Primary Immune Deficiency Treatment Consortium

初级免疫缺陷治疗联盟

• 批准号: 9804604
• 负责人: Donald B Kohn
• 金额: $ 160.46万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-12 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9804604
• 关键词: Address; Affect; Age of Onset; Autoimmune Process; B-Lymphocytes; Biological; Biological Markers; Biological Products; Busulfan; Canada; Caring; Cells; Chimerism; Chronic Granulomatous Disease; Clinical; Clinical Management; Consensus; Data; Diagnosis; Disease; Dose; Education; Educational workshop; Effectiveness; Family; Fellowship; Fostering; Freedom; Funding; Future; Gene Mutation; Genes; Genotype; Goals; Growth; Health; Hematopoietic Stem Cell Transplantation; Immune; Immune System Diseases; Immune system; Immunology; Indium-111; Individual; Institutional Review Boards; Intervention Trial; Intestines; Knowledge; Late Effects; Learning; Life; Mendelian disorder; Molecular Target; Monitor; Multi-Institutional Clinical Trial; Multicenter Studies; Multicenter Trials; Mutation; Natural History; Neonatal Screening; Outcome; Outcome Study; Paper; Parents; Pathogenesis; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacology; Pilot Projects; Primary Health Care; Protocols documentation; Publications; Publishing; Quality of life; Rare Diseases; Recurrence; Regimen; Research; Research Personnel; Sampling; Scientist; Severe Combined Immunodeficiency; Severities; Source; Structure; T-Lymphocyte; Time; Training; Treatment outcome; Wiskott-Aldrich Syndrome; Work; autoinflammation; autoinflammatory; base; career; conditioning; congenital immunodeficiency; crowdsourcing; design; enzyme replacement therapy; evidence base; gene discovery; gene therapy; graft vs host disease; gut microbiome; hematopoietic cell transplantation; high risk; immune reconstitution; immunoregulation; improved; innovation; metabolome; optimal treatments; organizational structure; patient advocacy group; population based; prevent; programs; prospective; rare genetic disorder; response; small molecule; transplant centers

ABSTRACT/SUMMARY The Primary Immune Deficiency Treatment Consortium (PIDTC), an RDCRN consortium of 44 immunology and hematopoietic stem cell transplant centers throughout the USA and Canada, was established in 2009 to study rare genetic disorders of the immune system, collectively known as primary immunodeficiency diseases (PIDs). The goals of the PIDTC are to understand PIDs and define optimal approaches for their definitive treatment. In its first 9 years, the PIDTC has studied outcomes following hematopoietic cell transplantation (HCT), gene therapy (GT) and enzyme replacement therapy (ERT) for patients with severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD). These PIDs were chosen because they have been among the most life-threatening and difficult to treat, often requiring HCT for survival. Because no single center follows enough affected individuals to encompass the full spectrum of these disorders, a consortium is essential to define the natural history of each PID. Moreover, historically, individual centers developed their own approaches to treatment, without consensus regarding indications or timing for HCT, types of conditioning regimens, or sources of donor cells. Thus, multicenter studies are required for robust statistical assessment to compare impacts not only of patient-related variables, but also of treatment-related variables on clinical outcome. The PIDTC is organized to develop, perform and learn from multicenter studies. Our major contributions to understanding of PID pathogenesis and defining which treatments produce optimal clinical outcomes have been published in 111 papers. Close relationships with multiple Patient Advocacy Groups (PAGs) have led to publications on high-priority issues for affected individuals and their families, including quality of life and long-term outcomes. PIDTC Pilot Projects have advanced newborn screening for SCID and introduced important mechanistic studies, while our Career Enhancement Core has held an annual PIDTC Scientific Workshop and Education Day and has supported 20 PID trainees, all of whom remain active in academic research. PIDTC studies of SCID have enabled our design and implementation of the first prospective multicenter trial to determine the minimal dose of busulfan conditioning to achieve T and B cell immune reconstitution. Looking forward, the PIDTC will undertake a new initiative to study Primary Immune Regulatory Disorders (PIRD) as it continues its studies of SCID and CGD. The major impact of the proposed research will be establishment of baseline data and organizational structures to undertake multicenter clinical trials that will apply improved basic understanding to achieve further evidence-based advances in the care of PIDs.

摘要/总结 原发性免疫缺陷治疗联盟 (PIDTC)，一个由 44 个免疫学和 遍布美国和加拿大的造血干细胞移植中心成立于 2009 年，旨在研究 罕见的免疫系统遗传性疾病，统称为原发性免疫缺陷病（PID）。 PIDTC 的目标是了解 PID 并确定其最终治疗的最佳方法。在 成立的前 9 年，PIDTC 研究了造血细胞移植 (HCT)、基因 严重联合免疫缺陷患者的治疗（GT）和酶替代疗法（ERT） (SCID)、Wiskott-Aldrich 综合征 (WAS) 和慢性肉芽肿病 (CGD)。这些PID被选择 因为它们是最危及生命且最难治疗的疾病之一，通常需要 HCT 才能生存。 因为没有一个中心跟踪足够多的受影响个体来涵盖这些疾病的全部范围， 一个联盟对于定义每个 PID 的自然历史至关重要。此外，从历史上看，个别中心 制定了自己的治疗方法，但没有就 HCT 的适应症或时机、类型达成共识 预处理方案或供体细胞的来源。因此，需要多中心研究来进行稳健的统计 评估不仅可以比较患者相关变量的影响，还可以比较治疗相关变量对患者的影响 临床结果。 PIDTC 的组织目的是开发、执行多中心研究并从中学习。我们的专业 对理解 PID 发病机制和确定哪些治疗产生最佳临床效果的贡献 成果已发表论文111篇。与多个患者权益团体保持密切关系 (PAG) 已出版有关受影响个人及其家庭的高度优先问题的出版物，包括质量问题 的生活和长期结果。 PIDTC 试点项目对 SCID 进行了先进的新生儿筛查，并推出了 重要的机制研究，而我们的职业提升核心每年举办 PIDTC 科学会议 研讨会和教育日，并为 20 名 PID 学员提供了支持，他们都仍然活跃在学术领域 研究。 SCID 的 PIDTC 研究使我们能够设计和实施第一个前瞻性 确定白消安调理实现 T 和 B 细胞免疫的最小剂量的多中心试验 重构。展望未来，PIDTC 将采取新举措来研究初级免疫监管 疾病 (PIRD)，继续研究 SCID 和 CGD。拟议研究的主要影响将 建立基线数据和组织结构以进行多中心临床试验 运用改进的基本理解，在 PID 治疗方面取得进一步的循证进展。