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Autologous haematopoietic stem cell transplantation in multiple sclerosis patients: safety and efficacy in long term follow-up
M. Radaelli, L. Moiola, V. Martinelli, F. Sangalli, L. Ferrč, V. Barcella, M. Comola, P. Vezzulli, R. Greco, J. Peccatori, F. Ciceri, G. Comi (Milan, IT)
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Objectives: High dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (HSCT) has been used as a treatment for patients affected by aggressive multiple sclerosis (MS), not responsive to conventional therapies. The aim of this study was to evaluate the safety and efficacy of HSCT, after immunosuppressive conditioning with thiotepa-cyclophosphamide (Thio-Cy).
Methods: Between 2006 and 2007, 9 pts (5 women) were treated with the following schedule: Cy 4 gr/m2 with G-CSF mobilization and collection of peripheral blood stem cells (PBSC); high dose immunosuppression with Thio 10 mg/Kg plus Cy 100 mg/Kg. Neither in vivo nor ex vivo T cell depletion of the graft was performed. The mean age at the time of transplantation was 27. Mean disease duration was 6,4 years. The ARR in the year before HSCT was 1,9 and the median increase of EDSS in the two years before the treatment was 2.5. At the time of mobilization median EDSS was 6.0 (2,5-8 range). The mean number of enhancing lesions at the basal brain MRI was 26 (1-67).
Results: Mobilization was successful in all cases with no serious adverse effects. The mean dose of PBSC infused was 5.7x106 CD34+cells/Kg. Haematopoietic recovery was documented safely in 9/9 patients. At a mean follow-up of 6 years severe non-malignant or malignant late effects were not reported. Transplant-related mortality was 0. In the year after HSCT we observed a significant reduction of the ARR from 1,9 to 0,3 ( p< 0,05). The mean number of enhancing lesions at the brain MRI performed 1 year after HSCT was 0,3. However seven patients experienced a relapse after a mean time of 18 months (range 11-67). After the clinical reactivation five patients began natalizumab, one glatiramer acetate and the last one i.v. cyclofosfamide. Another patient had a progressive increase of EDSS from 6 to 6.5 after 18 months whereas the last patient showed two new T2 lesions at brain MRI six year after HSCT.
Conclusion: The good safety profile of this procedure was confirmed even at a long follow-up since no serious and late adverse events were reported. After HSCT all patients obtained a significant effect on the clinical and neuroradiological disease activity in the short time. However this procedure was not sufficient to induce a real "reset" of the immune system. Low intensity HSCT might be considered as a valid and powerful induction therapy in selected patients with aggressive form of MS.
M. Radaelli, L. Moiola, V. Martinelli, F. Sangalli, L. Ferrč, V. Barcella, M. Comola, P. Vezzulli, R. Greco, J. Peccatori, F. Ciceri, G. Comi (Milan, IT)
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Objectives: High dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (HSCT) has been used as a treatment for patients affected by aggressive multiple sclerosis (MS), not responsive to conventional therapies. The aim of this study was to evaluate the safety and efficacy of HSCT, after immunosuppressive conditioning with thiotepa-cyclophosphamide (Thio-Cy).
Methods: Between 2006 and 2007, 9 pts (5 women) were treated with the following schedule: Cy 4 gr/m2 with G-CSF mobilization and collection of peripheral blood stem cells (PBSC); high dose immunosuppression with Thio 10 mg/Kg plus Cy 100 mg/Kg. Neither in vivo nor ex vivo T cell depletion of the graft was performed. The mean age at the time of transplantation was 27. Mean disease duration was 6,4 years. The ARR in the year before HSCT was 1,9 and the median increase of EDSS in the two years before the treatment was 2.5. At the time of mobilization median EDSS was 6.0 (2,5-8 range). The mean number of enhancing lesions at the basal brain MRI was 26 (1-67).
Results: Mobilization was successful in all cases with no serious adverse effects. The mean dose of PBSC infused was 5.7x106 CD34+cells/Kg. Haematopoietic recovery was documented safely in 9/9 patients. At a mean follow-up of 6 years severe non-malignant or malignant late effects were not reported. Transplant-related mortality was 0. In the year after HSCT we observed a significant reduction of the ARR from 1,9 to 0,3 ( p< 0,05). The mean number of enhancing lesions at the brain MRI performed 1 year after HSCT was 0,3. However seven patients experienced a relapse after a mean time of 18 months (range 11-67). After the clinical reactivation five patients began natalizumab, one glatiramer acetate and the last one i.v. cyclofosfamide. Another patient had a progressive increase of EDSS from 6 to 6.5 after 18 months whereas the last patient showed two new T2 lesions at brain MRI six year after HSCT.
Conclusion: The good safety profile of this procedure was confirmed even at a long follow-up since no serious and late adverse events were reported. After HSCT all patients obtained a significant effect on the clinical and neuroradiological disease activity in the short time. However this procedure was not sufficient to induce a real "reset" of the immune system. Low intensity HSCT might be considered as a valid and powerful induction therapy in selected patients with aggressive form of MS.