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Stem cell therapy: Balancing hope and hype

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Stem cell therapy

Last year a Panorama programme on stem cell therapy in MS brought this experimental treatment to national attention. One year on, we spoke to Professor John Snowden, whose work was featured in the programme, and Dr Eli Silber, who is part of the London MS stem cell group, about how stem cell treatment is becoming available, who might benefit and the risks to be aware of

Professor Snowden is Consultant Haematologist at Sheffield Teaching Hospitals. His work was featured in the Panorama programme on stem cell treatment in January 2016

I’ve been working in haematology and stem cell treatment for 20 years, but it’s only really in the last few years that people with MS have started to be treated in the UK. The enthusiasm has started to pick up among the neurology community. But the stem cell label is used very freely and sometimes it can have a negative impact. I want to clear up some of the confusion. 

There’s lots of different types of terminology around bone marrow transplants, but there’s one unifying term – haematopoietic stem cell transplantation (HSCT).

So what exactly is HSCT? It’s a procedure whereby we collect bone marrow cells from the person to be treated, we administer chemotherapy or radiotherapy (or both) to wipe out the immune system, and then the harvested cells are transfused back into the person to reboot the immune system, hopefully without the autoimmune effects of MS. This is called an autologous transplant, which means that we use cells from the patient themselves rather than from a donor. We do this all the time for myeloma and lymphoma, and now we’re increasingly using it in MS.

There are various intensities of HSCT treatment, depending on what we’re treating. In MS we do the low-risk type of transplant. Treatment-related mortality for all of autologous transplants – including myeloma and lymphoma, often people who are older and less healthy – at Sheffield is about 1%. We do 100 of these transplants a year. A very small number of them are MS patients. But we’ve had no deaths in MS. 

In contrast, the high-risk transplants have a treatment-related mortality of 10-30%, three years after treatment. That’s a gargantuan risk, but it’s justified if the leukemia (for example) is going to kill the patient. In that situation we make the patients aware of the risk, and they accept it. But it’s not appropriate to take that kind of risk in MS. 

It’s a complex process. It’s not a drug that you have to use on a licence. If HSCT had been a drug, it might have moved much more quickly to become more widely available. But there’s not a lot of vested interest or corporate support – it’s been academia that’s moved it on.

There are still relatively few people with MS treated with HSCT, but it’s increasing. Transplant in autoimmune diseases is not new. It’s taken a long time to come through. It’s about four decades old. The first animal models were done in the 1970s and 80s. We’ve also had patients with leukemia, who happen to also have MS, and after HSCT both conditions had been made better.

It wasn’t until 1995 that the first patients with MS were treated with autologous HSCT. Shortly after that the European Society for Blood and Marrow Transplantation (EBMT) set up an autoimmune diseases working party and created guidelines and a database. One of the strengths of transplantation is that every transplant in Europe and the UK is entered in the database, which now contains over 2000 patients with autoimmune diseases. 

There have now been around 1000 MS stem cell transplants in Europe, and probably another 1000 in the US. There’s been a gradual increase since 1995 through to 2016. Around 120 patients have received this treatment in 2015. 

It became clear early on that HSCT was effective on the inflammatory activity in relapsing remitting MS (RRMS). One trial looked at 21 people with MS and compared stem cell transplants versus another style of chemotherapy. They found that transplants significantly reduced lesions, and also reduced relapses. But the trial was too short to show any improvement in disability. 

A more recent study of people with RRMS in Chicago suggests that EDSS scores fell by an average of a point, and there was a four-year relapse-free survival of 87%. There were no mortalities. Retrospective data from Sweden, using a slightly different regimen, found progression-free survival of 80%. 

There’s a big question over how hard we should treat people. A small recent study tried to reduce the intensity of the chemotherapy and the results weren’t so good. There were more relapses. So we have to find the sweet spot. If you go high you might get some good results, as in the Canadian study this year which found no MS activity and reduced brain atrophy post-HSCT, but they had one treatment-related death and another serious complication. So for me this treatment is too hard, too tough. 

We also need to look at the cost effectiveness. There are some good drugs in MS but they are all expensive. In our centre HSCT costs around £30,000. It’s a one-off. That could be a game changer if we can show transplant is efficacious while being safe. 

But we still need strong evidence from trials. At Sheffield we’ve been involved in a trial that’s being led from Chicago, and also involves centres in Sweden and Brazil. That should report in a year. It compares HSCT vs standard MS drugs, but doesn’t include alemtuzumab, which is widely seen as the most potent current MS drug. But the trial might provide proof of principle, and demonstrate that HSCT can challenge other treatments. 

Dr Eli Silber is a consultant neurologist at Kings College Hospital and a member of the London HSCT group

We set up the London MS HSCT group because we wanted to improve the way that people with MS were being selected for treatment, who selected them and how they were followed up. 

Through a lot of effort we’ve pulled together a group to create shared guidelines about who should be treated, making sure they’re seen within a multidisciplinary team and are supported in hospital by both the haematology and neurology departments, and are appropriately followed up. 

We want to make sure that if we are offering HSCT, we gather the relevant date and do appropriate follow-up for audit. These are vulnerable people and every one of them needs to be involved in the research.

Within the London MS group we are all keen on offering this therapy to appropriate patients, I am quite cautious with respect to HSCT. I tend to explain to patients why they should or shouldn’t be treated. If we think someone should be treated, I will strongly support them in this. But if I think someone shouldn’t be treated I will tell them so. 

Lots of people are now requesting HSCT. There’s a hope that it is a regenerative medicine. People are desperate for something to regrow their nervous system. We need to tell them that’s not the case with what’s on offer at the moment. 

These days we hear of lots of people travelling abroad for stem cell treatment. The people doing this treatment aren’t in touch with the neurology teams in the UK. We don’t know if they are offering the treatment to appropriate people. And they aren’t arranging the follow-up that people need after the treatment. People often come back with a letter to their GP. We have to pick up the pieces and re-engage them with neurology teams and haematology teams because we have a duty of care, but it puts us in a difficult position.

We need to make sure that people are aware of charlatans. I am concerned that it may be a business built on hype.

Neurologists tend to be much more cautious than haematologists. Because haematologists are often treating life-or-death conditions like cancer, they have accepted a certain level of mortality. But MS patients tend not to die, or if they do, it tends to be after many years, due to complications. So we tend to be much less tolerant of these risks. 

What are the minimum standards we should expect from a treatment that is expensive, aggressive, has a significant mortality rate and a high morbidity? 

•  It should be able to perform consistently better than available therapies. 

•  It should be available to a reasonable proportion of the population – not just in a small number of centres. 

•  We need to make sure that it’s more beneficial than existing therapies. 

In the London group we say that people will only be treated if they have rapidly evolving relapsing remitting MS and have failed to respond to a potent therapy. Or if they have very aggressive primary progressive disease with evidence of ongoing disease activity. 

HSCT appears to be effective if it’s chosen well and if the patients are well looked after. But you need to choose the patients well. In London we’ve treated 30 people over about 4 years. It’s a cautious approach. It’s still not a treatment that’s suitable for the vast majority of our patients.

Treatment on the NHS is considered for people meeting the eligibility criteria at Royal Hallamshire Hospital, Sheffield, and the London MS-AHSCT Collaborative Group at King's College Hospital. If you feel you may be suitable for treatment, you need to speak to your neurologist or GP about being referred. The MS Trust has provided funding for crucial stem cell research in Bristol. We're also auditing the existing London stem cell service to understand how we can develop safe, high quality services for the future.