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. 2012 Jun;18(6):825-34.
doi: 10.1177/1352458512438454. Epub 2012 Mar 1.

A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper

R Saccardi  1 , M S Freedman, M P Sormani, H Atkins, D Farge, L M Griffith, G Kraft, G L Mancardi, R Nash, M Pasquini, R Martin, P A Muraro; European Blood and Marrow Transplantation Group; Center for International Blood and Marrow Research; HSCT in MS International Study Group
Collaborators, Affiliations
Free PMC article

A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper

R Saccardi et al. Mult Scler. 2012 Jun.
Free PMC article

Abstract

Background: Haematopoietic stem cell transplantation (HSCT) has been tried in the last 15 years as a therapeutic option in patients with poor-prognosis autoimmune disease who do not respond to conventional treatments. Worldwide, more than 600 patients with multiple sclerosis (MS) have been treated with HSCT, most of them having been recruited in small, single-centre, phase 1-2 uncontrolled trials. Clinical and magnetic resonance imaging outcomes from case series reports or Registry-based analyses suggest that a major response is achieved in most patients; quality and duration of response are better in patients transplanted during the relapsing-remitting phase than in those in the secondary progressive stage.

Objectives: An interdisciplinary group of neurologists and haematologists has been formed, following two international meetings supported by the European and American Blood and Marrow Transplantation Societies, for the purpose of discussing a controlled clinical trial, to be designed within the new scenarios of evolving MS treatments.

Conclusions: Objectives of the trial, patient selection, transplant technology and outcome assessment were extensively discussed. The outcome of this process is summarized in the present paper, with the goal of establishing the background and advancing the development of a prospective, randomized, controlled multicentre trial to assess the clinical efficacy of HSCT for the treatment of highly active MS.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1.
Figure 1.
Estimated efficacy versus risks of approved and experimental therapies for MS. The plot indicates estimated, approximate risks vs. efficacy measures for some approved and experimental MS treatments. Estimated risks of life threatening unwanted effects are obtained from data available in the current literature.39–50 The percent relapse suppression observed in treated patients is presented as a surrogate of efficacy. The list of treatments is not meant to be exhaustive but to only include the agents that have immediate relevance for the HSCT trial design. Abbreviations: GA, glatiramer acetate; IFN-β, interferon beta; FTY, fingolimod; Mitox., mitoxantrone; CY, cyclophosphamide, Nataliz., natalizumab; Alemt., alemtuzumab, Hi-CY, high-dose cyclophosphamide, HSCT, autologous hematopoietic stem cell transplantation.
Figure 2.
Figure 2.
Prospective clinical trials for HSCT in MS. Choice of trial design. BAAT, best available and approved treatment; DMA, disease-modifying agent; HSCT, haematopoietic stem cell transplantation.
Figure 3.
Figure 3.
Prospective, controlled trial for HSCT in a multiple sclerosis. Trial design.
Figure 4.
Figure 4.
Transplant methodology. The boxes represent variables related to the intensity of the treatment. (from Saccardi R and Gualandi F. Autoimmunity, 2008; 41(8): 570-576.)
Figure 5.
Figure 5.
Proportion of multiple sclerosis forms at transplant baseline across the years. EBMT Registry data.
See this image and copyright information in PMC

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References

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