{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:33:57Z","timestamp":1789011237827,"version":"build-2803163510"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["1129189"],"award-info":[{"award-number":["1129189"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000924","name":"Multiple Sclerosis Australia","doi-asserted-by":"publisher","award":["19-800"],"award-info":[{"award-number":["19-800"]}],"id":[{"id":"10.13039\/501100000924","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000924","name":"Multiple Sclerosis Australia","doi-asserted-by":"publisher","award":["22-2-103"],"award-info":[{"award-number":["22-2-103"]}],"id":[{"id":"10.13039\/501100000924","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100026269","name":"MS Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100026269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In the treatment of relapsing-remitting multiple sclerosis, autologous haematopoietic stem cell transplant (AHSCT) and immune-reconstitution therapies show several similarities. These treatment strategies have not yet been compared head-to-head. This study emulated pairwise trials of comparative effectiveness of stem cell transplant versus immune-reconstitution therapies cladribine and alemtuzumab.<\/jats:p>\n                  <jats:p>This cohort\/registry study of comparative treatment effectiveness included data from seven specialist multiple sclerosis centres with AHSCT programmes (RESCUE-MS) and international MSBase registry during 2006\u20132023. The study included patients with relapsing-remitting multiple sclerosis treated with AHSCT, cladribine or alemtuzumab, with a minimum of 2-months follow-up before commencing study therapy and \u22652 disability assessments after commencing the study therapy. Patients were matched on a propensity score derived from their clinical and demographic characteristics. The matched groups were compared according to annualized relapse rates, freedom from relapses and 6-month confirmed disability worsening and improvement (measured with the Expanded Disability Status Scale).<\/jats:p>\n                  <jats:p>The matching of 143 (stem cell) to 283 cladribine-treated patients and 134 (stem cell) to 562 alemtuzumab-treated patients reduced the measured differences between the groups by 98% and 96%, respectively. The matched patients had high mean disease activity (&amp;gt;0.8 relapses in the prior 2\u2005years), mean Expanded Disability Status Scale scores of 3\u20134, and were followed-up for a mean of 3.8\u20133.9 (stem cell), 1.9 (cladribine) or 4.5\u2005years (alemtuzumab). Compared with cladribine, stem cell transplant was associated with a lower risk of relapse [mean annualized relapse rate \u00b1 standard deviation (SD): 0.05 \u00b1 0.28 versus 0.16 \u00b1 0.39, respectively; hazard ratio: 0.24; 95% confidence interval (CI): 0.15\u20130.41], similar risk of disability worsening (hazard ratio: 0.70; 95% CI: 0.34\u20131.43) and higher probability of disability improvement (hazard ratio: 2.19; 95% CI: 1.31\u20133.66). Compared with alemtuzumab, stem cell transplant was associated with a lower risk of relapses (mean annualized relapse rate \u00b1 SD: 0.04 \u00b1 0.23 versus 0.09 \u00b1 0.21, respectively; hazard ratio: 0.52; 95% CI: 0.29\u20130.93), similar risk of disability worsening (hazard ratio: 0.95; 95% CI: 0.53\u20131.72) and higher probability of disability improvement (hazard ratio: 2.03; 95% CI: 1.23\u20133.34). Thirty-four per cent of patients treated with stem cell transplant experienced delayed complications, mainly infections. No treatment-associated deaths were reported.<\/jats:p>\n                  <jats:p>Among patients with active relapsing-remitting multiple sclerosis and moderate disability, AHSCT is superior to cladribine and alemtuzumab at suppressing relapses and enabling recovery of neurological function. The high effectiveness of stem cell transplant is likely attributable to a complex interplay between immune suppression and reconstitution.<\/jats:p>","DOI":"10.1093\/brain\/awaf286","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T12:02:12Z","timestamp":1754049732000},"page":"951-962","source":"Crossref","is-referenced-by-count":6,"title":["Haematopoietic stem cell transplant versus immune-reconstitution therapy in relapsing multiple sclerosis"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3778-1376","authenticated-orcid":false,"given":"Tomas","family":"Kalincik","sequence":"first","affiliation":[{"name":"Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital , Melbourne 3000 ,","place":["Australia"]},{"name":"CORe, Department of Medicine, University of Melbourne , Melbourne 3000 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sifat","family":"Sharmin","sequence":"additional","affiliation":[{"name":"Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital , Melbourne 3000 ,","place":["Australia"]},{"name":"CORe, Department of Medicine, University of Melbourne , Melbourne 3000 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0371-3666","authenticated-orcid":false,"given":"Izanne","family":"Roos","sequence":"additional","affiliation":[{"name":"Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital , Melbourne 3000 ,","place":["Australia"]},{"name":"CORe, Department of Medicine, University of Melbourne , Melbourne 3000 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S","family":"Freedman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Ottawa , Ottawa , K1N 6N5","place":["Canada"]},{"name":"Ottawa Hospital Research Institute , Ottawa , K1H 8L6","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold","family":"Atkins","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute , Ottawa , K1H 8L6","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Massey","sequence":"additional","affiliation":[{"name":"Department of Neurology, St Vincent's Hospital Sydney , Sydney 2010 ,","place":["Australia"]},{"name":"St Vincent\u2019s Clinical School, University of New South Wales , Sydney 2010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Sutton","sequence":"additional","affiliation":[{"name":"Department of Neurology, St Vincent's Hospital Sydney , Sydney 2010 ,","place":["Australia"]},{"name":"University of Sydney , Sydney 2006 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Withers","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s Clinical School, University of New South Wales , Sydney 2010 ,","place":["Australia"]},{"name":"Department of Haematology, St Vincent's Hospital Sydney , Sydney 2010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7045-1806","authenticated-orcid":false,"given":"Joachim","family":"Burman","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Neurology, Uppsala University , Uppsala 752 37 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8ivind","family":"Torkildsen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Haukeland University Hospital , Bergen 5009 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"B\u00f8","sequence":"additional","affiliation":[{"name":"Department of Neurology, Haukeland University Hospital , Bergen 5009 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Kristine","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Department of Haematology, Haukeland University Hospital , Bergen 5009 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Kubala","family":"Havrdova","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital , Prague 128 08 ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Krasulova","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital , Prague 128 08 ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Trneny","sequence":"additional","affiliation":[{"name":"Department of Haematology, First Faculty of Medicine, Charles University in Prague and General University Hospital , Prague 128 08 ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Kozak","sequence":"additional","affiliation":[{"name":"Department of Haematology, 3rd Faculty of Medicine, Charles University in Prague, and University Hospital Kralovske Vinohrady , Prague 100 34 ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Macdonell","sequence":"additional","affiliation":[{"name":"Department of Neurology, Austin Health , Melbourne 3084 ,","place":["Australia"]},{"name":"Department of Medicine, University of Melbourne , Melbourne 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J William L","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge CB2 1TN ,","place":["UK"]},{"name":"Department of Neurology, Addenbrooke\u2019s Hospital , Cambridge CB2 0QQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4738-0760","authenticated-orcid":false,"given":"Alasdair","family":"Coles","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge CB2 1TN ,","place":["UK"]},{"name":"Department of Neurology, Addenbrooke\u2019s Hospital , Cambridge CB2 0QQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke","family":"van der Walt","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Alfred Hospital , Melbourne 3004 ,","place":["Australia"]},{"name":"Department of Neuroscience, School of Translational Medicine, Monash University , Melbourne 3800 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Butzkueven","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Alfred Hospital , Melbourne 3004 ,","place":["Australia"]},{"name":"Department of Neuroscience, School of Translational Medicine, Monash University , Melbourne 3800 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Van Wijmeersch","sequence":"additional","affiliation":[{"name":"University MS Centre , Hasselt-Pelt 3900 ,","place":["Belgium"]},{"name":"Noorderhart, Rehabilitation & MS, Pelt and Hasselt University , Hasselt 3500 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Maria Delle Croci Hospital of Ravenna , Ravenna 48100 ,","place":["Italy"]},{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila , L\u2019Aquila 67100 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Surcinelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, MS Center, Neurology Unit, S. Maria Delle Croci Hospital of Ravenna , Ravenna 48100 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Neri","sequence":"additional","affiliation":[{"name":"AUSL Romagna, Department of Diagnostic Imaging, S. 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