Hematopoietic Stem Cell Transplantation for Young Adults with Sickle Cell Disease - Clinical Coordinating Center

 描述（由申请人提供）：在儿童时期采取的支持性医疗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生存率。这在一定程度上改变了SCD的人口统计数据，包括越来越多的患有慢性健康障碍的年轻人。虽然造血干细胞移植（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）分型技术和支持性治疗的进步改善了HCT的结果，特别是在无关供体HCT后。我们的总体假设是，HLA完全相同的同胞和良好匹配的无关供体HCT在患有严重SCD的成人中是可行的，并且具有可接受的安全性特征，2年无事件生存率至少为80%。为了验证这一假设，我们提出了以下具体目标：1。确定HCT在严重SCD年轻成人中的安全性和有效性。2.测量供体造血对功能结局和终末器官功能的影响。我们将在15-40岁的青少年和年轻成人SCD患者中开展一项HCT与标准支持治疗的比较临床试验。为此，我们组织了一个由HCT或SCD专业知识的研究人员组成的跨学科小组，以及一个在血液和骨髓移植临床试验网络（BMT-CTN）临床试验实施方面经验丰富的数据协调中心。这项试验将比较HCT后的结果与接受标准支持治疗的患者的结果，这是血红蛋白病的首次此类比较。我们将60名有合适供体的患者分配到HCT组，同时将120-140名没有合适供体的SCD患者纳入平行对照队列。主要终点是HCT患者的2年无事件生存期。次要终点将在改良的意向治疗分析中比较有或无可用供体的患者的功能结局，包括心肺功能、努力耐受性、健康相关生活质量、疼痛、器官功能和SCD并发症。还将研究HCT特异性结局和并发症以及谱系特异性供体嵌合体。我们将对所有符合条件的患者建立一个长期随访队列， HCT对SCD结局的长期影响的未来研究。如果成功的话，这项研究可以确立HCT在成人严重SCD治疗中的地位，并扩大治疗机会。

 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 stem 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. Our overarching hypothesis is that HLA identical sibling and well- matched unrelated donor HCT in adults with severe SCD is feasible and has an acceptable safety profile with a 2-year event free survival of at least 80%. In order to test this hypothesis we propose the following specific aims: 1. Determine the safety and efficacy of HCT in young adults with severe SCD. 2. Measure the impact of donor hematopoiesis on functional outcomes and end-organ function. We will conduct a comparative clinical trial of HCT vs. standard supportive care in adolescents and young adults with SCD age 15-40 years of age. For this purpose we have organized an interdisciplinary group of investigators with expertise in HCT or SCD and a data-coordinating center very experienced in the conduct of clinical trials for the Blood and marrow transplant clinical trials network (BMT-CTN). This trial will compare outcomes after HCT to outcomes observed in those who receive standard supportive care, the first comparison of this kind in hemoglobinopathies. We will assign 60 patients who have an available suitably matched donor to the HCT arm. We will contemporaneously enroll 120-140 SCD who do not have an available suitable donor to a parallel comparison cohort. The primary endpoint is 2-year event free survival in the HCT patients. Secondary endpoints will compare functional outcomes including cardiopulmonary function, effort tolerance, health related quality of life, pain, organ function and SCD complications in those with or without an available donor, in a modified intent to treat analysis. HCT specific outcomes and complications, and lineage specific donor chimerism will also be studied. 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 outcomes in SCD. If successful, this study could establish the place of HCT in and broaden the therapeutic opportunities for the treatment of adults with severe SCD.