Autologous hematopoietic stem cell transplantation is a treatment that has been suggested for a small group of patients with relapsing remitting multiple sclerosis where available medication has limited effect or causes serious side effects. In this Health Technology Assessment we have summarized and evaluated research of efficacy, safety, economic evaluations and ethical considerations related to autologous stem cell transplantation for multiple sclerosis. We did not identify any controlled study, with the exception of one very small randomized controlled trial with limited relevance. The other studies were one registry study and 21 smaller case series, of which eight mainly comprised relapsing-remitting multiple sclerosis. We assessed the quality of the evidence as low for mortality at 100 days, and very low for all other outcomes. There is considerable uncertainty linked to the results. We found that:

• mortality at 100 days after the treatment is possibly 2 percent or lower
• most patients experienced serious side effects related to immunosuppression and toxicity in the early stages (within 100 days), but it is not possible to give reliable estimates of their frequency
• serious adverse events such as infections, sepsis, other autoimmune diseases or heamorrhages in the later stages were common, but it is not possible to to give reliable estimates of their frequency
• the registry study and the patient series, which mainly comprised patients with relapsing remitting multiple sclerosis, reported that more than half of the patients remained stable or achieved an improvement up to three years after the treatment, but we do not know what the results would have been without autologous stem cell transplantation
• autologous stem cell transplantation costs approximately between 480,000 and 605,000 Norwegian kroner per patient in the intervention year, which corresponds to an annual budget impact of 3.9 million kroner, assuming that 15 patients are treated with autologous stem cell transplantation
• unpredictable disease progression and considerable uncertainty about benefit versus harm are the most important ethical challenges related to offering autologous stem cell transplantation for the treatment of individuals with multiple sclerosis

Well designed controlled studies that systematically investigate the effect and safety of HSCT compared to other relevant treatment are needed in order to clarify the treatment benefits. An ongoing randomized controlled trial with 120 enrolled patients, and five-year follow-up, is expected to be completed in 2021.