BMT Survivor Study-2 (BMTSS-2)

BMT 幸存者研究 2 (BMTSS-2)

基本信息

批准号：
9904585
负责人：
SMITA BHATIA
金额：
$ 156.96万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9904585
关键词：
Address Aftercare Age Aging Alabama Android Behavior Therapy Biological Blood Bone Marrow Transplantation Cause of Death Cessation of life Chemotherapy and/or radiation Chronic Cities Coronary Arteriosclerosis DNA Diabetes Mellitus Diagnosis Eligibility Determination Enrollment Epigenetic Process Frequencies Future General Population Genetic Determinism Genetic Markers Genetic Predisposition to Disease Goals Health Health Insurance Portability and Accountability Act Health behavior Heart failure Hematologic Neoplasms High Prevalence Hospital Costs Hypertension Incidence Individual Infrastructure Intervention Knowledge Life Lymphoma Measures Methodology Minnesota Modality Morbidity - disease rate Multiple Myeloma Neoplasms Online Systems Outcome Pathogenesis Patient Self-Report Patients Peripheral Blood Stem Cell Personal Satisfaction Population Predisposition Premature Mortality Premature aging syndrome Progressive Disease Radiation Recurrence Research Resources Retrospective cohort Risk Sample Size Sampling Site Source Specimen Survivors Technology Testing Therapeutic Time Translational Research Transplant Recipients Transplantation Umbilical Cord Blood Universities Validation Vital Status Work base chemotherapy cohort comorbidity comparison group conditioning conventional therapy demographics design epigenetic marker experience frailty health care service utilization high risk indexing leukemia leukemia/lymphoma mortality premature prevent procedure cost relapse risk repository risk prediction model stem cells transplant survivor treatment risk treatment strategy trend

项目摘要

In 2017, an estimated 1.3 million individuals were living with a hematologic malignancy (HM: leukemia, myeloma or lymphoma) in the US. Frontline use of systemic high-intensity chemotherapy with or without radiation characterizes the management of HM. Patients with progressive disease or at high risk of relapse are treated with even higher intensity chemotherapy/radiation and blood or marrow transplantation (BMT); indeed, BMT is often the only curative option for these patients. Steady improvements in outcome have resulted in a growing number of BMT-HM survivors – a population that is uniquely vulnerable to long-term chronic health conditions (CHCs) that are directly related to the high-intensity therapeutic exposures (e.g., subsequent neoplasms, heart failure). In 2000, we constructed a retrospective cohort of 2,333 BMT recipients (City of Hope [COH] or University of Minnesota [UMN]; BMT: 1974-1998), who had survived ≥2y (BMT Survivor Study [BMTSS]; R01 CA78938, Bhatia). While BMTSS has successfully described the high burden of morbidity, accelerated aging and premature mortality in BMT-HM patients, the modest sample size (n=2,333) and the older transplant era (1974-1998) has limited the potential for new discoveries, especially in the face of evolving treatment strategies. We propose a significant enhancement of the existing BMTSS cohort to now include 10,042 HM patients treated with BMT between 1974 and 2014 at COH, UMN or UAB (BMT-HM), as well as a frequency-matched cohort of 3000 HM patients treated with conventional therapy without BMT (non-BMT-HM). This enhanced infrastructure (BMTSS- 2) will be poised to determine the burden of morbidity borne by HM patients treated with or without BMT within the context of individual HM diagnoses, and to understand the pathogenesis of treatment-related health conditions in the setting of accelerated aging. The enhanced BMTSS-2 infrastructure will enable us to: i) understand the long-term risk of health conditions experienced by HM patients treated with and without BMT; ii) determine the association between treatment exposures and health conditions; iii) determine trends in health conditions with changes in treatment strategies; iv) identify interactions between preventable modifiers (comorbidities, health behaviors) and treatment exposures when determining risk of health conditions; v) study the pathogenesis of treatment-related health conditions in the setting of accelerated aging, using genetic markers for susceptibility and epigenetic markers for the association of the health conditions with aging; vi) use HIPAA- compliant technology platform compatible with iOS/Android/iPad/Web-based applications to educate HM patients and measure health behaviors in real time. This is the largest and most comprehensive attempt at examining the health and wellbeing of HM patients treated with and without BMT. The overarching goal is to use BMTSS-2 for translational research along two tracks: A) develop risk prediction models to identify HM recipients at highest risk of treatment-related health conditions; and B) among those identified to be at highest risk, design and test targeted interventions to prevent/ ameliorate these debilitating chronic health conditions.

2017 年，估计有 130 万人患有血液恶性肿瘤（HM：白血病、骨髓瘤或淋巴瘤）在美国一线使用全身高强度化疗，有或没有放疗。是 HM 治疗的特点。事实上，通过更高强度的化疗/放疗和血液或骨髓移植 (BMT)，BMT 是可行的；成果的稳步改善带来了不断增长的 BMT-HM 幸存者数量——特别容易受到长期慢性健康状况影响的人群（CHC）与高强度治疗暴露直接相关（例如，随后的肿瘤、心脏 2000 年，我们构建了一个由 2,333 名 BMT 接受者（希望之城 [COH] 或大学）组成的回顾性队列明尼苏达州 [UMN]；BMT：1974-1998），存活 ≥2 年（BMT 幸存者研究 [BMTSS]；R01 CA78938， Bhatia），而 BMTSS 已成功描述了发病率高、加速衰老和早产的问题。 BMT-HM 患者的死亡率、较小的样本量 (n=2,333) 和较旧的移植时代 (1974-1998) 限制了新发现的潜力，特别是面对不断发展的治疗策略。现有 BMTSS 队列显着增强，目前包括 10,042 名接受 BMT 治疗的 HM 患者 1974 年至 2014 年间在 COH、UMN 或 UAB (BMT-HM) 以及 3000 名 HM 的频率匹配队列接受传统疗法但未进行 BMT 治疗的患者（非 BMT-HM），这增强了基础设施 (BMTSS-)。 2) 将准备好确定接受或不接受 BMT 治疗的 HM 患者所承受的发病负担个体 HM 诊断的背景，并了解治疗相关健康的发病机制在加速老化的情况下，增强的 BMTSS-2 基础设施将使我们能够： i) ii) 了解接受或不接受 BMT 治疗的 HM 患者所经历的健康状况的长期风险；确定治疗暴露与健康状况之间的关联； iii) 确定健康趋势；治疗策略发生变化的情况； iv) 确定可预防因素之间的相互作用（合并症、健康行为）和确定健康状况风险时的治疗暴露；使用遗传标记在加速衰老的情况下治疗相关健康状况的发病机制 vi) 使用 HIPAA- 来了解健康状况与衰老之间的关联的易感性和表观遗传标记；兼容 iOS/Android/iPad/Web 应用程序的兼容技术平台，用于教育 HM 患者并实时测量健康行为，这是最大、最全面的尝试。检查接受或未接受 BMT 治疗的 HM 患者的健康状况和福祉首要目标是使用 BMT。 BMTSS-2 用于沿着两个轨道进行转化研究：A) 开发风险预测模型来识别 HM 接受者与治疗相关的健康状况风险最高；以及 B) 在确定为风险最高的人群中，设计并测试有针对性的干预措施，以预防/改善这些使人衰弱的慢性健康状况。