Modeling Risk for Hypogammaglobulinemia, Infections, and Mortality with Chimeric Antigen Receptor (CAR) T-cell Therapy

项目摘要： 这项受资助的研究项目将促进我们对感染、发病率、 嵌合抗原受体(CAR)T细胞治疗后的死亡率。这项研究方案利用了大量的 对患者进行回顾性队列研究，以确定其对免疫学的影响和临床意义 CAR T细胞治疗后的低丙种球蛋白血症。将使用回归模型和网络分析来 确定感染发展和不良结局的风险因素，并制定临床风险预测 模特。在实现这些目标的过程中，巴梅特勒博士将解决我们免疫知识中的关键空白 使用CAR T细胞治疗后的调节失调，最终目的是改善患者的预后。 巴梅特勒博士将在卡洛斯·卡马戈教授的指导下进行这项工作，卡洛斯·卡马戈是一名国际专家 临床流行病学方面公认的专家，有出色的指导记录。巴梅特勒医生已经 组建了一支具有流行病学、生物统计学、B细胞免疫学专业知识的导师和合作者团队， CAR T细胞治疗和传染病，他们的支持将有助于该项目的成功。Dr。 巴梅特勒是哈佛医学院(HMS)的医学讲师和过敏医学助理。 马萨诸塞州总医院(MGH)的免疫学教授 对临床研究的坚定承诺。她以前在免疫缺陷和调查方面的培训和研究 其他B细胞靶向治疗的免疫学结果(包括迄今为止最大的利妥昔单抗治疗队列 已经建立了对实现她提出的研究目标至关重要的技能和经验。 本提案中概述的研究目标，以及合作机会和研究环境 MGH和HMS，将使Barmettler博士能够实现研究和教育目标，从而建立 她是一名独立的内科医生兼科学家，拥有先进生物统计技术和 免疫缺陷的机制。

Project Abstract: The funded research project will advance our understanding of immunologic risk factors for infections, morbidity, and mortality after chimeric antigen receptor (CAR) T-cell therapy. This research proposal utilizes a large retrospective cohort of patients to determine the immunologic impact and clinical significance of hypogammaglobulinemia following CAR T-cell therapy. Regression models and network analysis will be used to define risk factors for development of infections and poor outcomes and to develop a clinical risk prediction model. In accomplishing these aims, Dr. Barmettler will address critical gaps in our knowledge of immune dysregulation following the use of CAR T-cell therapy with the ultimate goal of improving patient outcomes. Dr. Barmettler will perform this work under the mentorship of Professor Carlos Camargo, an internationally recognized expert in clinical epidemiology with an outstanding track record of mentorship. Dr. Barmettler has assembled a team of mentors and collaborators with expertise in epidemiology, biostatistics, B-cell immunology, CAR T-cell therapy, and infectious disease, whose support will contribute to the success of this project. Dr. Barmettler is an Instructor in Medicine at Harvard Medical School (HMS) and Assistant in Medicine in Allergy- Immunology at Massachusetts General Hospital (MGH) who has demonstrated academic productivity and a strong commitment to clinical research. Her prior training and research in immune deficiency and investigating immunologic outcomes in other B-cell targeted therapies (including the largest cohort to date of rituximab-treated patients), have established the skills and experience critical for achieving her proposed research aims. The research aims outlined in this proposal, along with collaborative opportunities and research environment at MGH and HMS, will allow Dr. Barmettler to achieve the research and educational aims and to, thereby, establish herself as an independent physician-scientist with expertise in advanced biostatistical techniques and mechanisms of immune deficiency.