Background

What does AHSCT mean?

AHSCT (sometimes referred to as HSCT or bone marrow transplant) stands for Autologous Haematopoietic Stem Cell Transplantation. Haematopoietic refers to the type of stem cells used in the treatment, which are found in the bone marrow and blood and make new blood and immune cells. Autologous means ‘from the same place/person’ as the stem cells used in the procedure are the person’s own.

What happens in AHSCT?

This treatment is primarily an immune supressing chemotherapy treatment. It is a one-off procedure involving a number of steps over the course of several weeks. Blood stem cells are collected from a person’s bone marrow or blood, chemotherapy is then used to eliminate or partially eliminate their immune system. The individuals own blood stem cells are reintroduced back into their body via infusion to help restore the immune system. The stem cells help to regenerate a ‘new’ immune system after the chemotherapy. Research suggests that the ’re-set’ immune system is less likely to attack the brain and spinal cord.

What are stem cells?

Stem cells are a type of cell that are capable of renewal and repair in the body. There are different types of stem cells that are found at different stages of development and life, that each do different jobs.

  • Embryonic stem cells are found in the early stages of embryo development and are like a ‘blank slate’ – they can turn into any type of cell needed to make up all the tissues needed in the whole body.
  • Adult stem cells are found in later stages of life, but are in the human body before a person becomes “an adult”. They can be found in most organs and tissues in the body. These stem cells are already partly ‘programmed’ to turn into a particular type of tissue or cell. For example, skin stem cells are found in skin and help to renew and repair our skin. Mesenchymal stem cells are an example of a type of adult stem cell which can be found in fat tissue, umbilical cord and bone marrow.
  • Blood stem cells (haematopoietic stem cells) are found in the bone marrow and blood. It is a type of adult stem cell that is pre-programmed to generate new blood and immune cells.
  • Neural stem cells are found in the brain and spinal cord and are able to form nerve cells and support cells of the brain and spinal cord.

Does AHSCT repair damaged nerves?

There is no evidence to date to suggest that AHSCT can repair nerve fibres and the international studies suggest that there is unlikely to be reversal of more longstanding disability following AHSCT. The blood stem cells are a type of adult stem cell that is pre-programmed to become blood and immune cells. Following a round of chemotherapy, these stem cells are reinfused to speed up the recovery of the immune system. These stem cells do not contribute to repairing the damaged nerves but instead help to regenerate a new immune system that it is less likely to attack the brain and spinal cord. International studies have suggested that some people with MS may experience some reversal of disability following AHSCT, however, this is thought to be primarily as a result of normal repair of myelin around intact nerves that can occur once the inflammatory attack in the brain and spinal cord is suppressed.

How is AHSCT different to other types of stem cell treatments?

AHSCT is primarily an immune-suppressing chemotherapy treatment which aims to regenerate a new immune system that it is less likely to attack the brain and spinal cord. Other types of stem cells may hold potential to grow or repair tissue in areas of the brain and spinal cord that have been damaged or destroyed. However the use of these other types of stem cells in MS is still in the early stages of basic laboratory research, and is not yet used as a treatment for people with MS.

Some private clinics are offering forms of stem cell therapy for MS and other diseases which claim to successfully regrow damaged tissue using, for example, mesenchymal stem cells (see definition above) from fatty tissue, however clinical data on these therapies are currently lacking. These approaches are very different to AHSCT, which aims to regenerate the immune system. The NHMRC have released a fact sheet explaining the different types of stem cell treatments.

Procedure, effectiveness and safety

How long does the treatment take and how will it make me feel?

The one-off treatment involves several steps received over the course of one to two months:

Step 1: Administer pre-treatment to release blood stem cells from the bone marrow into the bloodstream – depending on the protocol used by the treating centre, this may include a lower dose of a chemotherapy agent such as cyclophosphamide infused over 1 to 2 days (this may cause nausea, fatigue, feeling unwell), as well as daily injections of a drug known as granulocyte colony stimulating factor (GCSF) for up to 10 days.

Step 2: A blood collection needle is used to take a blood sample from the vein. This blood sample will contain the blood stem cells.

Step 3: Freeze the blood stem cells – as the cells are frozen, they can be stored for some time. Steps 1-3 can happen at any time, weeks or months prior to the chemotherapy step (step 4), however, this is usually done around 2-4 weeks prior to receiving chemotherapy.

Step 4: Administer chemotherapy to remove or partially remove the immune system. Depending on the chemotherapy protocol in use, the timing and side-effects may be different. However, it will generally involve an intravenous infusion of chemotherapy agents over approximately 5 days. This will be associated with symptoms such as nausea, fever, hair loss (in the longer term) and fatigue.

Step 5: Return thawed blood stem cells by infusioninto the vein (this is done immediately following the course of chemotherapy) This would be a relatively brief infusion and is unlikely to cause additional symptoms, but the effects of the chemotherapy may continue.

Step 6: Supportive medical treatment while the immune system rebuilds – From the beginning of the chemotherapy step and for several weeks afterwards patients will require careful monitoring and additional treatments. As the chemotherapy also affects blood platelets as well as the immune system, the patient may require blood transfusions to prevent bleeding. The immune system is also severely suppressed so antibiotics, antifungal and antiviral drugs will also be provided. The immune system begins to recover around 2 weeks after infusion of the blood stem cells, however, the immune system remains severely suppressed for several weeks and a patient is likely to remain in hospital for around 4 weeks for close medical monitoring and continuation of supportive treatment such as antibiotics. In some cases, such as in the event of severe infections, treatment in an intensive care unit may be required.

Is the treatment effective?

Although several hundred people with MS have been treated with AHSCT world-wide over the last decade, there is not yet a sufficient body of evidence for AHSCT to be recommended as routine therapy for MS. This is mainly due to a lack of gold-standard, randomised controlled clinical trials, however, data has been gathered in ongoing observational studies of people with MS treated with AHSCT. While some clinical trials are currently ongoing, the observational studies so far suggest that it may be an effective treatment for some people with MS, but it does not appear to work for everybody. The most encouraging results have been seen in people with highly active forms of relapsing MS, where it can prevent further relapses and lesions on MRI scans. People with more longstanding disease and those with progressive MS do not seem to respond to the therapy, in particular because the treatment can’t repair permanent damage already done to nerves. More research in the form of randomised controlled clinical trials is needed to provide more certainty about the safety and long-term effectiveness of the treatment and who could benefit from it.

Is it safe?

AHSCT carries a higher risk than most current MS therapies. We know that AHSCT can have some significant effects on the body such as a high risk of severe infections, effects on fertility and an increased risk of cancers. In some cases AHSCT can be fatal, carrying on average a 1.3% mortality rate (data from international studies). This means one to two people may die from the treatment for every 100 people who receive it. To date there has been no mortality among the approximate 50 people with MS who have received AHSCT in Australian teaching hospitals over the last eight years. However, large scale clinical trials have not yet been conducted to compare AHSCT against other approved MS medications, and most importantly its long term effects on the course of MS have not been definitively established.

What type of chemotherapy is used in AHSCT?

Two main types of chemotherapy are used at the majority of centres around the world – the first one called BEAM-ATG, also known as a myeloablative chemotherapy, which completely removes the immune system. Secondly there is cyclophosphamide-ATG, also known as non-myeloablative chemotherapy, which largely but not completely removes the immune system. For more information visit the AHSCT page.

Why is AHSCT being described as ‘experimental’ or ‘aggressive’ in MS when it has been used as a treatment for other diseases for decades?

AHSCT has been used in the treatment of blood cancers for several decades, however, only several hundred people with MS have received this form of treatment internationally and as a result there is a lack of clinical trial results therefore it is still considered experimental for the treatment of MS. The safety and efficacy has not yet been tested in sufficiently large gold-standard, randomised controlled trials specifically for MS and in comparison to currently available MS therapies.

Why use autologous (your own) stem cells, why not blood stem cells from someone who doesn’t have MS?

Autologous cells that are extracted from and re-infused into the same person are used in AHSCT to increase safety of the procedure and help prevent the cells being rejected by, or damaging, the body. Infusing someone else’s blood stem cells means that you are introducing an entirely new immune system that will recognise your own body as ‘foreign’ and has a much higher risk of complications (e.g. graft versus host disease in which the transplanted immune cells recognise the body as ‘foreign’ and attack it.).

Access

Who can have AHSCT?

Australian hospitals and doctors are likely to recommend AHSCT as a possible treatment only if the other approved MS therapies are not working for an individual with MS or cannot be used in an individual for other reasons. The international studies to date also suggest that AHSCT does not halt or reverse progressive forms of the disease, and it is therefore unlikely that AHSCT would be recommended as a treatment for patients with secondary progressive or primary progressive MS.

Each person’s situation is unique and decisions about any MS treatments, taking into consideration the potential benefits, risks and side effects for an individual’s particular circumstances, should be made in careful consultation with each individual’s neurologist.

Where can people get AHSCT?

Currently the treatment is provided in Australia through two observational clinical trials, at St Vincent’s, Sydney and Austin Health, Melbourne (visit www.mstrials.org.au for more information) and by a small number of other centres on a case by case basis. These centres have strict eligibility requirements that have been set by the hospital ethics committees and may only apply to limited numbers of patients with MS. It is for this reason patients need to be referred to these centres by a neurologist, who can provide a detailed clinical history and MRI findings.

Who can perform AHSCT?

AHSCT it is carried out within haematology departments at major hospitals. AHSCT is a complex medical treatment and requires supportive in-hospital medical care during the period of severe immune suppression. Neurologists experienced in the treatment of MS should be able to refer you to a suitable Haematology Unit that may be able to provide this treatment.

We recommend that the treatment should be delivered at a major teaching hospital in which the haematology unit has significant clinical experience in treating autoimmune disorders by AHSCT. The treatment should be ethically approved by the hospital and provided as part of a clinical trial and/or inclusion in a registry with long term follow up to maximise safety for the patient, and contribution to further understanding of AHSCT as an intervention for MS.

Lots of people are traveling overseas to undergo AHSCT. Is this safe?

There are a number of clinics overseas who have been accepting patients from Australia for AHSCT treatment. It is important to understand the nature of the treatment that these clinics are offering and the potential implications of receiving treatment overseas for you as an individual. It can often be very costly and carries additional considerations, both medical and personal. It is important that the patient discusses all treatment options with their Australian health care providers and with the overseas clinic.

As AHSCT is a complex medical procedure requiring significant follow-up care both in the immediate weeks following treatment, and longer term, it is important to ensure that the clinic is a fully accredited and experienced haematology centre, and that it can provide the necessary follow up care (including intensive care treatment should it be needed). It is also important to ensure that the patient receives close and ongoing medical follow-up in Australia.

For further information the National Health and Medical Research Council (NHMRC) has produced a fact sheet for people with advice on the type of questions and information that individuals should seek from the overseas provider. Although this fact sheet relates primarily to other types of stem cell treatments, the questions that a patient should ask are very similar.

How much does AHSCT cost?

At present, AHSCT is only available in Australia through observational clinical trials – in this setting treatment should be free. We are aware that people that are travelling overseas for AHSCT are doing so at considerable personal cost.

There have been lots of positive reports about AHSCT in the media. What is your view on this?

There are many stories in the media about this treatment. Reports often describe it as being a ‘miracle cure’ for MS and include personal stories of how it has given people ‘a new lease of life’. While the results of this treatment have been life-changing for some people, it is important to look at the results for a broader group of people across a longer period of time. The media reports rarely discuss the details of the treatment, which is very intensive, and do not provide a full picture regarding other people who may have received the treatment, but had a less positive response. International studies to date have shown that there are indeed some people who do very well in the first few years following this treatment, but it does not work in all cases. Research needs to continue to determine the safety and long-term effectiveness of AHSCT and who could benefit from it. A more detailed review of international studies on AHSCT can be found here.

Australian and International Research

What does the research tell us?

A number of international studies of patients undergoing AHSCT for MS have been published in the peer-reviewed scientific literature over the last 10 to 15 years. Generally the outcomes have shown that people who are younger and who still have active inflammatory disease (new lesions on MRI scans and/or relapses) may achieve better outcomes for reducing or halting disease activity. However, the majority of the studies suggest that the treatment does not halt secondary and primary progressive MS and that recovery from more long-standing disability is unlikely.

An international clinical trial of AHSCT, called the MIST trial, is currently ongoing. In Australia there are currently two sites conducting formal observational studies of AHSCT for MS with similar entry criteria. One at St Vincent’s Hospital Sydney (more information here) and one at the Austin Hospital in Melbourne (more information here).

Research needs to continue to understand the long term effects of AHSCT and its place within the range of treatments available for MS. A more detailed review of international studies on AHSCT can be found here.

What is MS Research Australia doing in relation to AHSCT?

  • MS Research Australia (with the support of the MS Society of Western Australia) has been funding the  Australian MS AHSCT Registry since 2012 and working with haematologists and neurologists to gather and analyse further data on Australians with MS treated with this procedure. This will contribute to the continuing international effort to better understand the role that AHSCT may play in the range of treatments available for MS.
  • MS Research Australia continues to advocate for Australian neurologists and haematologists to work together to deepen our understanding of the safety and efficacy of AHSCT for MS.
  • There may be some people with severe MS in Australia for whom AHSCT represents their best, or only, option for effective treatment. MS Research Australia works closely with MS Australia, the national advocacy body who has as one of their priorities to encourage dialogue between hospitals, state health departments, haematologists and neurologists to ensure that treatment can be provided in Australia for those who need it.
  • MS Research Australia together with MS Australia continue to advocate to the federal government for accessibility to all suitable treatment options for people with MS in Australia.
  • MS Research Australia is actively reviewing AHSCT studies as they become available and reporting on them via the MS Research Australia website and various communication channels.
  • MS Research Australia are preparing numerous documents and materials to assist with awareness of AHSCT.

Will you need to have all your childhood vaccinations again after receiving AHSCT?

Haematologists are still refining the best practice for re-administering vaccinations after a person has received AHSCT. It is likely that you would need to repeat some vaccinations and should discuss this with your doctor. At minimum, yearly flu vaccinations are recommended for those who have received AHSCT.

Where can I find more information about AHSCT?

If you want to know more about AHSCT, we would advise you to talk it through with your neurologist in the first instance. For additional information please see MS Research Australia’s website here.

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