Primary Immune Deficiency Treatment Consortium

摘要/总结 原发性免疫缺陷治疗联盟（PIDTC）是一个由44名免疫学和 美国和加拿大的造血干细胞移植中心成立于2009年， 免疫系统的罕见遗传性疾病，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 在最初的9年里，PIDTC研究了造血细胞移植（HCT）、基因治疗和基因治疗后的结果。 酶替代疗法（ERT）治疗重症联合免疫缺陷患者 （SCID）、Wiskott-Aldrich综合征（WAS）和慢性肉芽肿病（CGD）。这些PID被选中 因为它们是最危及生命和最难治疗的疾病之一，通常需要HCT才能生存。 因为没有一个单一的中心跟踪足够多的受影响的个体来涵盖这些疾病的全部谱， 一个协会对于定义每个PID的自然历史是必不可少的。此外，从历史上看， 他们开发了自己的治疗方法，但对HCT的适应症或时间、类型 或者供体细胞的来源。因此，需要进行多中心研究， 评估不仅比较患者相关变量的影响，还比较治疗相关变量对 临床结果。PIDTC的组织是为了开发，执行和学习多中心研究。我们的主要 有助于了解PID发病机制和确定哪些治疗产生最佳的临床 已在111篇论文中发表成果。与多个患者倡导团体保持密切关系 （PAGs）导致出版了关于受影响个人及其家庭高度优先问题的出版物，包括质量问题， 生活和长期的结果。PIDTC试点项目推进了SCID的新生儿筛查， 重要的机制研究，而我们的职业提升核心已经举行了年度PIDTC科学 讲习班和教育日，并支持了20名PID学员，他们都仍然活跃在学术界 research. PIDTC对SCID的研究使我们能够设计和实施第一个前瞻性的 确定白消安预处理达到T和B细胞免疫的最小剂量的多中心试验 重组展望未来，PIDTC将采取新的举措，研究初级免疫调节 疾病（PIRD），因为它继续其研究的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，以实现进一步的循证进步，在护理PID。

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.