- This large multinational study found AHSCT was better at reducing relapses than the disease-modifying treatments (DMTs) cladribine and alemtuzumab.
- Future studies are needed to investigate whether the benefits of AHSCT are long-lasting.
- AHSCT is not for everyone and people with MS should discuss with their neurologist whether AHSCT is right for them.
What is AHSCT?
Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment for MS that aims to “re-boot” the malfunctioning immune cells in MS. It replaces them with immune cells that are less reactive and less likely to continue attacking the body and cause relapses. AHSCT is not able to repair myelin and nerves that are already damaged.
AHSCT involves a pre-treatment to make a person’s bone marrow release blood stem cells into the blood. These stem cells are collected and frozen in the laboratory while the individual is given chemotherapy (also called a conditioning regimen) to remove or partially remove their immune system. Then the stem cells are thawed and returned to the individual by infusion into the veins. After that, the person is given supportive care as their immune system rebuilds.
There is a lot of interest in how treatment with AHSCT compares to other immunosuppressive medications for MS. So far, there have been no clinical trials that directly compared the effectiveness of AHSCT to the DMTs cladribine and alemtuzumab, or other types of studies that compared AHSCT to cladribine. Studies that have compared AHSCT to alemtuzumab have had limitations and mixed conclusions.
What did the researchers do?
A multinational group of researchers, including researchers supported by MS Australia, compared data from people with relapsing remitting MS treated with AHSCT to those who had received cladribine or alemtuzumab. Data were collected from 2006 to 2023 from seven specialist centres and the international MSBase registry.
The researchers used statistical methods to mimic a clinical trial that directly compared AHSCT to cladribine and AHSCT to alemtuzumab. To make sure the comparisons were fair, study participants were matched on a range of characteristics, including sex, age, disability, number of relapses before baseline, time since first MS symptom, the most effective DMT used before the study, and geographical region.
The relapse rates and disability levels were compared across the groups. Disability was measured using the Expanded Disability Status Scale (EDSS) and confirmed by subsequent EDSS scores over at least six months.
The researchers followed participants for up to five years.
What did the researchers find?
Published in the journal Brain the study included 163 people who received AHSCT, 562 who were treated with cladribine and 283 who were treated with alemtuzumab.
The results showed that AHSCT was more effective in reducing relapses than cladribine or alemtuzumab. People who received AHSCT had a relapse rate which was one-third that of people who had received cladribine and about half that of people who had received alemtuzumab. Also, people treated with AHSCT were 76% less likely to experience a relapse than people treated with cladribine and were about half as likely to experience a relapse compared to those treated with alemtuzumab.
AHSCT was associated with greater disability improvement compared to either cladribine or alemtuzumab. People who were treated with AHSCT were 2.2 times as likely to experience disability improvement compared to people treated with cladribine and twice as likely compared to those treated with alemtuzumab. But people treated with AHSCT had a similar risk of disability worsening to those treated with either DMT throughout the follow-up period (three years for cladribine and five years for alemtuzumab).
The safety profile of AHSCT in this study was similar to that in other reports and there were no treatment-related deaths. The researchers were not able to compare the safety of AHSCT with that of the two DMTs.
What does this mean for people with MS?
Overall, AHSCT prevented more relapses than cladribine or alemtuzumab and was associated with greater disability improvement. But there were no differences between AHSCT and the two DMTs in the risk of disability worsening.
The only published clinical trial that directly compared AHSCT to other DMTs (the MIST trial) did not compare AHSCT to alemtuzumab or cladribine. Currently, there are four clinical trials underway (RAM-MS, STAR-MS, BEAT-MS and NET-MS) that are comparing AHSCT to several DMTs – including alemtuzumab and cladribine – with results expected over the next five years.
By including a large number of participants and matching them for their baseline characteristics, this study contributes strong evidence that AHSCT is more effective in reducing relapses compared with alemtuzumab and cladribine. But as follow-up was only three to five years, more studies are needed to find out whether the benefits of AHSCT are long-lasting, to help people with MS make informed decisions about whether this treatment is suitable for them.
AHSCT does have serious risks. The conditioning regimens strongly suppress the immune system, leading to a high risk of infection and bleeding disorders. The risk of death with AHSCT has decreased in recent years, likely because of improved conditioning regimens and better supportive care following transplantation. There have been no transplant-related deaths recorded at the Australian centres that provide AHSCT to people with MS.
People with MS considering AHSCT are advised to discuss with their neurologist whether the treatment is right for them.
For more information about AHSCT, please click here.
See MS Australia’s updated Position Statement about AHSCT here.
Anyone who has received AHSCT or who is considering treatment with AHSCT is encouraged to contribute their information to the MS AHSCT Registry. More information can be found here.
