behavioral functioning and brain state during active chemotherapy. Cognitive and behavioral predictive factors include acute changes in attention and self-regulation, which are early manifestations of disrupted executive functions. Brain state factors include evidence of acute neurotoxicity, as expressed through brain imaging. The Total XV protocol at St. Jude Children's Research Hospital (SJCRH) provides a unique opportunity with which to examine the association between early changes in behavior and brain states and later development of executive functions and brain maturation in children who survive pediatric ALL. Between June 2000 and October 2007, 408 ALL patients with newly diagnosed ALL were enrolled and treated at SJCRH on this institutionally-developed protocol using a uniform chemotherapy-only treatment regimen. All children underwent brain magnetic resonance imaging (MRI) during active therapy, as well as cognitive and behavioral evaluations at the same time points. Through this proposal, we plan to utilize existing data collected during acute treatment in the prediction of long-term neurocognitive and brain maturation outcomes. We propose to collect new data on higher order executive functions, symptoms of psychopathology, and structural and functional brain imaging in survivors who are at least 8 years of age and greater than 5 years from diagnosis. The ultimate goal of this effort is to develop a risk model for neurocognitive late-effects in pediatric leukemia, such that early preventative interventions may be targeted to "at-risk" patients.

描述（由申请人提供）：小儿急性淋巴细胞白血病的存活率（所有）现在超过80％。随着长期幸存者人数不断增长，人们认识到，相当大的比例经历了一个或多个重要的后期影响。对于接受中枢神经系统（CNS）治疗的儿童，常见的晚期作用包括神经认知障碍和神经行为问题。尽管这些问题首先表现为随着注意力和处理速度的微妙困难，但它们可以以更高级的大脑功能发展为缺陷，从而在长期幸存者的一部分中显着影响功能技能。注意力和自我调节是这些高级大脑功能所基于的一些关键基础技能（即认知灵活性，流利性，工作记忆，计划，组织和解决问题能力）。这些技能统称为“执行功能”，对于发展和维护独立生活技能，自我管理以及教育和职业成功至关重要。 最近的研究表明，接受儿科治疗的儿童中有20-40％遇到了重大神经认知问题。此外，相似百分比的幸存者表现出注意力缺陷/多动症（ADHD）的显着症状。目前，我们无法准确识别出这些长期神经认知和神经行为障碍的患者。除了治疗和内在的患者特征外，潜在的预测因素还包括在主动化疗期间的认知或行为功能和脑状态的变化。认知和行为预测因素包括注意力和自我调节的急性变化，这是执行功能中断的早期表现。大脑状态因素包括通过大脑成像表达的急性神经毒性的证据。 St. Jude儿童研究医院（SJCRH）的XV总体协议提供了一个独特的机会，可以利用它来检查行为和大脑状态的早期变化与后来的执行功能和大脑成熟的儿童之间的关联。在2000年6月至2007年10月之间，有408名已有新诊断的患者均在SJCRH上纳入并在该机构开发方案中使用统一的纯化疗治疗方案进行了治疗。所有儿童在主动治疗期间均接受了大脑磁共振成像（MRI），以及同时的认知和行为评估。通过该提案，我们计划利用在急性治疗期间收集的现有数据，以预测长期神经认知和大脑成熟结果。我们建议收集有关高级执行功能，心理病理学症状以及至少8岁且诊断出5年以上5年以上的幸存者的结构和功能性脑成像的新数据。这项工作的最终目标是为小儿白血病中神经认知晚期作用开发风险模型，以便早期的预防性干预措施可能针对“处于危险”的患者。

项目成果

Neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on contemporary treatment protocols: A systematic review.

• DOI: 10.1016/j.neubiorev.2015.03.016
• 发表时间: 2015-06
• 期刊: NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
• 影响因子: 8.2
• 作者: Cheung, Yin Ting;Krull, Kevin R.
• 通讯作者: Krull, Kevin R.

Emotional distress in parents of long-term survivors of childhood acute lymphoblastic leukemia.

• DOI: 10.1002/pon.3732
• 发表时间: 2015-09
• 期刊: PSYCHO-ONCOLOGY
• 影响因子: 3.6
• 作者: Malpert, Adele V.;Kimberg, Cara;Luxton, Joshua;Mullins, Larry L.;Pui, Ching-Hon;Hudson, Melissa M.;Krull, Kevin R.;Brinkman, Tara M.
• 通讯作者: Brinkman, Tara M.