Autologous hematopoietic stem cell transplantation, a form of multiple sclerosis treatment which resets the immune system, may halt progression of the disease in nearly half of patients.
The treatment prevented symptoms of aggressive disease from worsening for five years, in 46 per cent of patients, a new study led by Imperial College London found. The procedure involves aggressive chemotherapy, however, and the researchers stress the procedure carries significant risk.
Autologous hematopoietic stem cell transplantation (AHSCT), was administered in the study to patients with advanced forms of the disease that had failed to respond to other medications.
Multiple sclerosis (MS) affects around 100,000 people in the UK, and 2.3 million worldwide.
The condition is caused by the immune system malfunctioning and mistakenly attacking nerves in the brain and spinal cord. This leads to a range of symptoms including fatigue, problems with arm and leg movement, vision and balance. There is no cure but certain medications can help slow progression of the disease.
The study suggested some patients even saw a small improvement in their symptoms following the treatment. The one-off treatment aims to prevent the immune system from attacking the nerve cells.
All immune system cells are made from stem cells in the bone marrow. In the treatment, a patient is given a drug that encourages stem cells to move from the bone marrow into the blood stream, and these cells are then removed from the body.
The patient then receives high-dose chemotherapy that kills any remaining immune cells. The patient’s stem cells are then transfused back into their body to re-grow their immune system.
Previous studies have suggested this ‘resets’ the immune system, and stops it from attacking the nerve cells.
Autologous Hematopoietic Stem Cell Transplantation Risks
However, because the treatment involves aggressive chemotherapy that inactivates the immune system for a short period of time, some patients died from infections.
Out of the 281 patients who received the treatment in the study, eight died in the 100 days following the treatment. Older patients, and those with the most severe forms of the disease, were found to have a higher risk of death.
Dr Paolo Muraro, lead author of the study from the Department of Medicine at Imperial, stressed that the risks must be weighed-up against the benefits:
“We previously knew this treatment reboots or resets the immune system – and that it carried risks – but we didn’t know how long the benefits lasted. In this study, which is the largest long-term follow-up study of this procedure, we’ve shown we can ‘freeze’ a patient’s disease – and stop it from becoming worse, for up to five years.
However, we must take into account that the treatment carries a small risk of death, and this is a disease that is not immediately life-threatening.”
Most patients with multiple sclerosis have a type of the disease that has flare-ups, known as relapses, followed by an improvement in symptoms. This is called relapsing-remitting MS.
Dr Muraro explained the number of years autologous hematopoietic stem cell transplantation prevented symptoms from worsening is far greater than would be expected in untreated patients with severe forms of relapsing MS.
The study found that in patients with relapsing MS, nearly three in four (73 per cent) experienced no worsening of their symptoms five years after the treatment. Younger patients with less severe forms of the disease were more likely respond to the therapy.
However, the majority of the patients in the study had a progressive form of MS. This is a more severe form of the disease, and for which there are currently no treatments. Among these patients, one in three experienced no worsening of symptoms five years after treatment.
Some patients saw a small improvement in their symptoms, though this improvement was larger in patients with relapsing MS, compared to patients with the progressive form.
Disability in MS is assessed on a scale known as the Expanded Disability Status Scale (EDSS). In this scale, zero represents no disability, seven is wheelchair-bound, while ten is death from MS. At the beginning of the study, patients had an average EDSS score of 6.5.
Patients with relapsing MS had an average improvement in their EDSS score of 0.76, one year after the treatment. Patients with progressive MS had only a marginal improvement of 0.14.
Dr Muraro added the findings suggest larger trials of this procedure are needed.
“These findings are very promising – but crucially we didn’t have a placebo group in this study, of patients who didn’t receive the treatment. We urgently need more effective treatments for this devastating condition, and so a large randomised controlled trial of this treatment should be the next step.”
The research was supported by the Multiple Sclerosis Society UK, the Center for International Blood and Marrow Transplant Research, and by the European Blood and Marrow Transplant Autoimmune Disease Working Party.
Muraro PA, Pasquini M, Atkins HL, Bowen JD, Farge D, Fassas A, Freedman MS, Georges GE, Gualandi F, Hamerschlak N, Havrdova E, Kimiskidis VK, Kozak T, Mancardi GL, Massacesi L, Moraes DA, Nash RA, Pavletic S, Ouyang J, Rovira M, Saiz A, Simoes B, Trněný M, Zhu L, Badoglio M, Zhong X, Sormani MP, Saccardi R
Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis
JAMA Neurol. doi:10.1001/jamaneurol.2016.5867
Image: Annie Cavanagh, Wellcome Images. Human embryonic stem cells.