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Post by NHE »

Hematopoietic Stem Cell Transplantation in People With Active Secondary Progressive Multiple Sclerosis
Neurology. 2022 Dec 21;10.1212

Background and objectives: Uncontrolled evidence suggests that autologous hematopoietic stem cell transplantation (AHSCT) can be effective in people with active secondary progressive multiple sclerosis (SPMS). In this study we compared the effect of AHSCT with that of other anti-inflammatory disease modifying therapies (DMT) on long-term disability worsening in active SPMS.

Methods: We collected data from the Italian-Bone-Marrow-Transplantation-Study-Group and the Italian-Multiple-Sclerosis-Register. Patients were considered eligible if treatment had been started after the diagnosis of SPMS. Disability worsening was assessed by the cumulative proportion of patients with a 6-months confirmed-disability-progression (CDP) according to the Expanded-Disability-Status-Scale (EDSS) score. Key secondary endpoints were the EDSS time-trend after treatment start and the prevalence of disability improvement over time. Time to CDP was assessed by means of proportional hazard Cox regression models. A linear mixed model with a time*treatment group interaction was used to assess the longitudinal EDSS time-trends. Prevalence of improvement was estimated using a modified Kaplan-Meier estimator and compared between groups by bootstrapping the area under the curve.

Results: 79 AHSCT-treated patients and 1975 patients treated with other DMT (beta-interferons, azathioprine, glatiramer-acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate, alemtuzumab) were matched to reduce treatment selection bias using propensity-score and overlap weighting approaches. Time to first CDP was significantly longer in transplanted patients (HR=0.50; 95%CI= 0.31-0.81; p=0.005), with 61.7% of transplanted patients free from CPD at 5 years. Accordingly, EDSS time-trend over 10 years was higher in patients treated with other DMT than in AHSCT-treated patients (+0.157 EDSS points per year compared to -0.013 EDSS points per year; interaction-p<0.001). Patients who underwent AHSCT were more likely to experience a sustained disability improvement: 34.7% of patients maintained an improvement (a lower EDSS than baseline) 3 years after transplant versus 4.6% of patients treated by other DMT (p<0.001).

Discussion: The use of AHSCT in people with active SPMS is associated with a slowing of disability progression and a higher likelihood of disability improvement compared to standard immunotherapy.
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