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

项目摘要/摘要 本申请是为回应特别利益通知(NOSI)而提出的，该通知被确认为非- CA-22-057。对淋巴瘤生物学的更好理解有助于预测治疗反应和结果； 然而，这不能完全解释弱势群体的差异。在拉丁美洲(LATAM)，嗜淋巴 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， 与糟糕的结果相关。淋巴瘤流行病学结局(LEO)队列研究是最大的 世界上未来的NHL幸存者队列。然而，只有少数病毒驱动的非霍奇金淋巴瘤患者被 因此，注册后，限制了对这些罕见但致命疾病的了解的进步。EBV-和 与HTLV-1相关的淋巴瘤对LATAM和 美国，由于美国出现的病例数量较少，该领域的进展受到阻碍。 这项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；改进和开发特定人群的预后模型；推动当前 通过直接研究LATAM中流行的NHL亚型来认识罕见淋巴瘤；扩大种族/民族 通过招募大量西班牙裔和土著患者，实现非霍奇金淋巴瘤研究的多样性； 免疫基因组学在LATAM NHL研究中的应用在这项建议中，我们的目标是在 LEO队列研究和拉丁美洲淋巴增生性疾病组(Gell组)。考虑到 这一补充赠款的获奖期，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(INEN)，两家 秘鲁最大的癌症医院。在接下来的一年里，我们建议：目标1，开发一个临床病理数据库 收集80例HTLV-1/ATLL和80例EBV+DLBCL患者的资料，跟踪观察长期预后和 生存；目标2，建立研究肿瘤突变负担和基因表达特征的资源 这些病毒相关的非霍奇金淋巴瘤使用DNA和RNA测序；以及目标3，开发新的预测模型 通过检验不同临床变量和基因组数据对淋巴瘤预后的相对贡献 采用主成分和机器学习相结合的方法。弗劳尔斯博士和马尔皮卡博士有额外的资源 对AIM 2进行测序。这种方法将增强目前对病毒驱动的侵袭性NHL的了解 以临床数据和基因组学为特征的NHL患者的亚型和显著扩大的数量 超越狮子座。总之，这项提议提供了一个研究这些独特实体的特殊机会 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 利奥研究已经积累了12,000名NHL患者，并将为这些罕见但致命的患者产生新的数据 淋巴瘤对美国和LATAM的弱势人群造成了不成比例的影响。

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.