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From ECTRIMS 2011: Neurological recovery following treatment of aggressive multiple sclerosis with immunoablation and autologous stem cell transplantation
M.S. Freedman, H.L. Atkins, M.J. Bowman on behalf of the Canadian MS/BMT Study Group
Background & Objectives: Immunoablation followed by autologous stem cell transplant (ASCT) is being studied as a potential treatment for MS to establish if a long-lasting MS progression free response can be induced for patients with active and progressive disease who are predicted to have a poor prognosis.
Methods: 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 >=1 year of standard treatment 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.
Results: The first transplant occurred in October 2001 and the 24th transplant was completed in December 2009 with a median follow-up of 62 months. Most patients developed expected organ toxicities and febrile neutropenia but these were generally mild and transient. Serious toxicity developed in 2 patients receiving the highest dose of busulphan leading to fatal liver necrosis in one. After 1,571 patient-months of follow-up, not a single patient has experienced any further signs of inflammatory disease manifesting as relapses or new MRI lesions. 16/24 patients have stabilized or improved in their level of disability as measured by their EDSS, while 7 patients have experienced ongoing progression of disabilities. Overall survival reaches a plateau of 95%. The long term event – free (relapse, progression, death) survival reached a plateau of ~70%.
Conclusions: The results to date demonstrate that high intensity immunosuppression with ASCT is a viable treatment option for patients with very poor prognosis and can change the natural history of aggressive MS.
M.S. Freedman, H.L. Atkins, M.J. Bowman on behalf of the Canadian MS/BMT Study Group
Background & Objectives: Immunoablation followed by autologous stem cell transplant (ASCT) is being studied as a potential treatment for MS to establish if a long-lasting MS progression free response can be induced for patients with active and progressive disease who are predicted to have a poor prognosis.
Methods: 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 >=1 year of standard treatment 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.
Results: The first transplant occurred in October 2001 and the 24th transplant was completed in December 2009 with a median follow-up of 62 months. Most patients developed expected organ toxicities and febrile neutropenia but these were generally mild and transient. Serious toxicity developed in 2 patients receiving the highest dose of busulphan leading to fatal liver necrosis in one. After 1,571 patient-months of follow-up, not a single patient has experienced any further signs of inflammatory disease manifesting as relapses or new MRI lesions. 16/24 patients have stabilized or improved in their level of disability as measured by their EDSS, while 7 patients have experienced ongoing progression of disabilities. Overall survival reaches a plateau of 95%. The long term event – free (relapse, progression, death) survival reached a plateau of ~70%.
Conclusions: The results to date demonstrate that high intensity immunosuppression with ASCT is a viable treatment option for patients with very poor prognosis and can change the natural history of aggressive MS.
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