Ph2 of T-Cell Depl Familial Haploidentical SCT for tx Hi-Risk Sickle Cell Anemia

描述(由申请人提供)： 镰状细胞病是一种孤儿疾病，具有高危特征的患者，包括有脑血管病史和/或肺和/或肺血管并发症的患者，预后较差，有较高的严重慢性病和过早死亡的倾向。唯一的治愈和稳定器官的疗法是从未受影响的人类白细胞抗原(HLA)匹配的同胞捐赠者中进行异基因干细胞移植(AllSCT)。然而，只有大约15%的SCD患者有这样的捐赠者。替代异基因供体来源包括未受影响的FHI捐赠者。移植物抗宿主病(GVHD)和/或移植物衰竭的风险增加，限制了这种供体来源的使用。然而，这些风险可以通过使用T细胞耗竭(TCD)来最小化，方法是阳性选择CD34+造血干细胞，然后是最小的T细胞回补。利用CD34+造血干细胞阳性选择的FHI TCD异体干细胞移植已被证明在高危血液系统恶性肿瘤患者中是成功的。目前，FDA还没有关于该设备/程序用于非恶性疾病(如SCD)的适应症。具体目标包括：1)确定宿主骨髓免疫抑制条件(MIC)在高危SCD患者中应用的安全性和可行性；2)持续供者全血和红细胞嵌合；3)免疫细胞重建和功能的质量和数量；4)神经和神经认知后遗症的变化；5)肺和肺血管功能的差异；以及6)健康相关生活质量(HRQL)的变化。

DESCRIPTION (provided by applicant): Sickle cell disease is an orphan disease and patients with high-risk features, including those with a history of cerebral vasculopathy and/or pulmonary and/or pulmonary vascular complications portend to have a poor prognosis with a high tendency toward serious chronic morbidities and premature death. The only curative and organ stabilizing therapy is allogeneic stem cell transplantation (AlloSCT) from unaffected human leukocyte antigen (HLA) matched sibling donors. However, only approximately 15% of SCD patients have such donors. An alternate allogeneic donor source includes unaffected FHI donors. The use of this donor source is limited by increased risks of graft-versus-host disease (GVHD) and/or graft failure. However, these risks can be minimized by the use of T cell depletion (TCD) through positive selection of CD34+ hematopoietic stem cells followed by minimal T cell addback. FHI TCD AlloSCT utilizing CD34+ hematopoietic stem cell positive selection has been demonstrated to be successful in patients with high-risk hematological malignancies. Currently there is no FDA indication for this device/procedure for non-malignant diseases, such as SCD. The specific objectives include: 1) to determine safety and feasibility of host myeloimmunosuppressive conditioning (MIC) followed by FHI TCD AlloSCT in high-risk patients with SCD; 2) sustained donor whole blood and red blood cell chimerism; 3) quality and quantity of immune cell reconstitution and function; 4) changes in neurological and neurocognitive sequelae; 5) differences in pulmonary and pulmonary vascular function; and 6) changes in health-related quality of life (HRQL).