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/摘要 原发性免疫缺陷治疗联盟（PIDTC），44个免疫学的RDCRN财团和 2009年成立了整个美国和加拿大的造血干细胞移植中心 免疫系统的罕见遗传疾病，统称为原发性免疫缺陷疾病（PID）。 PIDTC的目标是了解PID并为其确定治疗定义最佳方法。在 PIDTC的最初9年已经研究了造血细胞移植（HCT），基因后的结果 治疗（GT）和酶替代疗法（ERT）针对严重合并免疫缺陷的患者 （SCID），Wiskott-Aldrich综合征（WAS）和慢性肉芽肿性疾病（CGD）。选择这些pids 因为它们一直是威胁生命最大和难以治疗的人之一，通常需要HCT才能生存。 因为没有一个中心遵循足够的受影响的人来涵盖这些疾病的全部范围，所以 财团对于定义每个PID的自然历史至关重要。而且，从历史上看，各个中心 开发了自己的治疗方法，没有关于HCT的适应症或时间的共识，类型 调理方案或供体细胞来源。因此，鲁棒统计需要多中心研究 评估以比较与患者相关变量的影响，还比较与治疗相关的变量的影响 临床结果。 PIDTC的组织是为了开发，执行和从多中心研究中学习。我们的专业 对理解PID发病机理的贡献，并定义哪种治疗产生最佳临床 结果已发表在111篇论文中。与多个患者倡导小组的密切关系 （PAG）已导致有关受影响个人及其家人的高优先级问题的出版物，包括质量 生活和长期结局。 PIDTC飞行员项目已经进行了SCID的新生儿筛查，并引入了 重要的机械研究，而我们的职业增强核心已经举行了年度PIDTC科学 研讨会和教育日，并支持了20名PID学员，他们都活跃于学术上 研究。 PIDTC对SCID的研究使我们的设计和实施是第一个前瞻性的 多中心试验，以确定最低剂量的busulfan条件以实现T和B细胞免疫 重组。展望未来，PIDTC将采取一项新的计划来研究主要的免疫调节 疾病（矮小）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 应用改进的基本理解，以实现PID护理的进一步基于证据的进步。