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STUDY: Long-term outcome of the Canadian MS BMT study finds "no disease activity"
Long-term outcome of the Canadian multiple sclerosis BMT study: efficacy and safety of treating aggressive multiple sclerosis with immunoablation and autologous stem cell transplantation
M. Freedman, H. Atkins, M. Bowman on behalf of the Canadian MS/BMT Study Group
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Immunoablation followed by autologous stem cell transplant(ASCT)has been studied as a potential treatment for MS. This study examined whether a long-lasting MS progression free response is induced for patients with active and progressive disease who are predicted to have a poor prognosis. The Canadian MS/BMT trial is a non-randomized phase II trial of intensive chemotherapy and CD34 selected ASCT in 24 patients considered at high risk of progression with aggressive MS who failed >=1year of standard treatment with and EDSS>=3 and <=6.
Patients underwent stem cell mobilization following high dose cyclophosphamide(CTX)and G-CSF. Immunoablation with CTX,anti-thymocyte globulin(ATG)and adjusted-dose busulphan was followed by infusion of an ASCT graft depleted of immune cells. Patients were closely followed every 3 months for 3 years and then every 6 months, for up to 10 years with regular clinical visits, MRI’s, immunological, neuropsychological and CSF assessments. None of the patients received disease modifying medication after the ASCT.
The first transplant occurred in October 2001 and the 24th in December 2009. The median follow-up of the group was 68 months. Serious toxicity developed in 2 patients receiving the highest dose of oral busulphan leading to a transient capillary leak syndrome in one and fatal liver necrosis in the other.
After 1700 patient-months of follow-up, not a single patient experienced any further signs of inflammatory disease activity. The EDSS stabilized or improved in 15 patients while 8 patients experienced sustained EDSS progression in the absence of inflammatory activity. Late ASCT complications included premature ovarian failure (n=14),varicella zoster reactivation (n=7) and hypothyroidism (n=5). An initial increase in the rate of brain volume loss related to the acute effects of chemotherapy was followed by a return of the rate of loss of brain tissue comparable to reports for unaffected controls.
These results demonstrate that rigorous treatment designed to ablate the auto-destructive immune system of patients with MS results in complete and long-term cessation of detectable CNS inflammatory activity without the need for chronic immunosuppressive therapy following the reestablishment of a protective and tolerant immune system. While some patients continued to show progression even in the absence of overt inflammatory activity, the disabilities in the majority of patients stabilized or improved. This is the first treatment ever shown to reverse brain atrophy in MS.
M. Freedman, H. Atkins, M. Bowman on behalf of the Canadian MS/BMT Study Group
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Immunoablation followed by autologous stem cell transplant(ASCT)has been studied as a potential treatment for MS. This study examined whether a long-lasting MS progression free response is induced for patients with active and progressive disease who are predicted to have a poor prognosis. The Canadian MS/BMT trial is a non-randomized phase II trial of intensive chemotherapy and CD34 selected ASCT in 24 patients considered at high risk of progression with aggressive MS who failed >=1year of standard treatment with and EDSS>=3 and <=6.
Patients underwent stem cell mobilization following high dose cyclophosphamide(CTX)and G-CSF. Immunoablation with CTX,anti-thymocyte globulin(ATG)and adjusted-dose busulphan was followed by infusion of an ASCT graft depleted of immune cells. Patients were closely followed every 3 months for 3 years and then every 6 months, for up to 10 years with regular clinical visits, MRI’s, immunological, neuropsychological and CSF assessments. None of the patients received disease modifying medication after the ASCT.
The first transplant occurred in October 2001 and the 24th in December 2009. The median follow-up of the group was 68 months. Serious toxicity developed in 2 patients receiving the highest dose of oral busulphan leading to a transient capillary leak syndrome in one and fatal liver necrosis in the other.
After 1700 patient-months of follow-up, not a single patient experienced any further signs of inflammatory disease activity. The EDSS stabilized or improved in 15 patients while 8 patients experienced sustained EDSS progression in the absence of inflammatory activity. Late ASCT complications included premature ovarian failure (n=14),varicella zoster reactivation (n=7) and hypothyroidism (n=5). An initial increase in the rate of brain volume loss related to the acute effects of chemotherapy was followed by a return of the rate of loss of brain tissue comparable to reports for unaffected controls.
These results demonstrate that rigorous treatment designed to ablate the auto-destructive immune system of patients with MS results in complete and long-term cessation of detectable CNS inflammatory activity without the need for chronic immunosuppressive therapy following the reestablishment of a protective and tolerant immune system. While some patients continued to show progression even in the absence of overt inflammatory activity, the disabilities in the majority of patients stabilized or improved. This is the first treatment ever shown to reverse brain atrophy in MS.
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