Chronic Health Conditions in Survivors of Down Syndrome-Associated Leukemia

唐氏综合症相关白血病幸存者的慢性健康状况

基本信息

批准号：
10650348
负责人：
Maria Monica Gramatges
金额：
$ 58.86万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-20 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10650348
关键词：
Acute Acute Lymphocytic Leukemia Acute Myelocytic Leukemia Acute leukemia Address Age Age of Onset Area Attention Biological Biology Cancer Survivorship Caring Case Series Cataract Cerebrovascular Disorders Child Child Support Childhood Acute Myeloid Leukemia Chromosome 21 Chronic Clinical Clinical Practice Guideline Clinical assessments Cohort Studies Collaborations Congenital Abnormality Congenital Heart Defects Constitution Constitutional Coronary Arteriosclerosis Data Dementia Developmental Disabilities Disparity Down Syndrome Epilepsy Ethnic Origin Etiology Exclusion Frequencies General Population Genetic Genetic Diseases Guidelines Hair Health Health Status Hearing problem Incidence Individual Knowledge Late Effects Length Life Longterm Follow-up Malignant Neoplasms Medical Records Methods Neurocognitive Neuropsychology Osteopenia Outcome Parents Participant Pediatric Oncology Group Persons Phenotype Population Populations at Risk Premature Menopause Prevalence Proxy Quality of life Race Recording of previous events Refractive Errors Registries Reporting Research Risk Risk Factors Severities Site Skin Wrinkling Socioeconomic Factors Structural Congenital Anomalies Subgroup Surveys Survivors Susceptibility Gene Testing Thyroid Diseases Treatment outcome Treatment-related toxicity Trisomy Visual Vulnerable Populations Work adverse outcome cancer diagnosis cancer epidemiology cancer therapy childhood cancer survivor cohort executive function experience functional disability genetic association health disparity health related quality of life high risk population improved leukemia leukemia treatment multidisciplinary outcome disparities peer polygenic risk score processing speed prospective recruit research study sex sociodemographic factors survivorship telomere

项目摘要

SUMMARY Down syndrome (DS) is a genetic disorder characterized by a constitutional trisomy of chromosome 21, neurocognitive delay, phenotypic features, co-occurring structural birth defects, and an increased risk for chronic health conditions (CHC) such as thyroid disease, osteopenia, seizure disorder, and visual/hearing problems. Children with DS have a 10-20 fold excess risk for acute leukemia (AL) compared with the general population, and are also at significantly greater risk for acute therapy-related toxicities. However, few studies have reported late effects of cancer therapy in survivors of DS-AL, and none have investigated whether these CHC differ from those experienced by children with DS and no history of cancer. Therefore, although a higher than expected incidence of late effects is reported in DS-AL survivors, the prevalence and severity of these CHC relative to the CHC associated with DS is unknown. Further, AL treatment confers well-described risks for deficits in attention, processing speed, and executive function, but only one small case series has investigated neuro-psychological (NP) outcomes in DS-AL survivors. Due to a systematic exclusion from research based on their differing baseline health status, DS-AL survivors are an at-risk population that is largely unstudied. To address this critical knowledge gap, we will characterize late effects experienced by DS-AL childhood cancer survivors by determining the prevalence and severity of CHC and clinical and NP outcomes in DS-AL survivors. Recruiting from DS participants in Children’s Oncology Group studies and registries, our methods include both medical record data abstraction and prospective in-person and survey-based assessments. Aim 1 will establish an annotated and comprehensively-characterized, contemporary cohort of DS-AL survivors. Aim 2 will leverage access to a well-established cohort of DS persons without cancer history to compare CHC and NP outcomes with those observed in DS-AL survivors. Aim 3 will identify clinical, genetic, and biological risk determinants of late effects in DS-AL survivors. Based on our strong preliminary data, we hypothesize that the prevalence and severity of specific CHC and adverse clinical and NP outcomes will exceed those observed in non-DS AL and in matched DS controls without cancer history. Further, we expect that DS ALL susceptibility loci will extend to association with risk for CHC, and correspond with incidence of co-occurring birth defects. Last, we anticipate that shorter telomere length is associated with adverse NP outcomes. Our multi-disciplinary team has a strong history of collaboration and expertise in leukemia and cancer survivorship (Gramatges), DS- AL (Rabin), epidemiology of cancer and birth defects (Lupo), DS-associated CHC (Rosser), NP outcomes in DS survivors (Jacola), and CHC in survivors of childhood cancer (Chow). With the support of the Children’s Oncology Group, this multi-site, national study will characterize cancer treatment outcomes in DS-AL survivors. We anticipate our results will improve survivorship care by informing clinical practice guidelines for DS-AL survivors, mitigating outcome disparities in this vulnerable population.

概括唐氏综合症 (DS) 是一种遗传性疾病，其特征是 21 号染色体存在三体性，神经认知延迟、表型特征、同时发生的结构性出生缺陷以及增加的风险慢性健康状况 (CHC)，例如甲状腺疾病、骨质减少、癫痫症和视力/听力障碍与一般儿童相比，患有 DS 的儿童患急性白血病 (AL) 的风险高出 10-20 倍。人群，并且发生急性治疗相关毒性的风险也明显更高。然而，很少有研究。已经报告了癌症治疗对 DS-AL 幸存者的晚期影响，但没有人调查这些是否 CHC 不同于患有 DS 且无癌症病史的儿童所经历的情况，尽管其程度较高。据报道，DS-AL 幸存者中迟发效应的发生率高于预期，这些效应的发生率和严重程度 CHC 相对于 DS 相关的 CHC 尚不清楚。此外，AL 治疗带来的风险已得到充分描述。注意力、处理速度和执行功能方面的缺陷，但仅研究了一个小型案例系列 DS-AL 幸存者的神经心理 (NP) 结果由于基于研究的系统性排除。 DS-AL 幸存者的基线健康状况不同，属于高危人群，但很大程度上尚未得到研究。为了解决这一关键的知识差距，我们将描述 DS-AL 童年经历的后期影响通过确定 CHC 的患病率和严重程度以及 DS-AL 的临床和 NP 结局来评估癌症幸存者从儿童肿瘤学小组研究和登记中招募 DS 参与者，我们的方法。目标 1 包括医疗记录数据提取以及前瞻性的现场评估和基于调查的评估。将建立一个有注释且具有全面特征的当代 DS-AL 幸存者群体。 2 将利用对没有癌症病史的完善 DS 人群的访问来比较 CHC 和目标 3 将通过在 DS-AL 幸存者中观察到的 NP 结果来确定临床、遗传和生物学风险。 DS-AL 幸存者后期影响的决定因素根据我们强有力的初步数据，我们发现特定 CHC 的患病率和严重程度以及不良临床和 NP 结局将超过在此外，我们预计 DS ALL 易感性。基因座将延伸至与 CHC 风险的关联，并与同时发生的出生缺陷的发生率相对应。最后，我们预计较短的端粒长度与不利的 NP 结果相关。团队在白血病和癌症生存 (Gramatges)、DS- AL (Rabin)、癌症和出生缺陷流行病学 (Lupo)、DS 相关 CHC (Rosser)、NP 结局 DS 幸存者 (Jacola)，以及儿童癌症幸存者的 CHC (Chow)。在儿童肿瘤学小组的支持下，这项多地点全国性研究将描述癌症的特征我们预计我们的结果将通过告知改善幸存者护理。 DS-AL 幸存者的临床实践指南，减少这一弱势群体的结果差异。