Washington University School of Medicine, Division of Pediatric Hematology Oncology, Department of Pediatrics, 660 S. Euclid Avenue, Campus Box 8116, St. Louis, MO 63110, USA.
Transfus Apher Sci. 2022 Oct;61(5):103554. doi: 10.1016/j.transci.2022.103554. Epub 2022 Aug 29.
Allogeneic hematopoietic stem cell transplant (HSCT) is the only established cure for sickle cell disease (SCD), a hemolytic disorder that arises due to a point mutation in the hemoglobin A gene. The result is an abnormal sickle hemoglobin (HbS) replacing hemoglobin A. Of the spectrum of sickle hemoglobinoapthies, homozygous (HbSS) and HbSβ thalassemia manifest severe forms of disease characterized by chronic endothelial injury/vasculopathy, ischemic pain, and vital organ damage that commence in childhood and escalate with age resulting in impaired quality of life, increased healthcare burden, and early mortality. HSCT has demonstrated durable disease control and regression of symptoms. Human leukocyte antigen (HLA) matched sibling donor (MSD) transplantation can achieve disease-free survival of > 90%. However, < 18% of SCD patients in the United States have a MSD. Familial mismatched and unrelated donors from registries provide alternate stem cell sources. Umbilical cord blood (UCB) from family or cord blood banks expand donor sources and are attractive due to donor-independent ease of use and availability. These naïve cells tolerate greater degrees of HLA-mismatch. The primary challenge with UCB is optimizing cell dose toward successful engraftment and timely immune reconstitution while minimizing graft-versus-host disease (GVHD). This review summarizes evidence that UCB remains a promising stem cell source where modern methods of graft expansion, conditioning, GVHD prophylaxis, and infection control can overcome these challenges and retain the value of this intervention.
异基因造血干细胞移植（HSCT）是治疗镰状细胞病（SCD）的唯一方法，镰状细胞病是一种由于血红蛋白 A 基因的点突变而引起的溶血性疾病。结果是异常的镰状血红蛋白（HbS）取代血红蛋白 A。在镰状血红蛋白病谱中，纯合子（HbSS）和 HbSβ 地中海贫血表现出严重的疾病形式，其特征是慢性内皮损伤/血管病变、缺血性疼痛和重要器官损伤，这些疾病始于儿童期，并随着年龄的增长而加剧，导致生活质量受损、医疗保健负担增加和早逝。HSCT 已证明可以持久控制疾病并缓解症状。人类白细胞抗原（HLA）匹配的同胞供体（MSD）移植可以实现无疾病生存>90%。然而，<18%的美国 SCD 患者有 MSD。来自登记处的家族性不匹配和无关供体提供了替代干细胞来源。来自家庭或脐带血库的脐带血（UCB）扩大了供体来源，并因其供体独立性、易于使用和可用性而具有吸引力。这些幼稚细胞可以耐受更大程度的 HLA 不匹配。UCB 的主要挑战是优化细胞剂量以实现成功植入和及时的免疫重建，同时最大限度地减少移植物抗宿主病（GVHD）。这篇综述总结了证据表明 UCB 仍然是一种有前途的干细胞来源，现代的移植扩增、调理、GVHD 预防和感染控制方法可以克服这些挑战并保持这种干预的价值。
