Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Blood. 2011 Aug 4;118(5):1197-207. doi: 10.1182/blood-2011-01-332510. Epub 2011 May 31.
Although sickle cell disease (SCD) has a variable clinical course, many patients develop end-organ complications that are associated with significant morbidity and early mortality. Myeloablative allogeneic HSCT (allo-HSCT) is curative but has been historically performed only in children younger than 16 years of age. Modest modifications in the conditioning regimen and supportive care have improved outcome such that the majority of children with a suitable HLA-matched sibling donor can expect a cure from this approach. However, adult patients have been excluded from myeloablative allo-HSCT because of anticipated excess toxicity resulting from accumulated disease burden. Efforts to use nonmyeloablative transplantation strategies in adults logically followed but were initially met with largely disappointing results. Recent results, however, indicate that nonmyeloablative allo-HSCT in adult patients with SCD allows for stable mixed hematopoietic chimerism with associated full-donor erythroid engraftment and normalization of blood counts, and persistence in some without continued immunosuppression suggests immunologic tolerance. The attainment of tolerance should allow extension of these potentially curative approaches to alternative donor sources. Efforts to build on these experiences should increase the use of allo-HSCT in patients with SCD while minimizing morbidity and mortality.
虽然镰状细胞病 (SCD) 的临床病程多变，但许多患者会出现终末器官并发症，这些并发症与显著的发病率和早期死亡率相关。清髓性异基因造血干细胞移植 (allo-HSCT) 是一种根治性治疗方法，但历史上仅在 16 岁以下的儿童中进行。在预处理方案和支持性护理方面进行适度的修改，改善了结果，使得大多数有合适 HLA 匹配同胞供体的儿童可以通过这种方法治愈。然而，由于预期累积疾病负担导致的毒性增加，成人患者被排除在清髓性 allo-HSCT 之外。因此，人们逻辑上尝试使用非清髓性移植策略来治疗成人患者，但最初的结果大多令人失望。然而，最近的结果表明，SCD 成人患者的非清髓性 allo-HSCT 可以实现稳定的混合造血嵌合体，并伴有完全供体红细胞植入和血细胞计数正常化，在一些患者中无需持续免疫抑制即可维持这种状态，这表明存在免疫耐受。获得耐受应该允许将这些潜在的根治性方法扩展到其他供体来源。在这些经验的基础上进行努力，应该可以增加 allo-HSCT 在 SCD 患者中的应用，同时最大限度地降低发病率和死亡率。
