Abstract
The purpose of the study was to determine the long-term safety and effectiveness of high-dose immunosuppressive therapy (HDIT) followed by autologous hematopoietic cell transplantation (AHCT) in advanced multiple sclerosis (MS). TBI, CY and antithymocyte globulin were followed by transplantation of autologous, CD34-selected PBSCs. Neurological examinations, brain magnetic resonance imaging and cerebrospinal fluid (CSF) for oligoclonal bands (OCB) were serially evaluated. Patients (n=26, mean Expanded Disability Status Scale (EDSS)=7.0, 17 secondary progressive, 8 primary progressive, 1 relapsing/remitting) were followed for a median of 48 months after HDIT followed by AHCT. The 72-month probability of worsening ⩾1.0 EDSS point was 0.52 (95% confidence interval, 0.30–0.75). Five patients had an EDSS at baseline of ⩽6.0; four of them had not failed treatment at last study visit. OCB in CSF persisted with minor changes in the banding pattern. Four new or enhancing lesions were seen on MRI, all within 13 months of treatment. In this population with high baseline EDSS, a significant proportion of patients with advanced MS remained stable for as long as 7 years after transplant. Non-inflammatory events may have contributed to neurological worsening after treatment. HDIT/AHCT may be more effective in patients with less advanced relapsing/remitting MS.
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Acknowledgements
We acknowledge the study coordinators and data technicians who contributed to this study. We thank Helen Crawford, Bonnie Larson and Sue Carbonneau for their excellent support in preparing this manuscript. This work was supported by contract awards N01AI05419-16-0-1 (PI Keith Sullivan) and N01-AI-05408 (PI Chris Bredeson) from the National Institute of Allergy and Infectious Diseases, and grants numbered P01HL036444 from the National Heart, Lung and Blood Institute, P30CA015704 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services; and H133B980017 from the US Department of Education's National Institute on Disability and Rehabilitation Research. We also thank Amgen for their generous gift of filgrastim (G-CSF).
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This work was presented in abstract form in part at the American Academy of Neurology, 2008.
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Bowen, J., Kraft, G., Wundes, A. et al. Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results. Bone Marrow Transplant 47, 946–951 (2012). https://doi.org/10.1038/bmt.2011.208
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DOI: https://doi.org/10.1038/bmt.2011.208
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