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非清髓性(小移植)后的异基因造血干细胞治疗

[Allogeneic hematopoietic stem cell treatment after non-myeloablation (minigraft)].

作者信息

Baron F

机构信息

Université de Liège et Fonds National de la Recherche scientifique - F.N.R.S.

出版信息

Bull Mem Acad R Med Belg. 2011;166(1-2):39-45; discussion 46-8.

Abstract

Allogeneic haematopoietic stem cell transplantation is the best treatment option for many patients suffering from severe haematologic diseases. Allogeneic transplantation is generally preceded, by a myeloablative conditioning regimen consisting of high doses of chemo/radiotherapy. The use of those high dose conditionings is restricted to young patients (< 55 years of age) without significant comorbidities. Unfortunately, median patient age at diagnosis of most haematological malignancies ranges from 60 to 70 years. It has been accepted since the late 1970s that the occurrence of acute and/or chronic graft-versus-host disease (a life-threatening complication of allogeneic transplantation consisting of host organ destruction by donor T cells present in the graft) leads to a dramatic decreased risk of relapse thanks to the destruction of host tumour cells by donor T cells (graft-versus-tumour effects). These observations led several groups of investigators to develop non-myeloablative conditionings for allogeneic haematopoietic stem cell transplantation (also termed mini-transplant) based nearly exclusively on graft-versus-tumour effects for tumour eradication. After a brief introduction, this article reviews preliminary results of nonmyeloablative transplantation and then present some perspectives aimed at increasing the efficacy while decreasing the toxicity of this approach.

摘要

异基因造血干细胞移植是许多严重血液疾病患者的最佳治疗选择。异基因移植通常先进行由高剂量化疗/放疗组成的清髓预处理方案。这些高剂量预处理的使用仅限于年龄小于55岁且无明显合并症的年轻患者。不幸的是,大多数血液系统恶性肿瘤患者的诊断中位年龄在60至70岁之间。自20世纪70年代末以来,人们已经认识到急性和/或慢性移植物抗宿主病(异基因移植的一种危及生命的并发症,由移植物中存在的供体T细胞破坏宿主器官组成)的发生会由于供体T细胞破坏宿主肿瘤细胞(移植物抗肿瘤效应)而导致复发风险显著降低。这些观察结果促使几组研究人员开发用于异基因造血干细胞移植的非清髓预处理方案(也称为小移植),几乎完全基于移植物抗肿瘤效应来根除肿瘤。在简要介绍之后,本文回顾了非清髓移植的初步结果,然后提出了一些旨在提高这种方法的疗效同时降低其毒性的观点。

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