Stem cells and MS - AHSCT

Stem cells are part of the body’s normal repair system which replaces damaged or dying cells. Stem cells are unspecialised as they haven’t developed to carry out a particular function yet.

Each stem cell has the potential to develop into one of a number of different cell types depending on the body’s needs at a particular time, such as becoming a nerve cell, a red blood cell or a heart muscle cell. Once they’ve undergone this change they’re known as specialised cells and they can’t go on to change again.

The special properties of stem cells means that they have the potential to be used to treat a number of conditions, including multiple sclerosis. The most studied type of stem cell therapy for MS is autologous haematopoietic stem cell transplantation (often shortened to AHSCT, ASCT or HSCT). This uses your own stem cells, which are collected and then injected back into your body. Early results have been encouraging.

A small number of centres provide AHSCT on the NHS under specific circumstances to a very small number of people. People accepted for treatment generally either have a very aggressive type of MS or continue to have relapses even after trying one or more disease modifying drugs.

Introduction to stem cell treatment in multiple sclerosis

How does AHSCT work in MS?

Haematopoietic (pronounced hee-mato-poy-etic) stem cells are found mainly in our bone marrow, although small numbers circulate in our blood. They develop into the different types of blood cells including some cells which are part of the immune system. They’re produced in large numbers throughout our lives to continually replenish our blood and immune system as other cells die and are replaced.

The aim of AHSCT is to replace or reboot your body’s immune system so that it no longer attacks your myelin or causes inflammation in your brain and spinal cord. AHSCT uses high doses of chemotherapy to wipe out your existing immune system, which is then rebuilt using stem cells collected from your blood before you have the chemotherapy. The hope is that your rebooted immune system will stop attacking you and there will be no further damage.

Using your own stem cells minimises the risk of them being rejected by your body. If the stem cells come from someone else (a donor) it’s known as an allogeneic transplant – this is associated with a higher risk of complications than an autologous (self) transplant, so it’s not generally used for MS.

AHSCT results suggest that it can delay or halt further progression of your MS symptoms. Recent evidence for AHSCT comes from the international MIST study (Multiple Sclerosis International Stem Cell Transplant) which recruited 110 people with MS in Brazil, Sweden, the USA and the UK. The participants were randomly assigned either AHSCT or a standard DMD, and followed over the next few years to see whether their disability had worsened.

After one year, people who had been given AHSCT showed improvements in their disability scores (EDSS). In people given DMDs, their disability had increased. Significantly fewer people in the AHSCT group experienced disability progression than in the DMD group.

You can read more about the MIST trial results in our news article.

What does the AHSCT procedure actually involve?

There are six main stages to the procedure. The first five take place over several weeks, and the sixth stage can take up to a year.

Stage 1

The first stage is known as mobilisation. A combination of drugs are given via an infusion (drip) to encourage your stem cells to move from your bone marrow and into your blood stream so they can be collected. Mobilisation uses a chemotherapy drug (cyclophosphamide) and a synthetic form of a natural growth factor called G-CSF (granulocyte-colony stimulating factor). Your MS symptoms can get temporarily worse during this phase.

Stage 2

This stage involves the collecting (or harvesting) of your stem cells. It typically happens about 10 days after mobilisation, once blood tests have shown that there are enough stem cells present in your bloodstream. The process takes between half a day and one day. You are connected to a machine which collects your blood through a needle in your arm, separates out the stem cells and then returns all the other components of the blood to your body.

Stage 3

The third stage involves freezing (or cryopreserving) your harvested stem cells. This keeps them ready to be returned to your body at a later stage.

Stage 4

Stage four of the process is another round of chemotherapy, known as conditioning chemotherapy. This gets your body ready for the return of your stem cells. Conditioning chemotherapy aims to destroy the cells that are involved in MS disease activity from inside your bone marrow and blood stream. There are two options here; either a complete, high intensity chemotherapy (myeloablative chemotherapy) or a lower intensity chemotherapy that partially eliminates the immune cells (non-myeloablative chemotherapy). More recent procedures have tended to use the less aggressive lower intensity chemotherapy method.

This stage usually takes several days and you may need to take drugs to control any nausea and vomiting which are common side effects of the chemotherapy. You may also be given steroids to dampen down any immune reactions.

Stage 5

The fifth stage is transplantation, also known as stem cell return. This is where your stored stem cells are thawed and returned to your blood by infusion (through a drip). Transplantation often takes place a couple of days after the conditioning chemotherapy and will only be done once all the chemotherapy drugs have cleared from your system. The process takes a 2-3 hours and is similar to having a blood transfusion. The stem cells make their way to your bone marrow (engraftment) and should start making new blood and immune cells within 10 to 30 days. During that 10 to 30 day period, you have, in effect, no immune system and are highly vulnerable to infection.

Stage 6

The sixth and final stage is recovery. AHSCT is a complex, aggressive procedure and recovery can take a considerable length of time. You should expect to be off work for quite a while as typically you need three to six months to recuperate from the procedure. However, some people can take more than a year to recover.

If you wish to learn about the personal and emotional impact of the AHSCT procedure, then speaking to someone who has been through the process can be helpful. Support groups and video diaries, such as Chris Wasey's vlog can give you some extra insight.

Risks and side effects of AHSCT

There are several potential side effects both during and after AHSCT.

  • Immediately after the conditioning chemotherapy, you are highly susceptible to infection. This is also known as being immunocompromised. You will remain vulnerable until your immune system has been rebuilt by your stem cells following the transplantation stage. You should be closely monitored by your health professionals to make sure that you remain as well as possible and you are likely to be in an isolation room in hospital for several weeks. Both you and any visitors will need to take precautions to avoid introducing infections. What might normally be a low threat to your health can be very serious, even life threatening, during this period.
  • Previous infections that you have had can become active again. This is particularly common with the viruses that cause shingles, cold sores and herpes. You may be given antibiotics and transfusions to support you through this vulnerable time.
  • It’s possible to develop other autoimmune conditions, particularly autoimmune thyroiditis where the body sees the thyroid, and the hormones it produces, as threats and so attacks them. In the MIST study (outlined below) 4 people out of 83 given AHSCT developed thyroid problems after the treatment.
  • You may experience side effects from the chemotherapy, which can include fatigue, weakness and a temporary loss of appetite. You will be at an increased risk of bleeding and bruising and your MS symptoms may also be worse for some time. Hair loss is common but should only last between one and six months, although your hair may grow back a slightly different colour or texture. Other longer term side effects can include lowered fertility, or early menopause, if high dose chemotherapy has been used.
  • There is a risk of dying due to the procedure. Although treatment procedures are improving, clinical trials since 2001 have still had treatment-related death rates of one or two people in every 100 (1.3%), according to analysis by the European Group for Blood and Marrow Transplantation (EBMT). The majority of deaths were due to infections. However, looking at transplants carried out since 2005, the mortality rate has decreased further still to around 1 in 330 (0.3%). There were no deaths or life-changing adverse reactions reported in the MIST study, which was published in 2019.
  • The chemotherapy components of AHSCT are toxic to the ovaries and testicles, resulting in high levels of infertility. Patients are usually advised to bank sperm or eggs before undergoing stem cell treatment. This is a relatively straightforward process for men, but is more difficult and invasive for women. It can also be expensive in some parts of the UK, as the cost is not routinely covered by all Integrated Care Boards (ICBs).

Is AHSCT available for MS in the UK?

Scotland, Wales and England have all approved AHSCT for use with eligible people with MS. AHSCT for MS is available on the NHS at a small number of centres in England, but the number of people who are accepted for treatment is extremely small.

In the UK, any hospital performing transplants, including stem cell therapy, must be accredited by the Joint Accreditation Committee - ISCT & EBMT (JACIE). The transplant centre has to show that procedures are being carried out to agreed standards by suitably trained staff. Accredited centres are inspected regularly to make sure that these standards have been maintained.

The main centres offering treatment on the NHS are Sheffield Teaching Hospitals, the London MS-AHSCT collaborative group with small numbers of patients treated at the South West Transplant Centre in Plymouth. People are usually only accepted if they have a very aggressive form of MS, or if they continue to have relapses even after trying one or more of the disease modifying drugs. Each hospital will have its own specific eligibility criteria but they may follow the guidelines developed by the European Group for Blood and Bone Marrow Transplantation.

Based on the data from clinical trials, you’re more likely to respond to treatment, and therefore be suitable for AHSCT, if you meet the following general criteria:

  • you have relapsing MS or progressive MS with evidence of continuing inflammatory disease, for example, active lesions are seen on recent MRI scans
  • you are continuing to have relapses when on a disease modifying drug treatment (at least one drug tried – though some centres suggest that AHSCT should only be considered in people who have relapses even after treatment with Lemtrada (alemtuzumab) and/or Tysabri (natalizumab), or in whom these drugs cannot be considered)
  • you are early in your MS disease course before the onset of any significant irreversible disability. Disability is often measured using the EDSS scale. Exact requirements will vary but would typically require the ability to walk at least 100m with or without using a single walking aid and with or without resting (EDSS of 6 or below)
  • you are fit enough to undergo the treatment regimen.

In addition, people with very aggressive MS, who have developed severe disability in the previous year, may be accepted for AHSCT.

The MS Trust is working in conjunction with the London group to conduct the first ever audit of a real-world UK MS stem cell service run outside of a clinical trial. From this audit we hope to understand how people with MS can be assessed and selected for stem cell treatment on the NHS, and what is needed to develop safe, high quality services for the future. We will report on the results of the audit as soon as they become available.

Clinical trials

You may be able to access AHSCT by taking part in a clinical trial, although you may be selected for the control or alternative treatment group rather than the AHSCT group. You can check for any new trials on the Clinical Trials website using the search term “multiple sclerosis AND stem cells” and then using the map function to focus in to the UK.

For example, the Star-MS clinical trial will recruit nearly 200 participants at 19 research centres around the UK beginning in 2021.  The study will compare highly effective disease modifying drugs with AHSCT over a 24 month period.  Find out more on the Star-MS study website.

Private healthcare

A small number of centres offer stem cell treatment privately in the UK. According to the Sheffield Teaching Hospitals website, they have limited capacity for overseas patients and fee paying patients from outside England. To discuss this option you would need to contact their dedicated private patient team.

The HCA Healthcare UK chain have begun to offer AHSCT for MS and are following the EBMT and JACIE guidelines. Treatment takes place at University College Hospital and the London Bridge Hospital, both in London.

If you are considering AHSCT, whether through the NHS, a trial or privately, you would need to be referred by your usual neurologist or GP to the relevant haematologist and neurologist.

Dr Eli Silber explains who is most likely to benefit from stem cell treatment and the latest research that's happening in this area.

Treatment outside the UK

There are clinics around the world that are offering stem cell treatment for MS on a commercial basis. This is sometimes known as stem cell tourism. Some, but not all of the centres, are offering AHSCT. There are other forms of stem cell treatment being researched in MS, but the evidence for their benefit is not as well established as AHSCT, so if you are considering going abroad you need to check exactly what kind of treatment is being offered.

The standards set by JACIE (mentioned above) have been adopted in some other countries. You can see a list of JACIE accredited centres in the UK and abroad. Other countries may have their own standards, for example FACT in the USA.

We are aware that centres in Mexico, Russia and Israel are offering the AHSCT procedure to people with MS, including people with progressive MS. The cost of treatment varies widely but can range between £30,000 and £85,000. If you are considering going abroad, it will be important to find out:

  • exactly what kind of treatment is provided – is it AHSCT or something else?
  • whether the clinic is regulated to international standards
  • whether others have benefited from treatment at the clinic
  • what follow up is provided
  • how safety, side effects and the effectiveness of treatment are monitored over time
  • what is, and is not, included in the price quoted and what you will need to pay for in addition to flights and possibly hotel accommodation, for example whether there will be any additional medications that you have to pay for once you’re home. The risk of having additional costs may be high if you develop complications after the initial treatment.

It will also be essential to make sure that there will be proper follow up and support in place once you have returned to the UK.

Key considerations

When considering any treatment, it is vital to weigh up all the different factors, discuss your options with health professionals, family and friends before deciding what seems best for you as an individual. It is important to look critically at the risks and not only the hope that is offered.

Below is our list of suggested actions if you, or someone you care about, think that AHSCT may be an appropriate treatment option.

Get independent information

If you would like to know more about stem cell therapies, it is important to seek accurate, unbiased information from trusted sources. The MS charities and independent stem cell organisations, such as EuroStemCell, the International Society for Stem Cell Research and the European Society for Blood and Marrow Transplantation, are a good place to start for a balanced overview. Find out more about our factsheets and publications at the bottom of the page.

Seek the opinion of your MS specialist team

Consult your MS team as they know you and your MS well. If your relapses are not well controlled by a disease modifying drug, they may suggest that you try an alternative. In some circumstances, your MS team may agree that AHSCT is appropriate. You will need a referral from your neurologist to take part in some clinical trials or to attend most hospitals providing AHSCT. You may need to provide some evidence of your MS disease activity, such as a recent MRI scan, or your history of previous treatments.

Your MS team will remain involved with your longer term care once you have recovered from the AHSCT procedure and no longer need the involvement of the AHSCT multidisciplinary team.

Check the credentials of the team

Check that the hospital where you will be treated has experience of stem cell transplantation in people with MS as worldwide experience is limited to a few centres. Visit the websites of clinics offering treatment to understand exactly what they offer and to whom, the process you would need to go through, the cost and any follow up support that is available. You could ask the clinics for any information sheets and eligibility criteria. Treatment should include assessment by an MS specialist neurologist and a haematologist working together as part of an AHSCT multidisciplinary team. Treatment should be explained in a written “informed consent document” in a way that you can easily understand. You should have the opportunity to ask questions at all stages of the process.

Clinic websites will probably include personal stories but may only show you their most successful cases. You may be able to get a more accurate idea of success rates by asking on forums or groups, such as Facebook, although, inevitably, people are more likely to talk about successes than side effects, complications or failure. Some people with MS have blogged about their experiences of having stem cell therapy.

Balance the risks and benefits to your health

Stem cell therapy has the potential to bring significant benefits to some people with MS. Good progress is being made through clinical trials and the outcomes of treatment are improving as more is learned. However, as research is still at an early stage, stem cell therapy is not widely practised and the results of treatment for a particular person cannot be predicted. The risks should be very carefully considered, including the possibility of treatment-related death, and weighed up against the potential benefits.

Find out about after care

It is important to know what care will be available after your AHSCT treatment especially if you are considering going abroad. What support will be available if you experience complications or side effects? This should be outlined exactly so that you know what to expect and who to contact if you have any concerns.

Consider the costs

Treatment in a clinical trial should be free. In addition, a very small number of people are being accepted in the UK for treatment on the NHS. The quotes for treatment abroad vary widely. Before making any commitment, it is important to establish the full costs of treatment including assessment, tests, treatment and follow up appointments. You will need to budget for your travel and for hotel costs for anyone going with you. You may also need accommodation for yourself if you are discharged from hospital but don’t feel strong enough to travel home straight away, or if you develop complications and need to extend your stay.

It is important to be cautious as there have been examples in the past of unscrupulous people making a profit by offering worthless treatments to people with MS at very high costs. Some clinics did not even check whether a person had MS or not.

Find out more

Burt RK, et al.
Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis.
JAMA 2015;313(3):275-284.
Full article (link is external)
Holloman JP, et al.
The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis.
American Journal of Stem Cells 2013;2(2):95-107.
Full article (link is external)
Radaelli M, et al.
Autologous bone marrow transplantation for the treatment of multiple sclerosis.
Current Neurology and Neuroscience Reports 2014;14(9):478.
Summary (link is external)
Nash RA, et al.
High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS.
Neurology 2017;88(9):842-852.
Full article (link is external)
Muraro P, et al.
Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis.
JAMA Neurology 2017;74(4):459-469.
Summary (link is external)
Snowden JA, et al.
Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation.
Bone Marrow Transplant 2012;47(6):770-790.
Full article (link is external)
Muraro PA, et al.
Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis.
Nature Reviews Neurology 2017;13(7):391-405.
Full article (link is external)
Sarkar P, et al.
Cell therapy for multiple sclerosis.
CNS Drugs 2017;31(6):453-469.
Summary (link is external)
Cohen JA, et al.
Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis.
Multiple Sclerosis Journal 2017; Apr 1:1352458517703802. [Epub ahead of print]
Summary (link is external)
Burt RK, et al.
Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease-modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis. A randomized clinical trial.
JAMA 2019; 321: 165-174.
Summary (link is external)
Massarotti et al.
Menstrual cycle resumption and female fertility after autologous hematopoietic stem cell transplantation for multiple sclerosis.
Mult Scler. 2021 Mar 12;13524585211000616.
Summary (link is external)
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