Autologous Haematopoietic Stem Cell Transplantation (AHSCT) is sometimes referred to as HSCT or bone marrow transplant. 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.
This treatment is primarily an immune suppressing 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.
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.
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.
AHSCT is primarily an immune-suppressing chemotherapy treatment which aims to regenerate a new immune system that 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 National Health and Medical Research Council (NHMRC) has released a document, Stem Cell Treatments – Frequently Asked Questions, to provide consumers with information about stem cell treatments and the risks involved in undergoing unproven treatments.
Haematologists are still refining the best practice for re-administering vaccinations after a person has received AHSCT. It is likely that people undergoing AHSCT will need to repeat some vaccinations and should discuss this with transplant staff. At minimum, yearly flu vaccinations are recommended for those who have received AHSCT.
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 infusion into 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 may also be needed. 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.
While some clinical trials are currently ongoing, the observational studies so far suggest that AHSCT 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 long-standing disease and those with progressive MS do not seem to respond to AHSCT, in particular because the treatment can’t repair the permanent damage that has disrupted the nerves.
An international clinical trial, called the MIST clinical trial, compared the effect of AHSCT and standard disease modifying therapy (DMT) on MS progression in people with RRMS over a period of up to five years. This study showed that people treated with AHSCT had improvement in disability and fewer relapses compared to those on the standard DMTs.
Research published in 2021 has looked at the progress of 507 patients following AHSCT for several years after the procedure and found that AHSCT provides significant reversal of neurologic disability for greater than five years in patients with active inflammatory RRMS. Longer-term follow up studies are still ongoing to provide a clearer picture of the long-term effectiveness of AHSCT.
AHSCT carries a higher risk than most currently approved 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. The risk of death, however, has gradually decreased, with with recent research reporting a risk of less than 1%, compared to about 3% a decade ago. Most recently, a study published in 2021 which looked at over 500 patients treated between 2003 and 2019 in a single American hospital recorded a transplant-related mortality of 0.19%.
To date there has been no mortality among the approximately 100 people with MS who have received AHSCT in Australian teaching hospitals over the last eight years.
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.
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).
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.
Currently the treatment is provided in Australia through three observational clinical trials, at St Vincent’s, Sydney, Austin Health, Melbourne and The Alfred, 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.
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. As detailed above, 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.
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 on their return.
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.
At present, AHSCT is only available in Australia through observational clinical trials – in this setting treatment should be at no cost. We are aware that people that are travelling overseas for AHSCT are doing so at considerable financial cost to them personally.
A number of international studies of patients undergoing AHSCT for MS have been published in peer-reviewed scientific journals 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) achieve better outcomes for reducing or halting disease activity. However, most 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.
Results from a recent international clinical trial, called the MIST trial, showed that people with MS who had undergone AHSCT had improvement in disability and fewer relapses compared to those on standard DMTs.
A more detailed review of international studies on AHSCT can be found here.
In 2018, the results of an observational study of 35 people with MS who received AHSCT in Sydney were published, and like the international studies, showed that people with more active forms of MS benefitted most from the treatment. In Australia, there are currently three sites conducting formal observational studies of AHSCT for MS with similar entry criteria. One at St Vincent’s Hospital, Sydney (more information here) and two are in Melbourne at Austin Hospital (more information here) and The Alfred (more information here).