Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis
- J P A Samijn1,
- P A W te Boekhorst2,
- T Mondria1,
- P A van Doorn1,
- H Z Flach3,
- F G A van der Meché1,
- J Cornelissen2,
- W C Hop4,
- B Löwenberg2,
- R Q Hintzen1
- 1Department of Neurology, Erasmus Medical Centre Rotterdam, Postbox 2040, 3000 CA Rotterdam, The Netherlands
- 2Department of Haematology, Erasmus Medical Centre Rotterdam
- 3Department of Radiology, Erasmus Medical Centre Rotterdam
- 4Department of Biostatistics, Erasmus Medical Centre Rotterdam
- Correspondence to: Dr R Q Hintzen Department of Neurology, MS Centre ErasMS, Erasmus MC, Postbox 2040, 3000 CA Rotterdam, The Netherlands;
- Received 20 January 2005
- Accepted 29 April 2005
- Revised 12 April 2005
Background: Certain stem cell transplantation procedures might slow down inflammatory pathology in multiple sclerosis (MS).
Aims: To halt disease progression in aggressive MS by a bone marrow transplantation (BMT) protocol aimed at maximum T cell suppression.
Methods: Autologous BMT was performed in 14 patients with rapid secondary progressive MS (median EDSS score at baseline, 6; median disease duration, five years). To accomplish rigorous T cell ablation, a strong conditioning protocol was chosen—cyclophosphamide, total body irradiation, and antithymocyte globulin. To minimise the possibility of reinfusing mature T cells in the graft, bone marrow, not peripheral blood, was used as the CD34+ stem cell source.
Results: Median follow up was 36 months (range, 7–36). Post-transplant haemopoietic recovery was successful in all patients. Early toxicity included Epstein-Barr virus related post-transplantation lymphoproliferative disorder. Longterm effects were development of antithyroid antibodies (three) and myelodysplastic syndrome (one). One patient died of progressive disease five years after transplantation. Treatment failure, defined by EDSS increase sustained for six months or more, was seen in nine patients and stabilisation or improvement in five. Other clinical parameters generally showed the same outcome. No gadolinium enhanced lesions were seen on post-treatment magnetic resonance imaging, in either cerebral or spinal cord scans. However, cerebrospinal fluid oligoclonal bands remained positive in most cases.
Conclusions: This strong immunosuppressive regimen did not prevent clinical progression in patients with aggressive secondary MS. The lack of efficacy, together with some serious side effects, does not favour the use of similar rigorous T cell depleting protocols in the future.
- ATG, antithymocyte globulin
- BMT, bone marrow transplantation
- CSF, cerebrospinal fluid
- MRI, magnetic resonance imaging
- MS, multiple sclerosis
Competing interests: none declared