Allogeneic hematopoietic stem cell transplantation for sickle cell disease: the time is now
Allogeneic hematopoietic stem cell transplantation for sickle cell disease: the time is now
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DOI：
10.1182/blood-2011-01-332510
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发表时间：
2011-08-04
期刊：
影响因子：
20.3
通讯作者：
Tisdale, John F.
中科院分区：
文献类型：
--
作者：
Hsieh, Matthew M.;Fitzhugh, Courtney D.;Tisdale, John F.
尽管镰状细胞病 (SCD) 的临床病程各不相同，但许多患者会出现与显着发病率和早期死亡率相关的终末器官并发症。清髓性同种异体 HSCT (allo-HSCT) 具有治愈性，但历史上仅在 16 岁以下的儿童中进行。对预处理方案和支持性护理的适度修改已经改善了结果，因此大多数拥有合适的 HLA 匹配兄弟姐妹捐赠者的儿童都可以通过这种方法得到治愈。然而，成年患者已被排除在清髓性同种异体造血干细胞移植之外，因为预计累积的疾病负担会导致过度毒性。人们顺理成章地在成人中使用非清髓性移植策略，但最初的结果却令人失望。然而，最近的结果表明，成年 SCD 患者的非清髓性异基因 HSCT 可以实现稳定的混合造血嵌合，并伴有相关的全供体红细胞植入和血细胞计数正常化，并且在一些没有持续免疫抑制的情况下持续存在表明免疫耐受。耐受性的实现应允许将这些潜在的治疗方法扩展到其他捐助来源。基于这些经验的努力应该增加 SCD 患者异基因造血干细胞移植的使用，同时最大限度地降低发病率和死亡率。 （血。2011；118(5):1197-1207）
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. (Blood. 2011;118(5):1197-1207)