Efficacy and safety of autologous hematopoietic stem cell transplantation (AHSCT) versus alemtuzumab in multiple sclerosis: Systematic review and individual patient data meta-analysis

Why clinicians should know about it

• Picked for Transplantation (top studies of the week, 20 September 2026): Multiple sclerosis therapy comparison, unrelated to transplantation
• Picked for Neurology (clinical) (top studies of the week, 20 September 2026): AHSCT vs alemtuzumab comparative effectiveness meta-analysis
• Picked for Radiology, Radiation Oncology, Nuclear Medicine, Medical Physics and Imaging (top studies of the week, 20 September 2026): AHSCT vs alemtuzumab MS review, no imaging focus

Abstract

BACKGROUND: Autologous hematopoietic stem cell transplantation (AHSCT) and alemtuzumab are high-efficacy immune reconstitution therapies for highly active multiple sclerosis (MS), but direct comparative evidence remains limited. OBJECTIVE: To compare the efficacy and safety of AHSCT versus alemtuzumab in patients with highly active MS. METHODS: The literature search involved PubMed, Scopus, Web of Science, and Embase up to November 2025. Observational studies comparing AHSCT and alemtuzumab were included. Time-to-event outcomes were reconstructed from Kaplan-Meier curves using IPD methods. We pooled hazard ratios (HRs) and risk ratios (RRs) using random-effects models with Hartung-Knapp adjustment. Risk of bias was assessed using ROBINS-I, and certainty of evidence was evaluated using GRADE. RESULTS: Ten studies (n = 1887 patients) were included. AHSCT was associated with a higher probability of EDSS improvement (HR 2.12, 95% CI 1.38-3.27) and improved relapse-free survival (HR 0.33, 95% CI 0.19-0.58), with low heterogeneity. A higher likelihood of achieving NEDA was also observed (HR 0.39, 95% CI 0.22-0.67). No significant difference was found in disability progression or MRI activity. Safety analyses showed no statistically significant differences in overall adverse events or mortality, although autoimmune thyroid disease was significantly more frequent with alemtuzumab (RR 0.39, 95% CI 0.30-0.49). Estimates for infection-related outcomes were highly imprecise. CONCLUSIONS: AHSCT may be associated with improved inflammatory disease control and disability recovery compared with alemtuzumab in highly active MS. However, given the very low certainty of the evidence and the reliance on observational data, these findings should be interpreted as hypothesis-generating. Well-designed randomized controlled trials are required to establish comparative effectiveness and safety.

Abstract as published, via PubMed.