Autologous Hematopoietic Stem Cell Transplantation in the Treatment of Multiple Sclerosis: The Beginning of a New Era?

Abstract

Autologous hematopoietic stem cell transplantation (AHSCT) has been gaining prominence over the last 20 years in the context of autoimmune diseases, particularly multiple sclerosis. This procedure allows the eradication of the autoreactive immune system and its subsequent reconstitution from hematopoietic stem cells, constituting a process of “immune reinitiation” by diversifying the T-cell repertoire and restoring its regulatory network, reducing the interleukin-17 response and normalizing the expression of microRNAs and gene expression profiles. Increasing evidence suggests that AHSCT can fully suppress disease activity in 70%-92% of cases at 2 years, a higher rate than current approved therapies. Its efficacy has also been demonstrated in brain atrophy, serum and cerebrospinal fluid biomarkers, cognition, fatigue and quality of life. With increasing experience and protocol development, the risks of the procedure have been decreasing to levels that are considered acceptable. Early adverse events such as organ toxicities, cytopenias, and infections, are the most common but in the long term, the possibility of secondary autoimmunity and malignancy have been described. In the most recent studies, treatment-related mortality is estimated at 0.2%. Maximum efficacy is seen in younger patients with shorter disease duration, fewer comorbidities and evidence of very active or treatment-refractory disease. Thus, AHSCT emerges as a new treatment alternative in MS, in specialized centers that ensure adequate protocol selection and correct patient follow-up to optimize its safety. This review, based on studies published between 2016 and 2021, which included 20 or more patients, aims to clarify and systematize the existing information on AHSCT both in terms of the underlying mechanisms of action, existing procedures and protocols, as well as associated benefits and risks.