{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:53:34Z","timestamp":1761008014519,"version":"build-2065373602"},"reference-count":39,"publisher":"BMJ","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2025,7,21]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Treatment of progression independent of relapse activity (PIRA) is a relevant unmet need in multiple sclerosis (MS), being only modestly affected by disease-modifying treatments (DMTs) which target predominantly adaptive immunity in the periphery. As chemotherapy administered during autologous haematopoietic stem cell transplantation (AHSCT) is bioavailable within the central nervous system (CNS), the hypothesis that AHSCT could affect long-term PIRA was explored in aggressive relapsing-remitting (RR)-MS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Retrospective propensity-score matched study including RR-MS patients who received BEAM\/ATG AHSCT or started natalizumab (NTZ, ie, controls) at our centre in Florence in the period 2007\u20132018. Main outcome: cumulative proportion of patients with PIRA during NTZ treatment epoch (ie, censoring controls at NTZ discontinuation) and whole follow-up (NTZ-other[o]DMTs, that is, including switch from NTZ to alternative DMTs).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty RR-MS were included in each group; median follow-up duration was 106 (6\u2013209) months. NTZ was discontinued by 29\/30 patients, who subsequently started alternative DMTs. Cumulative proportion of patients with PIRA did not differ between the two groups during the NTZ treatment epoch (p=0.990), but it was lower in AHSCT-treated compared with NTZ-oDMTs treated patients over the whole follow-up, being 10% vs 21% at year 5, and 10% versus 49% at year 10, respectively (p=0.020). AHSCT was superior to NTZ on relapses and NEDA-3, and to NTZ-oDMTs on all the secondary outcomes analysed. Baseline age and Expanded Disability Status Scale independently predicted PIRA in the whole cohort.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Timely treatment with AHSCT or DMTs targeting inflammation in both the peripheral and CNS compartments might prevent long-term PIRA in aggressive RR-MS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jnnp-2025-336808","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T17:20:32Z","timestamp":1760980832000},"page":"jnnp-2025-336808","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Autologous haematopoietic stem cell transplantation affects long-term progression independent of relapse activity in aggressive multiple sclerosis: a comparative matched 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Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Boncompagni","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital Careggi, Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Covicchio","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Barilaro","sequence":"additional","affiliation":[{"name":"Emergency Neurology Department, University Hospital Careggi, Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Cutini","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital Careggi, Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Di 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