Professor Richard Burt and his colleagues at the Northwestern University in Chicago have published preliminary results for a case series of 151 people with MS treated by autologous haematopoietic stem cell transplant (AHSCT).
The patients were treated at a single centre between 2003 and 2014, and have been followed up for between 6 months and 4 years.
Overall, the disability level for a proportion of the participants improved by at least 0.5 points on the EDSS scale at 3 years, and measures of cognition and quality of life also showed some improvements.
The paper was published in the journal JAMA and describes the results for people with MS treated either as part of a registered observational study (55 patients) or who were treated off the study protocol (96 patients). Six of the participants were not included in the final analysis due to problems with follow-up.
123 people in the study had the relapsing form of MS, and 28 had secondary progressive MS. The average age of participants was 36 years, although disease duration varied widely between 9 months and 22 years (average 6.6 years). All had failed at least one disease modifying therapy.
As for the HALT-MS study reported earlier this month, the results for this group of patients are consistent with other international studies suggesting that people with active relapsing MS with less than 10 years disease duration, were more likely to respond to this form of treatment. People with secondary progressive MS were unlikely to respond. However, in this study, age was not associated with response to treatment. (For a full review of published international literature on AHSCT for MS, prepared by MS Research Australia, please click here.)
Disease activity-free survival (as defined by the absence of any relapses or new MRI lesion activity, and no worsening of disability score) was 80% of participants at 2 years following treatment and 68% of the participants at 4 years. For relapse prevention, 89% of patients were relapse free at 2 years and 80% at 4 years. Some participants showed improvements in their disability scores, with 50% of participants (41 out of 82 people followed beyond two years) showing an improvement of 1 point on the EDSS score at two years, and 64% (23 out of 36 people) at 4 years.
These are encouraging results, however, the authors acknowledge that the study is limited by being conducted at a single study centre with no blinding (participants and assessing doctors were aware of the treatment the patient had received) and no comparison treatment was included in the study. A comparison group allows participants to be randomly allocated into one of two or more treatment groups (‘randomisation’), and also allows comparison between the groups over time. Approaches such as blinding and randomisation are frequently used to improve the reliability of clinical trial results and to help avoid potential biases.
The treatment protocol used in this study was a non-myeloablative treatment, meaning that the immune system is not completely destroyed, and so the stem cell transplantation is able to assist in reconstituting the immune system more quickly following the treatment.
In this study, there were no deaths in the immediate period following chemotherapy and transplantation. Side effects were consistent with the nature of the treatment and other studies of both myeloablative and non-myeloablative AHSCT, and included minor post-transplant infections and bleeding problems.
In an accompanying editorial in the same issue of the journal, Professor Hauser from the University of California San Francisco, agrees that the results of the study are encouraging, but also stresses the limitations of the study including lack of blinding and randomisation. He also notes that it may not be possible in this study to distinguish between improvements in EDSS due to recovery from relapses experienced just prior to transplantation, and EDSS recovery due the treatment itself. He calls for longer term follow-up and further controlled clinical research to increase confidence in the long term benefits and understanding of any long-term adverse effects of this form of treatment.
Dr Burt and the team at Chicago, together with a number of other sites in the US, UK and Sweden are currently conducting a randomised controlled trial of AHSCT in comparison to other approved MS medications.
For further information on AHSCT for MS and for the MS Research Australia position statement please click here.