The Lymphoma Epidemiology of Outcomes (LEO) Cohort Study (Supplement)

淋巴瘤流行病学结果 (LEO) 队列研究（补充）

• 批准号: 10626269
• 负责人: JAMES R CERHAN
• 金额: $ 19.56万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10626269
• 关键词: Address; Adult T-Cell Leukemia/Lymphoma; Affect; Award; Biology; Cancer Hospital; Clinical; Clinical Data; Cohort Studies; Collaborations; Country; DNA sequencing; Data; Databases; Disease; Enrollment; Epidemiology; Flowers; Gene Expression Profile; Genomics; Goals; Grant; Hispanic; Hospitals; Human Herpesvirus 4; Human T-lymphotropic virus 1; Immunogenomics; Indigenous; Institution; Knowledge; Latin America; Latin American; Lymphoma; Lymphoproliferative Disorders; Machine Learning; Minority; Modeling; Mutation; Non-Hodgkin' s Lymphoma; Outcome; Outcome Study; Patients; Peru; Population; Prediction of Response to Therapy; Prognosis; Prospective cohort; Research; Resources; Sampling; Underserved Population; Viral; Virus; Vulnerable Populations; Work; ethnic diversity; experience; genomic data; improved; interest; large cell Diffuse non-Hodgkin' s lymphoma; non-Hodgkin' s lymphoma patients; novel; prognostic model; prognostication; racial and ethnic; recruit; response; survivorship; therapy outcome; transcriptome sequencing; tumor

PROJECT SUMMARY/ABSTRACT This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT- CA-22-057. A better understanding of lymphoma biology has aided in predicting therapy responses and outcomes; however, this cannot entirely explain differences in vulnerable populations. In Latin America (LATAM), lymphotropic viruses (i.e., HTLV-1, EBV) are a common cause of aggressive non-Hodgkin lymphoma (NHL) subtypes and are associated to poor outcomes. The Lymphoma Epidemiology of Outcomes (LEO) cohort study is the largest prospective cohort of NHL survivors in the world. However, only few patients with virally-driven NHL have been enrolled, therefore, limiting the advancement on the knowledge of these rare but fatal diseases. Both EBV- and HTLV-1-associated lymphomas disproportionately affect racial/ethnic underserved populations in LATAM and the U.S., with advancements in the field being precluded by the low numbers of cases seen in the U.S. The overall goals of this supplemental application are to directly extent our ongoing research by expanding the number of NHL subtypes currently registered; improve and develop population-specific prognostic models; advance the current knowledge on rare lymphomas by directly studying NHL subtypes prevalent in LATAM; expand the racial/ethnic diversity of NHL research by recruiting a large number of Hispanic and Native Indigenous patients; and introduce immunogenomics to the study of NHL in LATAM. In this proposal, we aim to establish a partnership between the LEO cohort study and the Latin American Group of Lymphoproliferative Disorders (GELL group). Considering the award period for this supplemental grant, the estimated number of virally-driven NHL subtypes seen per center, and our prior experience collaborating with these centers, we propose to work with two cancer hospitals in Lima, Peru, the Hospital Edgardo Rebagliati and the Instituto Nacional de Enfermedades Neoplasicas (INEN), the two largest cancer hospitals in Peru. Over the next year we propose to: aim 1, develop a clinicopathological database to capture data of 80 HTLV-1/ATLL and 80 EBV+ DLBCL, NOS patients followed for long-term prognosis and survivorship; aim 2, build the resource to investigate the tumor mutational burden and gene expression signature of these viral-associated NHL using DNA and RNA sequencing; and aim 3, develop novel prognostication models by examining the relative contribution of the different clinical variables and genomic data on lymphoma outcomes using principal component and machine learning approach. Drs. Flowers and Malpica have additional resources to perform sequencing for aim 2. This approach will enhance the current knowledge of virally-driven aggressive NHL subtypes and dramatically expand the number of NHL patients characterized with clinical data and genomics beyond LEO. In conclusion, this proposal addresses an exceptional opportunity to research these unique entities in a collaboration across 10 academic institutions in the U.S. and Peru. This work leverages data and samples from >12,000 NHL patients already accrued by the LEO study and will generate novel data for these rare but fatal lymphomas that disproportionately affects vulnerable populations in the U.S. and LATAM.

项目总结/摘要 本申请是为了回应特别利益通知（NOSI）而提交的，该通知被确定为不- CA-22-057更好地了解淋巴瘤生物学有助于预测治疗反应和结果; 然而，这并不能完全解释弱势群体的差异。在拉丁美洲（LATAM），嗜淋巴细胞 病毒（即，HTLV-1，EBV）是侵袭性非霍奇金淋巴瘤（NHL）亚型的常见原因， 与不良结局有关。淋巴瘤流行病学结局（LEO）队列研究是最大的 NHL幸存者的前瞻性队列。然而，只有少数病毒驱动的NHL患者接受了治疗。 因此，登记的人数限制了对这些罕见但致命疾病的认识的进步。EBV-和 HTLV-1相关淋巴瘤不成比例地影响拉丁美洲和加勒比地区的种族/民族服务不足人群 美国，由于美国的病例数量较少，该领域的进展受到阻碍。 本补充申请的目标是通过扩大NHL的数量来直接扩展我们正在进行的研究 目前登记的亚型;改善和发展人群特异性预后模型;推进目前的 通过直接研究拉丁美洲流行的NHL亚型了解罕见淋巴瘤;扩大种族/民族 通过招募大量的西班牙裔和原住民患者来实现NHL研究的多样性;并引入 免疫基因组学在拉丁美洲NHL的研究。在本提案中，我们的目标是在 LEO队列研究和拉丁美洲肿瘤增生性疾病组（GELL组）。考虑 该补充补助金的授予期，每个中心看到的病毒驱动的NHL亚型的估计数量， 根据我们之前与这些中心合作的经验，我们建议与利马的两家癌症医院合作， 秘鲁、Edgardo Rebagliati医院和国家肿瘤研究所， 秘鲁最大的癌症医院在接下来的一年里，我们建议：目标1，建立一个临床病理学数据库 为了获取80例HTLV-1/ATLL和80例EBV+ DLBCL的数据，对NOS患者进行了长期预后随访， 生存率;目标2，建立研究肿瘤突变负荷和基因表达特征的资源 这些病毒相关的NHL使用DNA和RNA测序;和目的3，开发新的预测模型 通过检查不同临床变量和基因组数据对淋巴瘤结局的相对贡献， 使用主成分和机器学习方法。弗劳尔斯博士和马尔皮卡有额外的资源 对目标2进行排序。这种方法将提高目前的知识，病毒驱动的侵略性NHL 亚型和显着扩大NHL患者的数量，其特征在于临床数据和基因组学 超越LEO总之，本提案提供了研究这些独特实体的绝佳机会 在美国和秘鲁的10个学术机构的合作下。这项工作利用了来自 LEO研究已经累积了超过12，000名NHL患者，并将为这些罕见但致命的NHL患者产生新的数据。 淋巴瘤不成比例地影响美国和拉丁美洲的弱势群体。