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Efficacy and safety of autologous hematopoietic stem-cell transplantation in multiple sclerosis: a systematic review and meta-analysis

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Abstract

Background

Autologous hematopoietic stem-cell transplantation (AHSCT) has been utilized as a treatment option for multiple sclerosis (MS) since 1995. However, this procedure has not been widely implemented in clinical practice owing to its mortality risk. Here, we conduct a meta-analysis to evaluate the long-term efficacy and safety of AHSCT in MS treatment, aiming to optimize the benefit/risk ratio of this therapeutic strategy.

Methods

We searched the PubMed Web site and clinicaltrials.gov databases. The efficacy endpoints were progression-free survival (PFS) and disease activity-free survival. The safety outcomes were transplant-related mortality (TRM) and overall deaths.

Results

Eighteen eligible studies with a total of 732 participants were enrolled. The PFS was 75% (95% CI, 0.69–0.81), and the estimate of disease activity-free survival was 61% with 48-month follow-up. Subgroups analysis showed that low- and intermediate-intensity regimens were associated with higher PFS 80%. Relapsing remitting MS (RRMS) benefited more from AHSCT than other MS subtypes with PFS 85%. Patients with Gd+ lesions at baseline MRI responded better to AHSCT with PFS 77%. The estimate of TRM was 1.34% (95% CI, 0.39–2.30), and the overall mortality was 3.58%. TRM was significantly higher in high-intensity regimen studies (3.13%) and in older studies (1.93%) performed before 2006.

Conclusions

This meta-analysis provides evidences that AHSCT can induce long-term remissions for MS patients with a high degree of safety. We indicate low- and intermediate-intensity regimens and RRMS patients with the presence of Gd+ lesions at baseline MRI can obtain the optimal benefit/risk ratio from AHSCT.

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Funding

This work is financially supported by the National Natural Science Foundation of China (grant 81671233).

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Author notes

  1. Fangfang Ge and Hong Lin contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Tangdu Hospital, the Fourth Military Medical University, Xi’an, Shaanxi Province, People’s Republic of China

    Fangfang Ge, Hong Lin, Zhuyi Li & Ting Chang

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  1. Fangfang Ge
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  2. Hong Lin
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Contributions

C.T and G.F.F performed the study selection, data extraction, statistical analysis, and drafted the manuscript. All authors participated in study design, revised the protocol, contributed to interpretation of the results, critically revised the manuscript for important intellectual content, and read and approved the final version of this manuscript.

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Correspondence to Ting Chang.

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Figure A1

Forest plot for disease activity-free survival in each study and pooled estimates (PNG 146 kb)

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(TIF 23638 kb)

Figure A2

Forest plot for overall mortality in each study and pooled estimates (PNG 283 kb)

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(TIF 28961 kb)

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Ge, F., Lin, H., Li, Z. et al. Efficacy and safety of autologous hematopoietic stem-cell transplantation in multiple sclerosis: a systematic review and meta-analysis. Neurol Sci 40, 479–487 (2019). https://doi.org/10.1007/s10072-018-3670-1

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