Hematopoietic Stem Cell Transplantation for Young Adults with SCD - DCC

 描述(申请人提供)：在儿童时期制定的支持性保健措施成功地预防了镰状细胞病(SCD)的严重感染和许多其他危及生命的并发症，从而提高了成年后的存活率。这在一定程度上改变了SCD的人口结构，将越来越多的患有慢性健康损害的年轻人包括在内。虽然造血细胞移植(HCT)具有治愈潜力，但很少有SCD患者接受HCT治疗，部分原因是这种治疗的毒性。最近，人类白细胞抗原(HLA)分型技术的进步和支持性治疗改善了HCT的预后，特别是在无血缘关系的供者HCT之后。我们组织了一个由移植研究人员和成人镰刀细胞提供者组成的跨学科小组，以及一个在进行骨髓移植临床试验网络的临床试验方面非常有经验的DAA协调中心，以验证这样一个假设，即来自人类白细胞抗原相合同胞或无关骨髓捐赠者的HCT是安全有效的，对患有严重SCD的年轻人是安全有效的，两年无事件存活率至少为80%。我们已经在成人SCD患者的骨髓移植的初步研究中测试了该调理方案招募的可行性和安全性。我们建议在一项临床试验中验证这一假设，即将HCT后的结果与接受标准支持性护理的人观察到的结果进行比较，这是第一次在血红蛋白疾病中进行这种比较。我们将60名年龄在15-40岁、有合适供者的患者分配到骨髓移植组，同时将120-140名没有合适供者的SCD患者纳入平行对照队列。我们建议对患有严重镰状细胞疾病的成年人进行HCT的研究，具体目的如下：1.确定HCT在患有严重镰状细胞疾病的年轻人中的安全性和有效性。2.测量供者造血对功能结局和终末器官功能的影响。我们将建立所有符合条件的患者的长期随访队列，以便将来研究HCT对SCD预后的长期影响。如果成功，拟议的对比临床试验将是第一个比较HCT和支持性治疗SCD的试验，并可能扩大患有严重SCD的成年人的治疗机会。

 DESCRIPTION (provided by applicant): Supportive health care measures instituted during childhood successfully prevent serious infections and many other life-threatening complications of sickle cell disease (SCD), resulting in improved survival to adulthood. This has, in part, shifted the demographics of SCD to include a growing proportion of young adults with chronic health impairments. While hematopoietic cell transplantation (HCT) has curative potential, very few individuals with SCD are treated by HCT, due in part to the toxicity of this treatment. Recently, advances in Human Leukocyte Antigen (HLA) typing techniques and supportive care have improved outcomes of HCT, particularly after unrelated donor HCT. We have organized an interdisciplinary group of transplant investigators and adult sickle cell providers as well as a daa coordinating center very experienced in the conduct of clinical trials for the BMT clinical trials network to test the hypothesis that HCT from an HLA-identical sibling or unrelated marrow donor with a conditioning regimen of Busulfan, Fludarabine and anti-thymocyte is safe and effective in young adults with severe SCD with a two year event free survival of at least 80%. We have tested the feasibility of recruitment and safety of the conditioning regimen in a pilot study of BMT in adults with SCD. We propose to test this hypothesis in a clinical trial that it wil compare outcomes after HCT to outcomes observed in those who receive standard supportive care, the first comparison of this kind in hemoglobin disorders. We will assign 60 patients age 15-40 years who have an available suitably matched donor to the BMT arm and will contemporaneously enroll 120-140 SCD who do not an available suitable donor to a parallel comparison cohort. We propose to investigate HCT in adults with severe sickle cell disease by the following specific aims: 1. Determine the safety and efficacy of HCT in young adults with severe sickle cell disease. 2. Measure the impact of donor hematopoiesis on functional outcomes and end-organ function. We will establish a long term follow up cohort of all eligible patients for the purpose of future studies of long term impact of HCT on outcome sin SCD. If successful, the proposed comparative clinical trial would be the first to compare HCT and supportive care for SCD, and could broaden the therapeutic opportunities for adults with severe SCD.