Department of Rheumatology, University of Basel, Basel, Switzerland.
, Im Erlisacker 14, 4103, Bottmingen, Switzerland.
BioDrugs. 2019 Aug;33(4):401-409. doi: 10.1007/s40259-019-00364-3.
Three prospective controlled clinical trials and numerous small series and case reports have confirmed that durable, drug-free remission in systemic sclerosis is possible via an autologous hematopoietic stem cell transplantation. Similar results have been seen in other autoimmune diseases. The exact mechanism by which this immune "reset" was achieved in some but not all cases remains elusive, but includes major reduction of autoreactive immune competent cells, re-establishment of T- and B cell regulatory networks and normalization of tissue niche function, particularly vascular. Some aspects regarding mobilization, conditioning and graft manipulation still remain open, but clearly a significant toxicity is associated with all effective regimens at present, and therefore patient selection remains a key issue. In the hematology/oncology arena, major efforts are being made to reduce genotoxic and other collateral toxicity induced by current mobilization and conditioning protocols, which may also translate to autoimmune disease. These include developments in rapid mobilization and antibody drug conjugate conditioning technology. If effective, such low-toxicity regimens might be applied to autoimmune disease at an earlier stage before chronicity of autoimmunity has been established, thus changing the therapeutic paradigm.
三项前瞻性对照临床试验以及众多小系列和病例报告已经证实，通过自体造血干细胞移植可以使系统性硬化症获得持久、无药物缓解。其他自身免疫性疾病也观察到了类似的结果。尽管在某些但不是所有情况下都实现了这种免疫“重置”的确切机制仍不清楚，但包括自身反应性免疫细胞的大量减少、T 细胞和 B 细胞调节网络的重建以及组织龛功能（特别是血管）的正常化。关于动员、预处理和移植物处理的一些方面仍然存在争议，但目前所有有效方案都与明显的毒性相关，因此患者选择仍然是一个关键问题。在血液学/肿瘤学领域，正在努力减少当前动员和预处理方案引起的遗传毒性和其他副作用，这也可能转化为自身免疫性疾病。这些包括快速动员和抗体药物偶联物预处理技术的发展。如果有效，这种低毒性方案可能会在自身免疫性疾病的慢性期之前更早地应用于自身免疫性疾病，从而改变治疗模式。
