Multiple sclerosis (MS) is the most common non-traumatic disabling disease to affect young adults. The incidence of the disease is increasing worldwide, together with the socioeconomic impact of the disease. The underlying cause of MS and mechanisms behind this increase remain opaque, although complex gene-environment interactions may play a significant role. The epidemiology of MS indicates that infection with the Epstein-Barr virus, vitamin D deficiency, smoking, childhood obesity and others may have a role in disease development. Treatments for MS have increased exponentially in number, efficacy, and risk (Muraro et al., 2017) Autologous hematopoietic stem cell transplantation (aHSCT) has been identified as the most effective treatment for persons with MS (Patti et al., 2022), the rationale to conduct this procedure is the so called “re-booting” of the immune system aimed to ameliorate the immune-mediated inflammation and damage of the central nervous system structures (Dobson and Giovannoni, 2019). We have developed a method to conduct aHSCT in persons with MS and have shown its feasibility (Ruiz-Argüelles et al., 2017), safety (Gale et al., 2019) and usefulness (Ruiz-Argüelles et al., 2019) in a cohort of more than 1300 persons with the disease. We (Olivares-Gazca et al., 2022) and others (Mohammadi et al., 2021) have shown that the overall response rate of persons with MS given aHSCT is around 80%, as assessed by the change on the patient-reported outcomes (PROs) of the expanded disability status scale (EDSS) score (Signori et al., 2020), this figure being substantially better than that obtained employing several novel immunosuppressive drugs. When aHSCT was initally conducted in MS, 26 years ago (Bose and Freedman, 2021), it was thought that the procedure should be considered only after the failure of the response to other lines of treatments (Dargahi et al., 2017). Even though immunosuppressive therapy in MS is known as disease-modifying therapy (DMT), it seems clear that aHSCT is the only treatment which can change the natural history of the disease, since it is a more profound way of inducing immunosuppression. To analyze if aHSCT should be done early in the course of the disease or after failing to other therapies, we have studied the long-term results of aHSCT in a cohort of persons with MS who were given, or not, immunosuppressive drugs before the transplant.