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

 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。我们的主要假设是，在患有严重SCD的成人中，采用完全相同的兄弟姐妹和完全匹配的非血缘关系供者HCT是可行的，并且具有可接受的安全性，两年无事件存活率至少为80%。为了验证这一假设，我们提出了以下具体目标：1.确定HCT在患有严重SCD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。我们将在15-40岁SCD的青少年和年轻人中进行一项HCT与标准支持性护理的对比临床试验。为此，我们组织了一个具有HCT或SCD专业知识的跨学科研究小组和一个数据协调中心，该中心在血液和骨髓移植临床试验网络(BMT-CTN)的临床试验方面非常有经验。这项试验将比较HCT后的结果与那些接受标准支持性护理的人的结果，这是这类血红蛋白疾病的第一次比较。我们将把60名有合适供体的患者分配到HCT组。我们将同时招募120-140名SCD患者，他们没有合适的供者加入平行比较队列。主要终点是HCT患者的2年无事件生存。次级终点将在修改的意向治疗分析中比较那些有或没有可用供者的患者的功能结果，包括心肺功能、努力耐受性、与健康相关的生活质量、疼痛、器官功能和SCD并发症。血细胞移植的特定结果和并发症，以及特定血统的供者嵌合体也将被研究。我们将建立一个所有符合条件的患者的长期随访队列，目的是 红细胞压积对SCD预后的长期影响的未来研究。如果成功，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.