Efficacy and safety of autologous hematopoietic stem cell transplantation (AHSCT) versus alemtuzumab in multiple sclerosis: Systematic review and individual patient data meta-analysis.
TL;DR
AHSCT may be associated with improved inflammatory disease control and disability recovery compared with alemtuzumab in highly active MS, and should be interpreted as hypothesis-generating, given the very low certainty of the evidence and the reliance on observational data.
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.