A phase II trial to assess Haploidentical a/ß T-depleted stem cell transplantation in patients with sickle cell disease with no available sibling donor - Acronym: T-HAPLO-SCT for SCD

镰状细胞病(SCD)是一个世界性的健康问题，每年有30多万名儿童出生，仍然是一种发病率和死亡率都很高的疾病。移民使SCD成为西方国家日益突出的问题。这种疾病在欧洲某些地区超过了血友病和囊性纤维化，是一种进行性慢性多器官疾病。卒中是SCD的主要衰弱并发症，也是儿童卒中最常见的原因。30%的人会患上无症状中风，导致儿童认知障碍和生活质量下降。匹配同胞捐献者(MSD)造血干细胞移植(HSCT)是金标准，也是唯一有效的治疗方法，5年内无移植失败，存活率为90%。但只有20%的患者可以获得MSD，与无关供者进行HSCT导致移植物抗宿主病(GvHD)的发生率高得令人无法接受。来自亲属的T细胞耗尽半相合HSCT(T-Haplo-HSCT)可以治愈其余80%的患者，其中大部分是父母，但也有半相合的兄弟姐妹和表亲。这项试验旨在证明，在结局和治疗相关的发病率和死亡率方面，来自亲属的单倍体相合干细胞移植与兄弟姐妹捐赠者的HSCT是相同的。已确定HSCT适应症的患者将被分层，如果有的话，将接受同胞捐赠者移植。如果不是，患者将接受单倍体相合亲属的移植。除了干细胞来源，这两组人将接受几乎相同的治疗。我们希望证明T-Haplo-HSCT是安全的，在总体、无疾病和无GvHD的存活率方面，可以达到与MSD移植相当的结果。其目的是，为每一位患有镰状细胞疾病的患者提供治疗。

Sickle cell disease (SCD) represents a worldwide health problem with over 300,000 affected children born each year and remains a disease with high morbidity and mortality. Migration makes SCD an increasingly eminent problem of western countries. The disease is overtaking haemophilia and cystic fibrosis in certain parts of Europe and is a progressive chronic multi-organ disease. Stroke is the major debilitating complication of SCD and the most frequent cause of stroke in children. 30% develop silent strokes leading to cognitive impairment in children and poor quality of life. Matched sibling donor (MSD) hematopoietic stem cell transplantation (HSCT) is the gold standard and the only curative treatment available, with a 90% survival without graft failure at 5 years. But MSD are available for only 20% of patients and HSCT with unrelated donors resulted in unacceptably high rates of graft-versus-host disease (GvHD). T-cell depleted haploidentical HSCT (T-Haplo-HSCT) from relatives, mostly parents, but also haplo-matched siblings and cousins could offer cure to the remaining 80% of affected patients. This trial aims to demonstrate that a haploidentical stem cell transplantation from a relative is equivalent to a sibling donor HSCT with regard to outcome and treatment related morbidity and mortality. Patients with an established indication for HSCT will be stratified and will receive a sibling donor transplantation if available. If not, the patient will receive a transplant from a haploidentical relative. With the exception of the stem cell source, both groups will receive an almost identical treatment. We expect to show that T-Haplo-HSCT is safe and can achieve a comparable outcome to a MSD transplantation with regard to overall, disease-free and GvHD-free survival. The intention is, to offer cure to every patient affected with sickle cell disease.