RESUMEN
Over the last two decades, haematopoietic stem cell transplantation (HSCT) has been explored as a potential therapeutic strategy for autoimmune diseases refractory to conventional treatments, including neurological disorders. Although both autologous (AHSCT) and allogeneic HSCT (allo-HSCT) were investigated, AHSCT was preferentially developed due to a more favourable safety profile compared to allo-HSCT. Multiple sclerosis (MS) represents the most frequent neurological indication for AHSCT, but increasing evidence on the potential effectiveness of transplant in other autoimmune neurological diseases is emerging, although with a risk-benefit ratio overall more uncertain than in MS. In the present work, the rationale for the use of HSCT in neurological diseases and the experimental models that prompted its clinical application will be briefly covered. Case series and prospective studies exploring the use of HSCT in autoimmune diseases other than MS will be discussed, covering both frequent and rare neurological disorders such as myasthenia gravis, myopathies, and stiff-person syndrome. Finally, an updated summary of ongoing and future studies focusing on this issue will be provided.
RESUMEN
BACKGROUND AND PURPOSE: Effectiveness of autologous haematopoietic stem cell transplantation (AHSCT) in relapsing-remitting multiple sclerosis (MS) is well known, but in secondary-progressive (SP)-MS it is still controversial. Therefore, AHSCT activity was evaluated in SP-MS using low-dose immunosuppression with cyclophosphamide (Cy) as a comparative treatment. METHODS: In this retrospective monocentric 1:2 matched study, SP-MS patients were treated with intermediate-intensity AHSCT (cases) or intravenous pulses of Cy (controls) at a single academic centre in Florence. Controls were selected according to baseline characteristics adopting cardinality matching after trimming on the estimated propensity score. Kaplan-Meier and Cox analyses were used to estimate survival free from relapses (R-FS), survival free from disability progression (P-FS), and no evidence of disease activity 2 (NEDA-2). RESULTS: A total of 93 SP-MS patients were included: 31 AHSCT, 62 Cy. Mean follow-up was 99 months in the AHSCT group and 91 months in the Cy group. R-FS was higher in AHSCT compared to Cy patients: at Year 5, 100% versus 52%, respectively (p < 0.0001). P-FS did not differ between the groups (at Year 5: 70% in AHSCT and 81% in Cy, p = 0.572), nor did NEDA-2 (p = 0.379). A sensitivity analysis including only the 31 "best-matched" controls confirmed these results. Three neoplasms (2 Cy, 1 AHSCT) and two fatalities (2 Cy) occurred. CONCLUSIONS: This study provides Class III evidence, in SP-MS, on the superior effectiveness of AHSCT compared to Cy on relapse activity, without differences on disability accrual. Although the suppression of relapses was observed in the AHSCT group only, AHSCT did not show advantages over Cy on disability, suggesting that in SP-MS disability progression becomes based more on noninflammatory neurodegeneration than on inflammation.