Autologous haematopoietic stem cell transplantation (AHSCT) was initially approved for the treatment of haematological malignancies. However, since the 1990s, this approach has also been used in the treatment of severe autoimmune diseases, including MS, systemic sclerosis and Crohn’s disease . Clinical experience has revealed the ability of this treatment approach to halt inflammation and disease activity , preventing the recurrence of neuroinflammatory symptoms .
Several presentations at ECTRIMS 2022  explored aspects of this treatment modality in more detail, including optimal conditioning regimens and transplant protocols. There was also much interest around the use of AHSCT at the 37th congress of ECTRIMS in 2021, and the 9th ECTRIMS Focused Workshop in March 2022  focused on the latest evidence underlying the role of AHSCT in individuals in MS. A Therapy Session based on this workshop was held at the recent ECTRIMS congress  and concluded that AHSCT should be offered to all patients with highly active relapsing-remitting MS who have failed disease-modifying therapies, and to treatment-naïve patients with aggressive MS. In this ECTRIMS Insights article, we will examine some of the new data and meta-analyses that have been recently published with the aim of furthering our knowledge around the use of AHSCT in MS.
Evidence underlying the use of AHSCT in MS
In 2016, two retrospective reviews were published examining the first 20 years of experience with the use of AHSCT in individuals with MS. At that time, it was estimated that over 2000 individuals  had received AHSCT for severe autoimmune disease, with the majority being patients with MS. Approximately one-third of individuals receiving AHSCT experienced a complete response, which proved to be durable. It was noted that the safety profile of AHSCT had improved over time , with careful selection of patients required to optimise outcomes. It was suggested that the ideal candidate for AHSCT would be a young patient, with a short disease duration, with recurring and disabling relapses and the presence of inflammatory activity on brain magnetic resonance scans, who had been found to be unresponsive to approved therapies.
At the present time, few randomised clinical trials  fully exploring the potential benefits of AHSCT in individuals with MS have been completed, and the available evidence mainly consists of non-randomised, uncontrolled clinical trials or data from retrospective or observational cohorts. However, a number of important randomised clinical trials are planned or ongoing. Initial studies in MS focussed on the treatment of individuals with progressive disease at onset, with AHSCT considered an ‘end of line’ treatment. However, the majority of subsequent trials have recruited younger patients with relapsing-remitting MS (RRMS), who don’t have significant disability as measured by the EDSS (Expanded Disability Status Scale) . Limited evidence from two small randomised controlled trials has demonstrated that AHSCT may slow disease activity and disability progression  in some patients. However, how this observed efficacy compares with newer, highly effective disease modifying therapies (DMT) is still the subject of ongoing investigation.
Updated guidelines issued by the European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and the International Society for Cell & Gene Therapy (ISCT) (JACIE)  in 2020 support the use of AHSCT in RRMS, but also note that comparative, controlled trials with DMTs are required to fully assess the benefits of this treatment approach.
A recently published systematic review and meta-analysis  aimed to provide a comprehensive overview of the safety and efficacy of AHSCT in individuals with MS. Overall, 50 studies involving a total of 4831 patients with MS were included in this analysis, which demonstrated a significant decrease in EDSS score and a significant reduction in relapse rate among individuals who had received AHSCT. Moreover, the pooled estimate of progression-free survival following AHSCT was 73% (95% confidence interval [CI] 69%, 77), overall survival was 94% (95% CI 91%, 96%), and 81% of patients with MS who received AHSCT remained relapse-free (95% CI 76%, 86%). Based on these findings, the authors concluding that AHSCT is highly effective at preventing disease progression and relapse, in addition to reducing inflammatory responses and associated central nervous system (CNS) lesions in individuals with MS.
Conditioning regimens and treatment protocols
The conditioning regimens used prior to AHSCT in MS are variable, with both high- and intermediate-intensity regimens being investigated . At present, there is no strong evidence base for the routine use of high-intensity conditioning regimens , particularly given the associated mortality risks. In contrast, outcomes following the use of intermediate-intensity conditioning regimens have shown encouraging efficacy in terms of relapse and disease progression, making their use far more attractive. The most recent treatment protocols for AHSCT in individuals with MS have been published by groups in Ottawa  and Mexico , both of which aim to improve outcomes and minimise toxicity for individuals undergoing treatment. Moreover, a study conducted by Burt and colleagues  demonstrated the superiority of a non-myeloablative conditioning regimen followed by AHSCT in patients with MS. A further single centre study by the same group  has demonstrated a 5-year progression-free survival of 95% and a 5-year overall survival of 98% in individuals with relapsing-remitting MS treated using this protocol. As knowledge increases, it will be interesting to see what further improvements to conditioning regimens may be made.
Promoting continued advances in research
ECTRIMS welcomes this increased knowledge around the potential use of stem cell transplantation in the treatment of individuals with severe MS and applauds the efforts of the scientific community to constantly improve our understanding of this important treatment modality. We remain optimistic that ongoing research will continue to improve our knowledge of how best to treat individuals with all types of MS.
ECTRIMS Insights articles are produced with an intent of being a neutral source of information sharing and objective analysis for the MS and neuroscience community. Unless otherwise stated, cited information in our articles does equivocate official endorsement from ECTRIMS.
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