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A novel measure, designated Severe Toxicity-free survival (STFS), was developed through international consensus to integrate the most severe, symptomatic organ toxicities in outcome evaluation. This measure has not been applied to real-world data before. We assessed the incidence of 21 predefined Severe Toxicities in a nationwide cohort of 506 ALL patients aged 1\u201345 years treated according to the NOPHO ALL2008 protocol. At five years, event-free survival was 84.4% (95% CI: 81.3\u201387.7%) and Severe Toxicity-event-free survival was 78.4% (95% CI: 74.9\u201382.1%), with significantly lower values in adults (aged 18\u201345 years) than children (61.6% [52.6\u201372.2%] vs 82.4% [78.8\u201386.2%]; log-rank\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). The most common Severe Toxicities were severe osteonecrosis limiting activities of daily function (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200920) and disabling paralytic and neuropathic conditions (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200916). Exploratory analyses showed that 10\u201317-year-olds had the highest risk of Severe Toxicities similar to that of adults. These findings highlight a burden of severe, long-term toxicities in ALL survivors overlooked by traditional outcome measures, also following frontline therapy only. STFS should be incorporated in future trials for meaningful outcome evaluation and international comparisons across treatment strategies.\n                  <\/jats:p>","DOI":"10.1038\/s41375-026-02873-x","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T12:53:14Z","timestamp":1770727994000},"page":"630-637","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Severe toxicity-free survival following acute lymphoblastic leukemia in patients aged 1\u201345 years: a Danish cohort study"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7866-6185","authenticated-orcid":false,"given":"Camilla Grud","family":"Nielsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodil","family":"Als-Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3902-3694","authenticated-orcid":false,"given":"Birgitte Klug","family":"Albertsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d3lafur Birgir","family":"Dav\u00eddsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0125-1886","authenticated-orcid":false,"given":"Andreja","family":"Dimitrijevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4436-6798","authenticated-orcid":false,"given":"Henrik","family":"Hjalgrim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Ifversen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Lundgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8584-5920","authenticated-orcid":false,"given":"Line Stensig","family":"Lynggaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrik Malthe","family":"Overgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0578-3887","authenticated-orcid":false,"given":"Cecilie Utke","family":"Rank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7533-3112","authenticated-orcid":false,"given":"Mathias","family":"Rathe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6220-9414","authenticated-orcid":false,"given":"Klaus","family":"Rostgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0829-4993","authenticated-orcid":false,"given":"Kjeld","family":"Schmiegelow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3437-8338","authenticated-orcid":false,"given":"Liv","family":"Andr\u00e9s-Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"2873_CR1","doi-asserted-by":"publisher","first-page":"e306","DOI":"10.1016\/S2352-3026(19)30050-X","volume":"6","author":"DA Mulrooney","year":"2019","unstructured":"Mulrooney DA, Hyun G, Ness KK, Bhakta N, Pui CH, Ehrhardt MJ, et al. 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