{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:00:59Z","timestamp":1789970459136,"version":"4.0.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Metachromatic leukodystrophy (MLD) is a progressive neurometabolic disease which can be treated with hematopoietic stem cell transplantation (HSCT). With emerging therapies like gene therapy, understanding the effectiveness of HSCT in late-onset forms has become increasingly important. Late-onset forms are rare, and the limited evidence on eligibility and outcomes complicates treatment decisions. The aim was to compare the long-term outcomes of the largest European cohort of HSCT-treated and untreated late-juvenile and adult MLD patients.<\/jats:p>\n                  <jats:p>In this observational multi-center registry-based study, retrospective and prospective data from the MLD initiative registry were used. Late-onset patients with a confirmed diagnosis from nine European centers were included. We analysed clinical and patient-reported outcomes. Patients were grouped by symptom status at diagnosis, and we performed visual outcome assessment and regression analysis.<\/jats:p>\n                  <jats:p>Fifteen pre-symptomatic HSCT-treated patients were compared with 37 early or advanced symptomatic HSCT-treated, and 79 untreated late-onset MLD patients. Patients were followed for up to 25 years after diagnosis, with median follow-ups of 14.5 (5.1\u201317.9), 5.6 (2.8\u201312.5) and 9.0 (3.3\u201317.1) years and median ages at follow-up of 30.0 (23.6\u201335.0), 23.5 (18.0\u201330.8), and 27.8 (17.7\u201340.0) for pre-symptomatic HSCT, symptomatic HSCT, and untreated patients, respectively. Advanced disease stage (ADS) was observed in 4\/15 (27%) of pre-symptomatic HSCT, 29\/37 (78%) symptomatic HSCT, and 57\/79 (72%) of untreated patients (p=0.004). HSCT appears to delay ADS (HR 1.49 95%CI 0.96-2.30) and improves quality-of-life and daily life functioning measures.<\/jats:p>\n                  <jats:p>HSCT has a positive effect on the course of the disease, especially in pre-symptomatic patients, but cannot always prevent the progression of symptoms. Quality-of-life improves across all stages of the disease, with pre-symptomatic treatment yielding the greatest benefits. These findings emphasize the importance of early diagnosis and intervention. This study may inform treatment decisions and provides an evidence base for future comparison with innovative therapies.<\/jats:p>","DOI":"10.1093\/brain\/awag323","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:22:24Z","timestamp":1789672944000},"source":"Crossref","is-referenced-by-count":0,"title":["Allogeneic haematopoietic stem cell transplantation in late-onset metachromatic leukodystrophy"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1601-7379","authenticated-orcid":false,"given":"Daphne H","family":"Schoenmakers","sequence":"first","affiliation":[{"name":"Department of Child Neurology, Emma\u2019s Children\u2019s Hospital, Amsterdam UMC location Vrije Universiteit , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Leukodystrophy Center, Amsterdam Neuroscience, Cellular & Molecular Mechanisms , 1105 AZ Amsterdam ,","place":["The Netherlands"]},{"name":"Medicine for Society, Platform at Amsterdam UMC location University of Amsterdam , 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mareen R","family":"Datema","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC location University of Amsterdam , 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-6784","authenticated-orcid":false,"given":"Shanice","family":"Beerepoot","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Emma\u2019s Children\u2019s Hospital, Amsterdam UMC location Vrije Universiteit , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Leukodystrophy Center, Amsterdam Neuroscience, Cellular & Molecular Mechanisms , 1105 AZ Amsterdam ,","place":["The Netherlands"]},{"name":"Princess M\u00e1xima Center for Pediatric Oncology , 3584 CS, Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije A B C","family":"Asbreuk","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Emma\u2019s Children\u2019s Hospital, Amsterdam UMC location Vrije Universiteit , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Leukodystrophy Center, Amsterdam Neuroscience, Cellular & Molecular Mechanisms , 1105 AZ Amsterdam ,","place":["The Netherlands"]},{"name":"Medicine for Society, Platform at Amsterdam UMC location University of Amsterdam , 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline G","family":"Bergner","sequence":"additional","affiliation":[{"name":"Leukodystrophy Center, Department of Neurology, University Hospital Leipzig , 04103 Leipzig ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Awi\u00dfus","sequence":"additional","affiliation":[{"name":"Leukodystrophy Center, Department of Neurology, University Hospital Leipzig , 04103 Leipzig ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Bley","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, University Medical Center Hamburg Eppendorf , 20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Sigel","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, University Medical Center Hamburg Eppendorf , 20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janna","family":"Bredow","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, University Medical Center Hamburg Eppendorf , 20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Calbi","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) , 20132 Milan ,","place":["Italy"]},{"name":"Pediatric Immuno-Hematology Unit, IRCCS Ospedale San Raffaele , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Fumagalli","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) , 20132 Milan ,","place":["Italy"]},{"name":"Pediatric Immuno-Hematology Unit, IRCCS Ospedale San Raffaele , 20132 Milan ,","place":["Italy"]},{"name":"Unit of Neurology, IRCCS-Ospedale San Raffaele , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Inverso","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) , 20132 Milan ,","place":["Italy"]},{"name":"Pediatric Immuno-Hematology Unit, IRCCS Ospedale San Raffaele , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik A","family":"Eklund","sequence":"additional","affiliation":[{"name":"Pediatrics, Clinical Sciences, Lund University , 221 85 Lund ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine W","family":"Gr\u00f8nborg","sequence":"additional","affiliation":[{"name":"Center for Inherited Metabolic Diseases, Copenhagen University Hospital Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Pediatrics and Adolescent Medicine and Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wietske H M","family":"Grol","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Emma\u2019s Children\u2019s Hospital, Amsterdam UMC location Vrije Universiteit , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Leukodystrophy Center, Amsterdam Neuroscience, Cellular & Molecular Mechanisms , 1105 AZ Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Medical Psychology, Amsterdam Neuroscience , Amsterdam UMC, 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilie","family":"Videb\u00e6k","sequence":"additional","affiliation":[{"name":"Center for Inherited Metabolic Diseases, Copenhagen University Hospital Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Pediatrics and Adolescent Medicine and Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Kehrer","sequence":"additional","affiliation":[{"name":"Neuropediatrics, General Pediatrics, Diabetology, Endocrinology and Social Pediatrics, University of T\u00fcbingen, University Hospital T\u00fcbingen , 72016, T\u00fcbingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8912-0954","authenticated-orcid":false,"given":"Marjo S","family":"van der Knaap","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Emma\u2019s Children\u2019s Hospital, Amsterdam UMC location Vrije Universiteit , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Leukodystrophy Center, Amsterdam Neuroscience, Cellular & Molecular Mechanisms , 1105 AZ Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit , 1081 HV Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Schnermann","sequence":"additional","affiliation":[{"name":"Neuropediatrics, General Pediatrics, Diabetology, Endocrinology and Social Pediatrics, University of T\u00fcbingen, University Hospital T\u00fcbingen , 72016, T\u00fcbingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Rosewich","sequence":"additional","affiliation":[{"name":"Neuropediatrics, General Pediatrics, Diabetology, Endocrinology and Social Pediatrics, University of T\u00fcbingen, University Hospital T\u00fcbingen , 72016, T\u00fcbingen ,","place":["Germany"]},{"name":"Center for Rare Diseases, University of T\u00fcbingen , 72072 T\u00fcbingen ,","place":["Germany"]},{"name":"Department of Pediatric Neurology, University Children's Hospital G\u00f6ttingen , 37075 G\u00f6ttingen ,","place":["Germany"]},{"name":"German Center for Child and Adolescent Health (DZKJ), partner site G\u00f6ttingen , 37075 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7737-2142","authenticated-orcid":false,"given":"Peter","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of hematology\/oncology children\u00b4s university hospital, University of T\u00fcbingen , 72076 T\u00fcbingen ,","place":["Germany"]},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site T\u00fcbingen , 72072 T\u00fcbingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M","family":"van Hasselt","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases, University Medical Center Utrecht , 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline A","family":"Lindemans","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology , 3584 CS, Utrecht ,","place":["The Netherlands"]},{"name":"Department of Pediatric Hematopoietic Stem Cell Transplantation, UMC Utrecht and Princess Maxima Center , 3584 CS Utrecht ,","place":["The Netherlands"]},{"name":"Regenerative Medicine Institute, University Medical Center Utrecht , 3584 CT Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moniek","family":"de Witte","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Medical Center Utrecht , 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Langeveld","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC location University of Amsterdam , 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludger","family":"Sch\u00f6ls","sequence":"additional","affiliation":[{"name":"Department of Neurology and Hertie-Institute for Clinical Brain Research, University of T\u00fcbingen , 72076 T\u00fcbingen ,","place":["Germany"]},{"name":"German Center of Neurodegenerative Diseases (DZNE), \u00a0 72076 T\u00fcbingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap Jan","family":"Boelens","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Transplant and Cellular Therapies, Memorial Sloan Kettering Cancer Center , New York, NY 10065 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4ivi","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and adolescent Medicine, Division of paediatric Neurology, Oulu University Hospital , 90220 Oulu ,","place":["Finland"]},{"name":"Research Unit of Clinical Medicine, University of Oulu , 90220 Oulu ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Uusimaa","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and adolescent Medicine, Division of paediatric Neurology, Oulu University Hospital , 90220 Oulu ,","place":["Finland"]},{"name":"Research Unit of Clinical Medicine, University of Oulu , 90220 Oulu ,","place":["Finland"]},{"name":"Medical Research Center, University of Oulu and Oulu University Hospital , 90220 Oulu ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Mochel","sequence":"additional","affiliation":[{"name":"Reference Center for Adult Leukodystrophy, Department of Medical Genetics, Sorbonne University, Paris Brain Institute, La Piti\u00e9-Salp\u00eatri\u00e8re University Hospital , 75013 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Sevin","sequence":"additional","affiliation":[{"name":"Reference Center for Leukodystrophies, Pediatric Neurology Department, H\u00f4pital Bic\u00eatre, Le Kremlin Bic\u00eatre , 94270 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla E M","family":"Hollak","sequence":"additional","affiliation":[{"name":"Medicine for Society, Platform at Amsterdam UMC location University of Amsterdam , 1105 AZ Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC location University of Amsterdam , 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Groeschel","sequence":"additional","affiliation":[{"name":"Neuropediatrics, General Pediatrics, Diabetology, Endocrinology and Social Pediatrics, University of T\u00fcbingen, University Hospital T\u00fcbingen , 72016, T\u00fcbingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1721-0728","authenticated-orcid":false,"given":"Nicole I","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Emma\u2019s Children\u2019s Hospital, Amsterdam UMC location Vrije Universiteit , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Leukodystrophy Center, Amsterdam Neuroscience, Cellular & Molecular Mechanisms , 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,21]]},"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awag323\/71243569\/awag323.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awag323\/71243569\/awag323.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:19:42Z","timestamp":1789967982000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/advance-article\/doi\/10.1093\/brain\/awag323\/8819743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/brain\/awag323","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]},"article-number":"awag323"}}