Background
With over 2.3 million people living with the disabling effects of multiple sclerosis (MS) world-wide, it is no surprise that many research teams around the world have been working to find a cure for the disease. While disease-modifying therapies (DMTs) help in temporarily immobilizing the harmful immune system in MS, for some individuals these treatments are insufficient as attacks continue and disability worsens. One therapeutic procedure that has garnered attention in the MS world is called immunoablation and autologous hematopoietic stem cell transplantation (IAHSCT), which in the context of MS works by “resetting” the diseased immune system and replacing it with a healthy one. A number of studies show that the treatment has the potential to stop the progression of MS in its tracks, prevent the requirement of DMTs, and in some cases improve function. A landmark study funded by the MS Society of Canada and the Multiple Sclerosis Scientific Research Foundation (MSSRF), known as the Canadian Bone Marrow Transplantation (BMT) trial, was recently published in the highly renowned medical journal The Lancet. It found that rebooting the immune system with IAHSCT resulted in the absence of new relapses, reduction in disability progression, and for some individuals an unexpected recovery of function. Multiple groups around the world continue to study IAHSCT as a potential treatment for MS, and a new study recently published in JAMA Neurology by Dr. Paolo Muraro from Imperial College London and colleagues including MS Society-funded researchers Dr. Atkins and Dr. Freedman looks further into these trials and what they can tell us about the long term benefits and risks of IAHSCT.
The Study
The study involved looking at a cohort of people living with MS who received IAHSCT between 1996 and 2006. The team analyzed data from 281 participants from 25 centres across 13 countries that underwent the treatment. They examined demographic and clinical data (EDSS score, type of MS, treatment history, as well as the type of chemotherapy regimen that was administered- high, intermediate, or low intensity). The researchers looked at the proportion of people who had progression-free survival, meaning their disability level stayed the same before and after the treatment. They based this assessment on the observed changes in Expanded Disability Status Score (EDSS).
Results
MS progression was halted in 46% of all individuals at 5 years post-IAHSCT. The study also determined that the progression of MS after the IAHSCT is more likely to occur in (1) older versus younger people with MS (2) those with progressive MS versus relapsing-remitting MS and (3) individuals that previously were on more than two DMTs. For example, 73% of people with relapsing-remitting MS compared with 33% of people with secondary progressive MS experienced an absence of disease progression at the 5 year post-treatment assessment.
In a subgroup of 111 people that were further analyzed, those individuals with relapsing-remitting MS showed an improvement in disability following IAHSCT (EDSS change of -0.76), and for people with progressive MS improvement was also observed but to a lesser degree (EDSS change of -0.14).
There were 8 deaths reported within the first 100 days after transplant, which were related to the treatment.
Comment
Many of the studies previously published on IAHSCT have been limited by smaller numbers of people with MS, whereas the strength of the findings from Dr. Muraro and his team arises from the assessment of a larger cohort of individuals with MS from around the world who underwent treatment, and provides insight into the long-term effectiveness and safety of the procedure. Furthermore, the study will help the clinical and research communities better understand the role of IAHSCT in progressive MS and whether a prominent inflammatory presence must first be identified to ensure that the treatment will provide benefit. This study further shows that the use of IAHSCT for MS must be approached with caution as the use of aggressive chemotherapy carries significant risks. In Canada, IAHSCT has been studied as a treatment for people with highly inflammatory, rapidly advancing relapsing-remitting MS that does not respond to available therapies.
Overall, the findings from this study provide insight into the long-term impact of IAHSCT treatment in people living with all forms of MS, and serves as a driving force for larger, well-designed trials that could compare IAHSCT with other available DMTs or against a placebo treatment. It provides information that will help guide decisions of people with MS and health care professionals who are considering IAHSCT, and paves the way for ongoing research in the application of stem cells for MS. Visit the MS Society’s website to view a list of clinical trials that look at IAHSCT for MS.
Source:
Muraro PA et al. (2017) Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. JAMA Neurology. [Epub ahead of print]