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.
ReviewAutologous haematopoietic-stem-cell transplantation for multiple sclerosis
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
References (69)
- et al.
Multiple sclerosis
Lancet
(2002) - et al.
Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial
Lancet
(2002) - et al.
High-dose immunosuppression and hematopoietic stem cell transplantation in autoimmune disease: clinical review
Biol Blood Marrow Transplant
(2002) - et al.
Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation
Blood
(1996) - et al.
Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors
Blood
(1998) - et al.
Immune reconstitution following allogeneic peripheral blood progenitor cell transplantation: comparison of recipients of positive CD34+ selected grafts with recipients of unmanipulated grafts
Exp Hematol
(1999) - et al.
Increased incidence of cytomegalovirus disease after autologous CD34-selected peripheral blood stem cell transplantation
Blood
(1999) - et al.
Stem cell transplantation for multiple sclerosis: what is the evidence
Blood Rev
(2003) - et al.
Immunoablative therapy with autologous stem cell transplantation in the treatment of poor risk multiple sclerosis
Transplant Proc
(2001) - et al.
High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis
Blood
(2003)
Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores
Blood
Peripheral blood stem cell transplantation in multiple sclerosis with busulfan and cyclophosphamide conditioning: report of toxicity and immunological monitoring
Biol Blood Marrow Transplant
Monoclonal and oligoclonal gammopathy after bone marrow transplantation
Blood
Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation
Blood
Immune reconstitution after autologous hematopoietic stem cell transplantation
Mayo Clin Proc
Multiple sclerosis
N Engl J Med
Key issues in the diagnosis and treatment of multiple sclerosis: an overview
Neurology
Bone marrow transplantation
N Engl J Med
Transplantation of autoimmune potential, I: development of antinuclear antibodies in H−2 histocompatible recipients of bone marrow from New Zealand Black mice
Proc Natl Acad Sci USA
Experimental basis of hematopoietic stem cell transplantation for treatment of autoimmune diseases
J Leukoc Biol
Immune ablation followed by allogeneic or autologous bone marrow transplantation: a new treatment for severe autoimmune diseases
Stem Cells
Bone marrow transplantation for autoimmune diseases
Acta Haematol
Pre-existing autoimmune disease in patients with long-term survival after allogeneic bone marrow transplantation
J Rheumatol Suppl
Bone marrow transplantation in multiple sclerosis
J Neurol
Changes in autoimmune thyroid disease following allogeneic bone marrow transplantation
Bone Marrow Transplant
Treatment of relapsing experimental autoimmune encephalomyelitis in rats with allogeneic bone marrow transplantation from a resistant strain
Bone Marrow Transplant
Treatment of relapsing experimental autoimmune encephalomyelitis with largely MHC-matched allogeneic bone marrow transplantation
Transplantation
Effective treatment of relapsing experimental autoimmune encephalomyelitis with pseudoautologous bone marrow transplantation
Bone Marrow Transplant
Blood and marrow stem cell transplants in auto-immune disease: a consensus report written on behalf of the European League against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT)
Bone Marrow Transplant
Hematopoietic stem cell transplantation for multiple sclerosis: a retrospective multicenter study
J Neurol
Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation
J Neurol
Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers
N Engl J Med
Multiple sclerosis flares associated with recombinant granulocyte colony-stimulating factor
Neurology
A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis
Bone Marrow Transplant
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Autologous stem cell transplantation in neurological inflammatory diseases
2023, Pratique Neurologique - FMCStem cell therapies in age-related neurodegenerative diseases and stroke
2017, Ageing Research ReviewsThe hematopoietic system in the context of regenerative medicine
2016, MethodsCitation Excerpt :It has also successfully reversed autoimmune disorders including SLE [226,230,235,236,251,259,260,275], Type I diabetes [238,240,243,248,249,261], pemphigus vulgaris [275,276], and experimental allergic encephalomyelitis (a preclinical model for multiple sclerosis) [234,237,246,247,259,277]. However, results of clinical trials using HSC transplantation to treat “true” multiple sclerosis have been more mixed; some trials have reported very positive impact on clinical scores and disease progression [277–280], while others have found either no improvement at all, or perhaps even a worsening of neuroinflammation and demyelination following HSC transplant [281,282]. While only some autoimmune diseases can be treated by autologous HSC transplantation, allogeneic HSC transplantation has no such limitations.
Myeloid cell-based therapies in neurological disorders: How far have we come?
2016, Biochimica et Biophysica Acta - Molecular Basis of DiseaseCitation Excerpt :The capacity of BMDCs to engraft in the adult CNS makes them attractive vehicles for the delivery of therapeutic genes to sites of brain damage. However, clinical trials with BMDCs in patients with neurological disorders have so far failed to demonstrate robust protective effects [23–25]. The difficulties in translating the preclinical findings to the bedside may result from the incomplete characterization of the bone marrow (BM)-derived cell population that targets the CNS and provides therapeutic effects in neurological disorders.