BMT Survivor Study-2 (BMTSS-2)

BMT 幸存者研究 2 (BMTSS-2)

• 批准号: 10590723
• 负责人: SMITA BHATIA
• 金额: $ 126.69万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10590723
• 关键词: Acceleration; Address; Aftercare; Aging; Alabama; Android; Biological; Blood; Bone Marrow Transplantation; Cause of Death; Cessation of life; Chronic; Cities; Cohort Studies; 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; 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 Studies; Site; Source; Specimen; Survivors; Testing; Therapeutic; Time; Translational Research; Transplant Recipients; Transplantation; Umbilical Cord Blood; Universities; Validation; Vital Status; Work; chemotherapy; cohort; comorbidity; comparison group; conditioning; conventional therapy; demographics; design; epigenetic marker; experience; frailty; health care service utilization; high risk; human old age (65+); improved; indexing; leukemia; mortality; premature; prevent; procedure cost; relapse risk; repository; risk prediction model; stem cells; technology platform; transplant survivor; treatment risk; treatment strategy; trend; web app

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。全身高强度化疗联合或不联合放疗的一线使用 体现了HM管理的特点。疾病进展或复发风险高的患者接受治疗 进行更高强度的化疗/放疗以及血液或骨髓移植（BMT）；事实上，BMT 是 通常是这些患者唯一的治疗选择。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 失败）。 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， 巴蒂亚）。虽然 BMTSS 成功地描述了发病率高、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。我们提出一个 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 接受常规治疗但未进行 BMT 治疗的患者（非 BMT-HM）。这种增强的基础设施（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 加速老化的条件。增强的 BMTSS-2 基础设施将使我们能够： i) 了解接受或未接受 BMT 治疗的 HM 患者所经历的健康状况的长期风险；二） 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) 确定可预防修饰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； v) 研究 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 健康状况与衰老相关的易感性和表观遗传标记； vi) 使用 HIPAA- 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。这是最大规模、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。总体目标是使用 BMTSS-2 用于沿着两条轨道进行转化研究：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； B) 在那些被确定为风险最高的人中，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。

项目成果

Venous Thromboembolism in Autologous Blood or Marrow Transplantation Survivors: A Report from the Blood or Marrow Transplant Survivor Study.

自体血液或骨髓移植幸存者的静脉血栓栓塞：血液或骨髓移植幸存者研究报告。

• DOI: 10.1016/j.bbmt.2019.06.032
• 发表时间: 2019
• 期刊: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
• 作者: Gangaraju,Radhika;Chen,Yanjun;Hageman,Lindsey;Wu,Jessica;Francisco,Liton;Battles,Kevin;Kung,Michelle;Ness,Emily;Parman,Mariel;Weisdorf,DanielJ;Forman,StephenJ;Arora,Mukta;Armenian,SaroH;Bhatia,Smita
• 通讯作者: Bhatia,Smita

Neighborhood disadvantage, health status, and health care utilization after blood or marrow transplant: BMTSS report.

• DOI: 10.1182/bloodadvances.2022007548
• 发表时间: 2023-02-14
• 期刊: BLOOD ADVANCES
• 影响因子: 7.5
• 作者: Wolfson, Julie A.;Bhatia, Smita;Hageman, Lindsey;Ross, E. S.;Balas, Nora;Bosworth, Alysia;Te, Hok Sreng;Francisco, Liton;Funk, Erin;Hicks, Jessica;Landier, Wendy;Wu, Jessica;Siler, Arianna;Lim, Shawn;Wong, F. Lennie;Armenian, Saro H.;Arora, Mukta;Aswani, Monica S.
• 通讯作者: Aswani, Monica S.

Late mortality after bone marrow transplant for chronic myelogenous leukemia in the context of prior tyrosine kinase inhibitor exposure: A Blood or Marrow Transplant Survivor Study (BMTSS) report.

在先前的酪氨酸激酶抑制剂暴露的背景下，慢性粒细胞性白血病的骨髓移植后的晚期死亡率：血液或骨髓移植幸存者研究（BMTSS）报告。

• DOI: 10.1002/cncr.32443
• 发表时间: 2019-11-15
• 期刊: Cancer
• 影响因子: 6.2

Late-occurring venous thromboembolism in allogeneic blood or marrow transplant survivors: a BMTSS-HiGHS2 risk model.

• DOI: 10.1182/bloodadvances.2021004341
• 发表时间: 2021-10-26
• 期刊: Blood advances
• 影响因子: 7.5
• 作者: Gangaraju R;Chen Y;Hageman L;Wu J;Francisco L;Kung M;Weisdorf DJ;Forman SJ;Arora M;Armenian SH;Bhatia S
• 通讯作者: Bhatia S

Malignant Neoplasms of the Gastrointestinal Tract After Blood or Marrow Transplant.

血液或骨髓移植后胃肠道恶性肿瘤。

• DOI: 10.1001/jamaoncol.2022.6569
• 发表时间: 2023
• 期刊: JAMA oncology
• 影响因子: 28.4
• 作者: McDonald,Andrew;Dai,Chen;Meng,Qingrui;Hageman,Lindsey;Richman,Joshua;Wu,Jessica;Francisco,Liton;Ross,Elizabeth;Balas,Nora;Bosworth,Alysia;Te,HokSreng;Wong,FLennie;Landier,Wendy;Salzman,Donna;Bhatia,Ravi;Weisdorf,DanielJ