The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described.

Background and purpose Natalizumab (NTZ) is a highly effective treatment for relapsing‐remitting multiple sclerosis (MS), but its withdrawal is often followed by disease reactivation or rebound, even if other disease‐modifying treatments (DMTs) are administered. In this study, for the first time, the safety and efficacy of autologous hematopoietic stem‐cell transplantation (aHSCT) performed following NTZ discontinuation were retrospectively compared with conventional DMTs. Methods Patients with relapsing‐remitting MS treated with NTZ who discontinued the drug after at least six administrations and with at least 6 months of follow‐up were included. Patients underwent aHSCT after a minimum of 6 months following NTZ withdrawal, receiving meanwhile cyclophosphamide or corticosteroids, or other DMTs approved for MS (control group) after an adequate wash‐out period. Both hematological and neurological follow‐up were assessed according to standard policies. Results A total of 52 patients were included, 11 who received aHSCT and 41 who received DMTs. Baseline clinical and demographic characteristics were similar between the two groups. No fatality or life‐threatening complications, including progressive multifocal leukoencephalopathy, were observed. At 3 years following NTZ discontinuation, no evidence of disease activity was reported in 54.5% of the patients in the aHSCT group compared with 11.5% of those in the DMT group (P = 0.0212). Disease reactivation in the patients with aHSCT was observed only during wash‐out/bridging therapy and 100% of the cases were free from disease activity after aHSCT. Conclusions These data suggest that an aggressive therapy should be established after NTZ with the shortest possible wash‐out period. aHSCT after 6 months from NTZ withdrawal appears to be safe.

Background: Autologous haematopoietic stem cell transplantation (aHSCT) is a valuable option in aggressive relapsing–remitting multiple sclerosis (MS), but its efficacy in secondary progressive (SP)-MS is still controversial. Objective: Assessing efficacy of aHSCT in SP-MS by clinical-radiological outcomes. Methods: Open-label monocentric retrospective study enrolling consecutive SP-MS patients treated with BEAM-aHSCT in the period 1999–2016. Results: In total, 26 SP-MS patients with moderate–severe disability were included. Progression-free survival (PFS) at years 5 and 10 after aHSCT were, respectively, 42% and 30%. Out of 16 patients who worsened, only 6 patients (23% overall) maintained continuous disability accrual (CDA), whereas 10 patients stabilized following one single-step Expanded Disability Status Scale (EDSS) worsening. CDA-free survival was 74% at 5–10 years. No relapses or magnetic resonance imaging (MRI) activity were reported, thus no evidence of disease activity (NEDA)-3 corresponded to PFS. Annualized rate of brain atrophy (AR-BVL) normalized after 1 year in 55% of the cases analysed (12/22). Conclusion: BEAM-aHSCT halted CDA and normalized AR-BVL in most of the treated patients, inducing long-term remission of inflammatory activity at a median follow-up of 99 months (range 27–222). These data suggest that CDA might still be mainly driven by inflammation in a subgroup of SP-MS and could therefore be reversed by treatments. CDA should be analysed independently from any isolated disability worsening.

No abstract