Department of Pediatrics, Hackensack University Medical Center, Hackensack, NJ, USA.
Bone Marrow Transplant. 2012 Dec;47(12):1489-98. doi: 10.1038/bmt.2011.245. Epub 2011 Dec 19.
Sickle cell disease (SCD) is an autosomal recessive inherited hematological disorder characterized by chronic hemolysis and vaso-occlusion, resulting in multiorgan dysfunction and premature death. The only known curative therapy for patients with severe SCD is myeloablative conditioning and allo-SCT from HLA-matched sibling donors. In this state of the art review, we discuss current and future considerations including patient selection/eligibility, intensity of conditioning regimens, allogeneic graft sources, graft manipulation, mixed donor chimerism, organ function and stability and autologous gene correction stem cell strategies. Recent novel approaches to promote mixed donor chimerism have included the use of matched unrelated adult donors, umbilical cord blood donors, haploidentical familial donors and the utilization of nonmyeloablative, such as reduced intensity and reduced toxicity conditioning regimens. Future strategies will include gene therapy and autologous gene correction stem cell designs. Prospects are bright for novel stem and cellular approaches for patients with severe SCD, and we are currently at the end of the beginning for utilizing cellular therapeutics for the curative treatment of this chronic and debilitating condition.
镰状细胞病（SCD）是一种常染色体隐性遗传性血液系统疾病，其特征为慢性溶血和血管阻塞，导致多器官功能障碍和过早死亡。唯一已知的可治愈严重 SCD 患者的方法是同种异体造血干细胞移植（allo-SCT），来自 HLA 匹配的同胞供者。在这篇综述中，我们讨论了当前和未来的考虑因素，包括患者选择/资格、预处理方案的强度、同种异体移植物来源、移植物处理、混合供者嵌合体、器官功能和稳定性以及自体基因校正干细胞策略。最近促进混合供者嵌合体的新方法包括使用匹配的无关成人供者、脐带血供者、半相合家族供者以及非清髓性预处理，如减低强度和减低毒性预处理方案。未来的策略将包括基因治疗和自体基因校正干细胞设计。对于严重 SCD 患者来说，新型干细胞和细胞方法前景光明，我们目前正处于利用细胞治疗这种慢性和衰弱性疾病的开始阶段。
