目的:了解历史和当前MLD治疗的获益-风险情况。
方法:对有效性进行了系统评价,安全,MLD治疗的成本和成本:异基因造血干细胞移植(HSCT)和根据最佳实践进行的自动干细胞移植(arsa-cel)。
结果:从文献检索中检索到了6940篇标题和摘要,从其他来源检索了26篇。从这些,共选择了35份报告12项研究的手稿纳入审查。没有控制的多臂试验。然而,我们提供了两种介入治疗(alloHSCT和arsa-cel)与标准/支持治疗(自然史)的比较观察结果.对生存没有好处,接受alloHSCT的LI患者的粗大运动功能和认知功能,患者经历了与LI自然史相似的疾病进展。对于接受alloHSCT的青少年患者,与自然史相比,没有观察到生存率的差异,然而,据报道,一些患者(特别是症状前或症状轻微的LJ患者)的认知和运动功能稳定,而其他人则经历了疾病进展。此外,alloHSCT与严重并发症相关,如治疗相关死亡率,移植物抗宿主病,并在LI和EJ治疗的患者中再次移植。大多数接受arsa-cel治疗的LI和EJ患者似乎发育正常,保存,或者粗大运动功能和认知功能进展较慢,与自然史患者的快速下降相反。在LI患者中观察到Arsa-cel相对于自然史和alloHSCT的生存益处。与AlloHSCT相比,接受Arsa-cel治疗的LI和EJ患者具有更好的粗大运动功能和认知功能,对运动和认知能力下降的影响有限。没有关于LJ患者的arsa-cel治疗的数据报道。
结论:总体而言,本系统综述表明,与NHx和HSCT相比,通过保留大多数患者的认知功能和运动发育,在LI和EJMLD患者中使用arsa-cel治疗可获得临床相关益处,并增加LI患者的生存率。然而,需要进一步的研究来证实这些发现,鉴于它们是基于非RCT研究的结果。
To understand the benefit-risk profile for historical and current treatments for MLD.
A systematic review was conducted on the effectiveness, safety, and costs of MLD treatments: allogeneic haematopoietic stem cell transplantation (HSCT) and atidarsagene autotemcel (arsa-cel) according to best practice.
A total of 6940 titles and abstracts were retrieved from the literature searches and 26 from other sources. From these, 35 manuscripts reporting on a total of 12 studies were selected for inclusion in the review. There were no controlled multi-armed trials. However, we provide observations comparing two interventional therapies (alloHSCT and arsa-cel) and each of these to standard/supportive care (natural history). There were no benefits for survival, gross motor function and cognitive function for LI patients receiving alloHSCT, as patients experienced disease progression similar to LI natural history. For juvenile patients receiving alloHSCT, no differences in survival were observed versus natural history, however stabilisation of cognitive and motor function were reported for some patients (particularly for pre- or minimally-symptomatic LJ patients), while others experienced disease progression. Furthermore, alloHSCT was associated with severe complications such as treatment-related mortality, graft versus host disease, and re-transplantation in both LI and EJ treated patients. Most LI and EJ patients treated with arsa-cel appeared to have normal development, preservation, or slower progression of gross motor function and cognitive function, in contrast to the rapid decline observed in natural history patients. A survival benefit for arsa-cel versus natural history and versus alloHSCT was observed in LI patients.LI and EJ patients treated with arsa-cel had better gross motor function and cognitive function compared to alloHSCT, which had limited effect on motor and cognitive decline. No data has been reported for arsa-cel treatment of LJ patients.
Overall, this systematic review indicates that compared to NHx and HSCT, treatment with arsa-cel results in clinically relevant benefits in LI and EJ MLD patients by preserving cognitive function and motor development in most patients, and increased survival for LI patients. Nevertheless, further research is required to confirm these findings, given they are based on results from non-RCT studies.