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Another brick in the wall: further evidence supporting the role of haematopoietic stem cell transplantation in treating multiple sclerosis
  1. Harold L Atkins
  1. The Ottawa Hospital Blood and Marrow Transplant Program, Ottawa, ON K1H 8L6, Canada
  1. Correspondence to Dr Harold L Atkins, The Ottawa Hospital Blood and Marrow Transplant Program, Ottawa, ON K1H 8L6, Canada; hatkins{at}

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Haematopoietic stem cell transplantation is able to control multiple sclerosis in patients who have failed modern disease modifying drugs

Over the last 30 years, disease-modifying drugs (DMDs) that target the immune system either by lymphocytoreduction or by modulating lymphocyte function have become available to treat multiple sclerosis. While all control the episodic acute inflammation of the central nervous system, disease activity ultimately breaks through inevitably resulting in progressive disabilities. It is against this background that the role of autologous haematopoietic stem cell transplantation (aHSCT) has been examined. A combination of antibody and chemotherapeutic agents destroys the autoreactive disease-mediating immune system while an infusion of an autologous haematopoietic stem cell graft accelerates haematopoietic reconstitution and provides the seeds for a naïve replacement immune system. Evidence supporting a role for aHSCT continues to accumulate through prospective phase II cohort studies, registry-based long-term follow-up observations and randomised trials.1

The JNNP study by Moore et al 2 is important, demonstrating that transplantation of an unmanipulated hematopoietic stem cell graft following BEAM (BEAM: carmustine, etoposide, cytarabine, melphalan chemotherapy) chemotherapy and equine antithymocyte globulin is beneficial even for patients who have ongoing disease activity despite failing at least two DMDs, including a high proportion that failed newer more effective DMDs. This single-centre study of 35 patients showed a relapse-free survival of 90%, a progression-free survival of 73% and an event-free survival of 60%, 3 years after aHSCT. To put this in context, and similar to the results of other prospective trials of aHSCT, multiple sclerosis is controlled in a larger per cent of the treated population then even the most effective DMDs.3

The absence of a direct randomised comparator group might leave interpretation of the study open to bias; however, this does not minimise the value of this data. A treatment that controls both the acute inflammatory events while preventing the accumulation of disability over a long follow-up period would herald a change in the natural history of MS. While the outcomes of this study at a median follow-up of 3 years are promising, monitoring outcomes of the cohort over another 5–10 years will strengthen any conclusion about the benefit of the treatment.

Admirably, reflecting the skill of the treating team, there were no deaths related to aHSCT in the cohort. However, the 95% CI of this mortality rate would extend from 0 up to a potential 10%. This procedure requires the expertise of healthcare teams proficient in the care of patients undergoing aHSCT and the results of aHSCT improve with the team’s increasing familiarity in performing aHSCT for MS.4

Caution should be used in likening heavily pretreated MS with patients with advanced cancer. While cancers generally become more resistant with each treatment, with lower response rates and shorter remissions, this may not be the case in MS. It is possible that patients failing more agents have just cycled through DMDs more quickly and may have comparable disease activity as measured by total number of relapses or EDSS to a group whose treatment was not altered with every new solitary lesion or clinical relapse. Rather than ‘becoming more resistant’, the need for more potent immunosuppressive agents may reflect a ‘stronger’ initial immune response driving MS. If so, a treatment such as aHSCT that controls MS activity in these patients is likely to be a more potent therapy. Thus, the results of the trial by Moore et al are another important element in the foundation supporting the role of aHSCT in the treatment of patients with MS.



  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

  • Data sharing statement No additional unpublished information available.

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