Bone Marrow Failure Clinical Research Center

描述（由申请人提供）：特发性骨髓衰竭状态和细胞减少症（IBMFS&C）是一种罕见的疾病，其特征是造血祖细胞或干细胞衰竭，导致一种或全部血细胞谱系的产生不足。在所有这些疾病的许多情况下，免疫病理生理是一个统一的因素。先前的合作试验已经改善了再生障碍性贫血（AA）的有效药物治疗，但需要进行多中心研究来进一步提高再生障碍性贫血的疗效，特别是其他骨IBMFS，因为目前很少有有效的治疗方案。在此，我们建议在克利夫兰临床基金会（CCF）癌症中心成立IBMFS&C罕见病临床研究中心（RDCRC），包括由几个专业中心组成的联盟、患者倡导小组、数据和与数据技术协调中心（DTCC）合作。IBMFS&C RDCRC将重点关注AA、阵发性夜间血红蛋白尿、单系细胞减少症（包括大颗粒淋巴细胞白血病和纯红细胞发育不全）和各种骨髓增生异常综合征。本应用程序提出了一种多目标的方法来改善IBMFS&C的医疗治疗，包括：1)为每个IBMFS实施定义护理标准的治疗算法，2)系统地评估可能提高诊断准确性或对病理生理机制的理解的新型实验室分析，3)将患者纳入纵向随访研究，将新的和已建立的诊断变量与结果相关联，4)比较每种相关疾病的医疗和移植方法。5)针对目前缺乏良好治疗方案或标准治疗方法的亚群疾病制定实验性治疗方案；6)培训博士后为IBMFS&C开展临床试验和转化研究项目；7)培训社区医生进行IBMFS&C的诊断和管理；8)改善患者和医生的外展、教育和转诊资源。与再生障碍性贫血和MDS国际基金会（AAMDSIF）合作。由于PI的专业知识，加上CCF CC的经验和规模，CCF独特地定位为IBMFS&C中的RDCRC。一些知名专家组成了一个医疗中心联盟，这将是RDCRC的一个组成部分。为了进一步支持其活动，这项工作的额外基础设施将包括在联盟的每个中心组建一个罕见病办公室，专门的实验室测试点，临床试验的监督，DTCC的数据管理，以及AAMDSIF的患者转诊和教育。IBMFS&C RDCRC和联盟制定了一项计划，对研究员和社区医生进行IBMFS&C的教育。这些努力的成功将通过跟踪转诊到参与中心进行标准治疗，或在纵向和治疗方案中登记来部分评估。

DESCRIPTION (provided by applicant): Idiopathic bone marrow failure states and cytopenias (IBMFS&C) are rare disorders characterized by hematopoietic progenitor or stem cell failure resulting in deficient production of one, or all, blood cell lineages. Immune pathophysiology is a unifying factor in many cases of all these diseases. Prior collaborative trials have led to the improvement of effective medical therapy for aplastic anemia (AA), but ongoing multi-center studies are required to advance further the outcome for AA and especially the other bone IBMFS for which few useful treatment options exist. Here, we propose formation of the IBMFS&C Rare Disease Clinical Research Center (RDCRC) at The Cleveland Clinic Foundation (CCF) Cancer Center, encompassing a consortium of several specialized centers, patient advocacy group, and data and a collaboration with a data technology coordinating center (DTCC). The IBMFS&C RDCRC will focus on AA, paroxysmal nocturnal hemoglobinuria, single-lineage cytopenias including large granular lymphocyte leukemia and pure red cell aplasia, and various myelodysplastic syndromes. This application presents a multi-targeted approach to improving the medical therapy for IBMFS&C that includes: 1) implementing treatment algorithms for each IBMFS that define standards of care, 2) systematically evaluating novel laboratory assays that may improve the diagnostic accuracy or understanding of pathophysiologic mechanisms, 3) enrolling patients into a longitudinal follow-up study to correlate new and established diagnostic variables with outcome, 4) comparing medical and transplant approaches for each relevant disorder, 5) developing experimental treatment protocols for disease subsets currently without good treatment options or without a standard treatment approach, 6) training of post-doctoral fellows to develop clinical trials and translational research projects for the IBMFS&C, 7) educating community physicians in the diagnosis and management of the IBMFS&C, and 8) improving outreach, education and referral resources for patients and physicians, in collaboration with the Aplastic Anemia & MDS International Foundation (AAMDSIF). Due to the expertise of the PI, together with the experience and size of CCF CC, CCF uniquely is positioned to serve as an RDCRC in IBMFS&C. A number of leading experts formed a consortium of medical centers that will be an integral part of the RDCRC. To support further its activities, additional infrastructure for this effort will include a formation of a rare disease office in each of the centers of the consortium, specialized laboratory testing sites, oversight of clinical trials, data management by the DTCC, and patient referral and education by the AAMDSIF. The IBMFS&C RDCRC and the consortium have developed a plan for educating fellows and community physicians about IBMFS&C. The success of these efforts will be evaluated in part by tracking referrals to the participating centers for standard treatment, or enrollment in the longitudinal and treatment protocols.