Elsevier

The Lancet Neurology

Volume 4, Issue 1, January 2005, Pages 54-63
The Lancet Neurology

Review
Autologous haematopoietic-stem-cell transplantation for multiple sclerosis

https://doi.org/10.1016/S1474-4422(04)00966-4Get rights and content

Summary

Intense immunosupression followed by autologous haematopoietic-stem-cell transplantation (HSCT) is being assessed as a potential treatment for patients with severe multiple sclerosis (MS). The treatment was developed from research that showed autologous HSCT was as effective as allogeneic HSCT in the treatment of experimental autoimmune encephalomyelitis. The treatment is thought to eradicate the defective immune system, and the infused haematopoietic stem cells reconstitute an immune system that is more tolerant to the nervous system. About 250 patients with MS have been treated with autologous HSCT as part of phase I and phase II open trials. Autologous HSCT seems feasible in MS and assessment with clinical and MRI measures suggests it induces a profound and long-lasting suppression of inflammation. The course of MS seems to be stabilised after autologous HSCT, especially in ambulatory patients with evidence of active disease. Autologous HSCT deserves further study in randomised controlled trials.

Section snippets

Rationale and experimental models

The hypothetical basis for the use of allogeneic HSCT to treat MS is that the procedure will eradicate the abnormal immune system and establish a new one that is more tolerant to the nervous system. Since Morton and Siegel described the development of antinuclear antibodies in normal mice after allogeneic HSCT from NZB mice—a strain of mice that spontaneously develop a systemic-lupus-erythematosus-like disease6—experimental and clinical reports have confirmed the possibility of patients

Practical issues in autologous HSCT

As in other medical procedures, the immediate toxicity of the autologous HSCT depends on the expertise of the transplant team and the measures taken to prevent infectious complications. To guarantee the lowest rate of complications in patients with MS who have autologous HSCT, they must be treated by transplant teams with approved protocols for allogeneic HSCT and in isolated rooms with laminar airflow.16

Autologous HSCT is a complicated procedure with several steps that have not been done

Clinical studies

Worldwide about 250 patients with MS have been treated with autologous HSCT. The Autoimmune Disease Working Party registry of the European Group for Blood and Marrow Transplantation53 collected 168 cases up to June 23, 2004 (Dr A Tyndall for the European Group for Blood and Marrow Transplantation, personal communication). Data on toxicity and clinical outcome for the first 85 patients are available as result of a multicentre retrospective observational analysis.17 In addition, several

Conclusion

Phase I and phase II clinical trials on autologous HSCT for MS have provided important insights on the morbidity and the outcome of MRI and CSF variables. The findings suggest that the treatment is feasible in severe forms of MS provided that strict eligibility criteria are applied to patients and centres. Although the treatment induces a profound and long-lasting suppression of MRI activity associated with inflammation, whether the procedure is really effective in modifying the progressive

Search strategy and selection criteria

Studies were identified by searches of PubMed from 1996 to June 2004 with the terms “multiple sclerosis”, “magnetic resonance imaging”, and “oligoclonal bands” and combining these terms with “haematopoietic-stem-cell transplantation” or “bone-marrow transplantation”. Studies were also identified from the personal files of the authors. Abstracts and reports from meetings were not included.

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