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克罗恩病的造血干细胞移植:最新治疗方法

Hematopoietic Stem Cell Transplantation in Crohn's Disease: State-of-the-Art Treatment.

作者信息

Hawkey C J

机构信息

Department of Gastroenterology, Nottingham Digestive Diseases Centre, Queens Medical Centre, Nottingham, Great Britain.

出版信息

Dig Dis. 2017;35(1-2):107-114. doi: 10.1159/000449090. Epub 2017 Feb 1.

DOI:10.1159/000449090
PMID:28147358
Abstract

Both autologous and allogeneic haemopoietic stem cell transplantation (HSCT) have been tried in Crohn's disease (CD). In allogeneic HSCT, the host bone marrow is ablated and replaced by bone marrow from a donor. This substitution of a genetically different bone marrow is effective in a number of conditions including those with an immunological basis such as CD. While the toxicity of allogeneic HSCT has precluded its uptake in idiopathic CD, there is interest in its utility in the management of early onset infantile (inflammatory bowel disease), which behaves as a monogenic disorder, with abnormalities of the interleukin 10 signalling system as the best recognized. In autologous HSCT, the patient's own stem cells are harvested before proceeding to lymphoablation and transplantation of the patient's own uncommitted stem cells, which generate an immune system with an altered T-cell repertoire. In a limited number of cases, this has led to substantial and prolonged remission tantamount to possible cure of CD. However, case series and controlled data from the Autologous Stem Cell International Crohn's Disease study suggest that although this method has its own advantages, most patients are still at risk of redeveloping CD, albeit with an arguably improved response to conventional treatment. The availability of new treatments for CD means that an HSCT is not a suitable treatment method for a majority of patients because of its greater toxicity, even though efficacy may be superior. Wider usage would depend upon the development of protocols that are safer and better targeted.

摘要

自体和异体造血干细胞移植(HSCT)均已在克罗恩病(CD)中进行尝试。在异体HSCT中,宿主骨髓被消融,由供体的骨髓替代。这种基因不同的骨髓替代在包括那些有免疫基础的疾病如CD中是有效的。虽然异体HSCT的毒性使其未被用于特发性CD,但人们对其在早发型婴儿期(炎症性肠病)管理中的效用感兴趣,这种疾病表现为单基因疾病,白细胞介素10信号系统异常是最广为人知的。在自体HSCT中,患者自身的干细胞在进行淋巴细胞清除和移植患者自身未定向的干细胞之前被采集,这些干细胞会产生具有改变的T细胞库的免疫系统。在少数情况下,这导致了实质性的、长期的缓解,等同于可能治愈CD。然而,来自国际自体干细胞克罗恩病研究的病例系列和对照数据表明,尽管这种方法有其自身优势,但大多数患者仍有CD复发的风险,尽管对传统治疗的反应可能有所改善。CD新治疗方法的出现意味着HSCT对大多数患者来说不是一种合适的治疗方法,因为其毒性更大,尽管疗效可能更好。更广泛的应用将取决于更安全、更有针对性方案的开发。

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