Autologous hematopoietic stem cell transplantation versus low-dose immunosuppression in secondary-progressive multiple sclerosis

Background: 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: Retrospective monocentric 1:2 matched study in SP-MS patients treated with BEAM-AHSCT (cases) or IV 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), disability progression (P-FS) and NEDA-2. Results: 93 SP-MS were included: 31 AHSCT, 62 Cy. Mean follow-up: 99 months in the AHSCT and 91 months in the Cy groups. R-FS was higher in AHSCT compared to Cy patients: at year 5, 100% vs 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 the 31 "best-matched" controls only confirmed these results. Three neoplasms (2 Cy, 1 AHSCT) and two fatalities (2 Cy) occurred. Conclusion: 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. Despite 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 more based on non-inflammatory neurodegeneration than on inflammation.