Department of Pathology and Cell Biology, Columbia University Irving Medical Center.
Department of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Irving Medical Center, New York, New York, United States.
Curr Opin Hematol. 2019 Nov;26(6):448-452. doi: 10.1097/MOH.0000000000000541.
Sickle cell disease (SCD) is a common monogenic disorder that is characterized by an A to T substitution in the β-globin gene that leads to the production of hemoglobin S (HbS). Polymerization of HbS leads to significant morbidity including vaso-occlusion, pain, hemolytic anemia, and end organ damage. Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment; however, suitable donors are not always readily available. This study reviews the current status of allo-HCT and autologous cellular therapies for SCD.
Alternative sources of allogeneic stem cells from unmatched donors such as cord blood and haploidentical donors are gaining traction. Early experience has shown that better conditioning regimens and graft-versus-host disease prophylaxis are needed before these donor sources can gain widespread use. Clinical trials are underway to determine the feasibility and efficacy of autologous transplantation with gene modified hematopoietic stem cells. Gene therapy strategies include HbS gene correction, gene addition, and hemoglobin F induction. Preliminary results are very encouraging.
Matched sibling allo-HCT for patients with SCD results in more than 90% overall survival and more than 80% event-free survival. Because only 25-30% of patients have a matched sibling donor, alternative donor options such as matched unrelated donors, related haploidentical donors and unrelated umbilical cord blood donors are being considered. Clinical trials investigating various strategies for gene therapy followed by autologous transplantation are underway. One major challenge is obtaining sufficient hematopoietic stem cells for gene therapy. Studies are being conducted on the optimal mobilization regimen and collection strategy.
镰状细胞病（SCD）是一种常见的单基因疾病，其特征在于β-珠蛋白基因中的 A 到 T 取代，导致血红蛋白 S（HbS）的产生。HSB 的聚合导致严重的发病率，包括血管阻塞、疼痛、溶血性贫血和终末器官损伤。异基因造血细胞移植（allo-HCT）是唯一的治愈性治疗方法；然而，合适的供体并不总是容易获得。本研究综述了 SCD 的 allo-HCT 和自体细胞治疗的现状。
来自非匹配供体的替代异基因干细胞来源，如脐带血和单倍体供体，正在受到关注。早期经验表明，在这些供体来源得到广泛应用之前，需要更好的调理方案和移植物抗宿主病预防。正在进行临床试验以确定基因修饰造血干细胞自体移植的可行性和疗效。基因治疗策略包括 HbS 基因校正、基因添加和血红蛋白 F 诱导。初步结果非常令人鼓舞。
SCD 患者的同胞 allo-HCT 导致总生存率超过 90%，无事件生存率超过 80%。由于只有 25-30%的患者有同胞供体，因此正在考虑替代供体选择，如匹配的无关供体、相关单倍体供体和无关脐带血供体。正在进行临床试验，以研究各种基因治疗策略，然后进行自体移植。一个主要挑战是获得足够的造血干细胞进行基因治疗。正在研究最佳动员方案和采集策略。
