Autologous Stem Cell Transplantation for Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune, inflammatory, and neurodegenerative disorder of the central nervous system, likely generated by an Epstein-Barr virus infection with auto-antibodies targeting myelin antigens primarily through molecular mimicry. MS may have a relapsing-remitting (RRMS) course or can be primary progressive. A proportion of patients may evolve to secondary progressive disease, with progressive debilitation. While disease-modifying therapies (DMTs) have remained the mainstay for treatment of MS, many patients continue to experience disease activity and increased debilitation on these treatments. Autologous hematopoietic stem cell transplantation (AHSCT), although much less utilized, has emerged as an effective therapeutic option for DMT-resistant RRMS, offering sustained remission in most patients with RRMS, and preventing further debilitation with improvement in neurological outcomes. AHSCT has had mixed results in patients with progressive disease. Overall, studies indicate that AHSCT can achieve higher rates of no evidence of disease activity compared with DMTs, a lower annualized relapse rate, and potential slowing of progressive disease with very low treatment-related mortality. This review summarizes the current evidence for the role of AHSCT in the treatment of this disease, with a focus on timing for transplantation, transplant outcomes, and conditioning regimens used prior to transplantation. Further research is needed to define optimal patient selection, optimal conditioning regimens used prior to transplantation, and eventually compare outcomes with chimeric antigen receptor T-cell therapy-a new form of targeted B-cell therapy-if it proves to be similarly effective in treating this disease.