The answers we still need from HSCT research

Friday 24 June 2022

Researchers have published a new article in the British Medical Journal reviewing the research on HSCT and MS.

The team included two consultant neurologists and a consultant haematologist from Sheffield University and Cambridge University. They looked through big databases of research studies and asked their international colleagues about new trials. They found questions about HSCT and MS still need answering. But new trials are exploring some of these.

Right now, the researchers suggest anyone considering HSCT seeks advice from their neurologist. And they've said, ideally, people should receive HSCT in a clinical trial. To make sure the risks are as low as possible, doctors should assess whether people are fit and healthy enough to cope with HSCT. And they should tell people about the risks and the 'uncertain benefits' of HSCT.

Read the full article in the British Medical Journal

Why did they do this review?

The article is part of a series called ‘Uncertainties’, which explores topics where research evidence isn’t completely clear yet.

There’s still uncertainty about how HSCT compares to other disease modifying therapies (DMTs). Some current DMTs can slow the damage MS causes in active MS. Two years after taking a highly effective DMT, 34-48% of people with relapsing MS experience no relapses, MRI activity or disability progression. The researchers say it’s not yet clear how HSCT compares to this.  

The review focuses on relapsing remitting MS because few DMTs are licensed for progressive MS. And no current trials are investigating HSCT for progressive MS. The researchers say studies are needed in this area too.

Why do the researchers think there's uncertainty about HSCT and MS? 


The researchers looked at the quality of evidence the key studies provide about how well HSCT works for MS.

Only one study, the MIST trial, provided moderate-to-high quality evidence. This was a phase 3 randomised controlled trial (RCT). RCTs are the gold standard for getting robust, reliable evidence about how well a treatment works.

After two years in the trial, only 1.92% of people in the HSCT group had progressed. But 54.5% of people in the DMT group had progressed. 110 people took part. Everyone had highly active relapsing MS despite taking DMTs.

The trial did follow some people for a longer period of time. But the researchers say the data wasn't robust enough to discuss in the article.

The researchers say this trial leaves us with uncertainty. This is because it didn’t compare HSCT with the current, most effective DMTs like alemtuzumab, ocrelizumab, cladribine and ofatumumab. So we don’t yet know which is more effective.

Other types of study have reported 61-92% of people not experiencing relapses, disability progression or MRI activity for two years after HSCT. But the researchers say these studies "do not provide robust evidence" because of their size or design. For example, some of these trials didn’t compare HSCT with a control group (people who didn’t have HSCT).


Side effects soon after HSCT are common. For example, fever or diarrhoea. And sometimes people can experience these very severely.

But deaths related to HSCT have reduced over the years. Studies have reported between 0.3 and 0.7% of people who've died as a direct effect of the treatment since around 2005. And a study looking at people in one hospital in the US found only 1 out of 507 people there died (0.19%). No one in the MIST trial died or had a severe reaction.

The researchers say we don’t yet know how the risks of HSCT compare to highly effective DMTs.

Different types of HSCT

There haven’t been any trials directly comparing different approaches to HSCT.

There are several ways of doing HSCT. And they differ in intensity. For example, some completely wipe out the immune system and others only wipe out parts of it.

Currently, there’s no evidence the highest intensity approaches are more effective. And they do come with greater risks.

European guidelines recommend intermediate intensity HSCT. This is what’s done in the UK.

What research will help with this uncertainty?

The researchers say we need more research to solve this uncertainty. This includes answering how effective HSCT is compared to newer, highly-effective DMTs at:

  • reducing relapses
  • halting disability progression
  • stabilising MRI activity.

Five new RCTs addressing this question have started or are planned. These include StarMS, RAM-MS and BEAT-MS.

Other questions researchers say need exploring include:

  • How safe is HSCT in the short and long-term for people with MS?
  • How does different intensity HSCT compare in effectiveness and safety?
  • How cost-effective is HSCT compared with current treatments?

Find out more about HSCT and other DMTs