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While space\u2013time clustering of ALL cases has been suggested, only one prior study has examined clustering by genetic subtype. We investigated space\u2013time clustering of childhood ALL in Sweden, both overall and by genetic subtype. The cohort included 1,629 children age 0\u201318 years diagnosed with ALL between 1992 and 2017, comprising 1,446 B-cell precursor ALL (BCP-ALL) and 183 T-cell ALL (T-ALL) cases. Two BCP-ALL subgroups were analyzed: high hyperdiploidy (HeH,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009466) and\n                    <jats:italic>ETV6::RUNX1<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009225). The Unbiased Knox Test and Unbiased Combined Knox Test were used to assess space\u2013time clustering at the municipality level, accounting for multiple testing and population shifts. The Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm was applied to identify significant clusters. Logistic regression was used to evaluate demographic differences between clusters, including age, sex, and birth order. Significant space\u2013time clustering was observed in the HeH subgroup for both place and date of birth (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.005) and place and date of diagnosis (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.011), at space\u2013time thresholds of 40\u00a0km\/18 months and 30\u00a0km\/24 months, respectively. No clustering was detected in the overall BCP-ALL group, T-ALL group, or the\n                    <jats:italic>ETV6::RUNX1<\/jats:italic>\n                    subgroup. Space\u2013time clustering at birth and diagnosis was observed in the HeH subgroup, suggesting potential etiologic heterogeneity in BCP-ALL. These findings support further investigation of environmental and infectious exposures across immunophenotypes and genetic subtypes in larger cohorts.\n                  <\/jats:p>","DOI":"10.1007\/s10654-025-01323-9","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T05:03:30Z","timestamp":1768194210000},"page":"149-160","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Space\u2013time clustering of childhood high hyperdiploid B-cell precursor acute lymphoblastic leukemia: a nationwide Swedish study"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2072-7309","authenticated-orcid":false,"given":"Gleb","family":"Bychkov","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0219-9522","authenticated-orcid":false,"given":"Niklas","family":"Engsner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6907-4954","authenticated-orcid":false,"given":"Benedicte","family":"Bang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7637-1949","authenticated-orcid":false,"given":"Mats Marshall","family":"Heyman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3185-2962","authenticated-orcid":false,"given":"Gisela","family":"Barbany","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3034-9222","authenticated-orcid":false,"given":"Anna Skarin","family":"Nordenvall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-7219","authenticated-orcid":false,"given":"Giorgio","family":"Tettamanti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4571-9759","authenticated-orcid":false,"given":"Claes","family":"Stranneg\u00e5rd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3285-4281","authenticated-orcid":false,"given":"Ann","family":"Nordgren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"issue":"5","key":"1323_CR1","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1200\/JCO.2010.30.7405","volume":"29","author":"CH Pui","year":"2011","unstructured":"Pui CH, Carroll WL, Meshinchi S, Arceci RJ. 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