A large, international, long-term study of people with multiple sclerosis (MS) receiving autologous haematopoietic stem cell transplant (AHSCT) has shown that overall, 46% had no further progression of disability at 5 years following treatment.
AHSCT is a form of immunosuppressive chemotherapy that is followed by re-infusion of the patient’s own blood and immune stem cells to promote the recovery of the immune system. Evidence suggests that the treatment ‘re-sets’ the immune system to a less inflammatory state.
One of the main concerns with this treatment for MS has been the high risks associated with the treatment, especially in the some of the earlier studies, which was combined with a lack of knowledge of whether it would have a long term benefit for people with MS. In this study, 8 of 281 people died as a result of the treatment.
This study, published today in the Journal of the American Medical Association (JAMA) Neurology, is important because, unlike other published studies it has followed a larger number of patients for longer periods of time. This study also included a large proportion of people with progressive MS which has allowed a good comparison of the outcomes for people with relapsing and progressive MS.
How was the study conducted and what did it show?
The data analysis included 281 people with MS from 25 centres in 13 countries who were treated with AHSCT between 1995 and 2006 and who were followed for an average of 6.6 years (ranging from 0.2 to 16 years). The data shows that those who were younger when treated (37 years or less), those with relapsing forms of MS and who had received 2 or less prior MS treatments were more likely to respond well to the treatment. 73% of people with relapsing MS, and one third of people with progressive forms of MS, experienced no further disability progression at 5 years.
The individuals in the study were treated with a range of different types of immunosuppressive chemotherapy, with the majority (63.7%) receiving an intermediate intensity treatment such as BEAM and 18% receiving a higher intensity treatment such as busulphan, and 17.4% receiving a lower intensity treatment such as cyclophosphamide. The authors of the study could not detect any difference in disability outcomes between the different forms of chemotherapy.
The rate of disability progression before and after the treatment was also compared for 111 patients in the study. The rate of disease progression in the 12 months immediately prior to AHSCT with the 12 months immediately post treatment was compared. On average the rate for people with relapsing MS slowed and even slightly reversed going from an increase of 1.4 points on the EDSS in the 12 months prior, to a decrease of 0.76 points in the 12 months following treatment. For people with progressive disease the change wasn’t so marked, going from an increase of 0.73 EDSS points in the year prior, to an average decrease of 0.14 EDSS points in the 12 months after treatment.
Eight of the 281 people in the study (2.8%) died as a result of the transplant (within 100 days of the treatment) and the authors of the study note that this is a significant concern in a disease such as MS that is not usually immediately life-threatening. These patients were more likely to have either progressive forms of MS or received high intensity treatment.
A lower mortality rate of 1.3% was noted in a previously published study by the European Blood and Marrow Transplant Registry Autoimmune Disease Working Group (who were also a part of this collaborative study together with the Centre for International Blood and Marrow Transplant Research) for people treated in the later half of this study between 2001 to 2007. This has been attributed to improved selection of patients to exclude those with either higher levels of disability or progressive forms of MS that place them at higher risk of complications, and less frequent use of the high intensity chemotherapy regimens.
Analysis of the adverse events that were experienced at later time-points following AHSCT in this study showed that 1.1% of the patients had developed a type of cancer that is known to be associated with prior treatment with cytotoxic (chemotherapy) drugs. 5% had developed a new (or secondary) autoimmune disorder.
In a media release issued by Imperial College London, lead author Dr Paolo Muraro said “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 treatments for this devastating condition, and so a large randomised controlled trial of this treatment should be the next step.”
You can listen to a podcast interview with Dr Muraro on the JAMA Neurology website here
The five-year results were also recently published for the HALT-MS study of 24 people with severe relapsing MS who received AHSCT. Read more here
For background information about the AHSCT treatment, Australian centres and studies, and international publications on this treatment to date please visit our comprehensive AHSCT webpages here
Anyone with MS considering AHSCT as a treatment should discuss it with their neurologist as a referral is needed to be assessed for the treatment at the Australian centres currently providing AHSCT for autoimmune diseases.