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.
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.
Authors: T Koudriavtseva; A J Thompson; M Fiorelli; C Gasperini; S Bastianello; A Bozzao; A Paolillo; A Pisani; S Galgani; C Pozzilli Journal: J Neurol Neurosurg Psychiatry Date: 1997-03 Impact factor: 10.154
Authors: A Fassas; A Anagnostopoulos; A Kazis; K Kapinas; I Sakellari; V Kimiskidis; A Tsompanakou Journal: Bone Marrow Transplant Date: 1997-10 Impact factor: 5.483
Authors: D M Karussis; U Vourka-Karussis; D Lehmann; H Ovadia; R Mizrachi-Koll; A Ben-Nun; O Abramsky; S Slavin Journal: J Clin Invest Date: 1993-08 Impact factor: 14.808
Authors: Richard K Burt; Paolo A Muraro; Dominique Farge; Maria Carolina Oliveira; John A Snowden; Riccardo Saccardi; Xiaoqiang Han; Kathleen Quigley; Valquiria Bueno; Daniela Frasca; Denis Fedorenko; Joachim Burman Journal: Bone Marrow Transplant Date: 2021-04-28 Impact factor: 5.483
Authors: M A Rocca; T Mondria; P Valsasina; M P Sormani; Z H Flach; P A Te Boekhorst; G Comi; R Q Hintzen; M Filippi Journal: AJNR Am J Neuroradiol Date: 2007-09-20 Impact factor: 3.825
Authors: D M C Brinkman; C M Jol-van der Zijde; M M ten Dam; P A W te Boekhorst; R ten Cate; N M Wulffraat; R Q Hintzen; J M Vossen; M J D van Tol Journal: J Clin Immunol Date: 2007-08-10 Impact factor: 8.317