A pilot trial of autologous hematopoietic stem cell transplant in neuromyelitis optic spectrum disorder

•NMOSD is a profoundly disabling disease with limited treatment options that have historically been relatively toxic, but it is defined almost solely by relapses (so relapse mitigation is essentially disability mitigation).•While there has been an advent of targeted, newer treatments, these still require long-term use and appear to be best suited to Aquaporin-4 antibody positive patients.•Autologous hematopoietic stem cell transplantation (AHSCT) has been highly successful in MS and we hypothesized that it would be effective in select patients with NMOSD.•AHSCT using rituximab as part of the regimen was trialed in three patients with NMO/NMOSD, showing moderate to marked disease improvement in two patients up to 10 years post-transplant.•The AHSCT regimen best suited to NMOSD is still a work in progress, and may require a more intense regimen than the rituximab-based one studied, but it has the potential to truly impact disability in the long-term. Autologous hematopoietic stem cell transplantation (AHSCT) has become a standard treatment in multiple sclerosis. The role of AHSCT for neuromyelitis optica spectrum disorder (NMO/NMOSD) is unclear. We studied AHSCT in NMO/NMOSD patients who have failed conventional immunosuppressive therapy. Eligible patients received AHSCT with cyclophosphamide, rabbit antithymocyte globulin, and rituximab and followed for ≥ five years. The primary outcome was relapse-free status at year three. Additional outcomes included relapse status at year five, relapse rate, EDSS, MRI activity, and overall survival. Between 2010-2016, three patients were enrolled. One patient has had no evidence of disease activity over 10 years, one had improvement in relapse rate and EDSS but did have a breakthrough clinically and radiologically requiring rituximab at year five, and the third died at year 3.5 due to uncontrollable NMOSD relapses and accumulation of marked disability. In our trial, AHSCT appeared safe, and moderately effective with two of three patients showing improvement in disease activity and disability. Future studies should be undertaken to determine the ideal AHSCT conditioning and the characteristics of patients likely to enter long-term remission.