Gratwohl A, Passweg J, Gerber I, Tyndall A
Division of Haematology, Department of Internal Medicine, Kantonsspital Basel, Switzerland.
Best Pract Res Clin Haematol. 2001 Dec;14(4):755-76. doi: 10.1053/beha.2001.0171.
Much progress has been made in the field of haemopoietic stem cell transplants (HSCTs) for severe autoimmune disorders. Theoretical considerations, animal data and anecdotal evidence suggested some time ago that intensive immunoablation followed by autologous HSCT could restore normal immune reactivity in patients with severe autoimmune disorders. Based on a concept statement issued in 1995, two European societies, the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT) began collecting phase I/II trial data in an international collaborative network. Sufficient information from more than 350 patients allows a preliminary assessment with level three evidence. Autologous HSCTs can induce remissions in all disease categories tested so far. Remissions can be transient or durable. HSCTs are associated with significant morbidity and mortality. Treatment-related mortality (TRM) is near 10% at 1 year and is associated with the intensity of the conditioning and the stage of the disease at the time of transplant. Marked interdisease differences exist. There are few data available in haematological autoimmune diseases, more in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA) and multiple sclerosis (MS). Patient selection has been recognized as a crucial element from the phase I-II trials. Patients with advanced disease, severely compromised organ function or irreversible organ damage should not be considered as candidates for HSCT. Prospective randomized studies should now determine the value of HSCT compared to standard therapy. Such trials are ongoing for patients with systemic sclerosis (ASTIS trial--Autologous Stem Cell Transplantation International Scleroderma Trial) or are planned for patients with multiple sclerosis (ASTIMS trial--Autologous Stem Cell Transplantation International Multiple Sclerosis Trial) and rheumatoid arthritis (ASTIRA trial--Autologous Stem Cell Transplantation International Rheumatoid Arthritis Trial). More phase II data are needed for other indications such as SLE and JIA.
在用于治疗严重自身免疫性疾病的造血干细胞移植（HSCT）领域已经取得了很大进展。一段时间以前，理论思考、动物实验数据和轶事证据表明，在进行自体HSCT之前先进行强化免疫消融，可能会使患有严重自身免疫性疾病的患者恢复正常免疫反应性。基于1995年发布的一份概念声明，两个欧洲学会，即欧洲抗风湿病联盟（EULAR）和欧洲血液与骨髓移植组（EBMT）开始在一个国际协作网络中收集I/II期试验数据。来自350多名患者的充分信息使得能够以三级证据进行初步评估。自体HSCT可以在目前所测试的所有疾病类别中诱导缓解。缓解可以是短暂的或持久的。HSCT与显著的发病率和死亡率相关。治疗相关死亡率（TRM）在1年时接近10%并且与预处理的强度以及移植时疾病的阶段有关。疾病之间存在明显差异。血液系统自身免疫性疾病的可用数据很少，系统性硬化症（SSc）、系统性红斑狼疮（SLE）、幼年特发性关节炎（JIA）和多发性硬化症（MS）的数据较多。从I-II期试验开始，患者选择就被认为是一个关键因素。患有晚期疾病、器官功能严重受损或器官有不可逆损伤的患者不应被视为HSCT的候选者。现在前瞻性随机研究应该确定HSCT与标准治疗相比的价值。此类试验正在系统性硬化症患者中进行（ASTIS试验——国际硬皮病自体干细胞移植试验），或者计划在多发性硬化症患者（ASTIMS试验——国际多发性硬化症自体干细胞移植试验）和类风湿性关节炎患者中进行（ASTIRA试验——国际类风湿性关节炎自体干细胞移植试验）。对于其他适应症如SLE和JIA，还需要更多的II期数据。
