{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:18:17Z","timestamp":1787876297157,"version":"build-2784847793"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>The ALL SCTped 2012 FORUM (For Omitting Radiation Under Majority age) trial compared outcomes for children \u22654 years of age transplanted for acute lymphoblastic leukaemia (ALL) who were randomised to myeloablation with a total body irradiation (TBI)-based or chemotherapy-based conditioning regimen. The TBI-based preparation was associated with a lower rate of relapse compared with chemoconditioning. Nevertheless, the age considered suitable for TBI was progressively raised over time to spare the most fragile youngest patients from irradiation-related complications. The best approach to use for children &amp;lt;4 years of age remains unclear. Children diagnosed with ALL in their first year of life, defined as infants, have a remarkably poorer prognosis compared with older children. This is largely explained by the biology of their ALL, with infants often carrying a <jats:italic>KMT2A<\/jats:italic> gene rearrangement, as well as by their fragility. In contrast, the clinical presentations and biological features of ALL in children &amp;gt;1 year but &amp;lt;4 years often resemble those presented by older children. In this review, we explore the state of the art regarding haematopoietic stem cell transplantation (HSCT) in children &amp;lt;4 years, the preparative regimens available, and new developments in the field that may influence treatment decisions.<\/jats:p>","DOI":"10.3389\/fped.2022.807992","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T17:32:24Z","timestamp":1645723944000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Acute Lymphoblastic Leukaemia in the Youngest: Haematopoietic Stem Cell Transplantation and Beyond"],"prefix":"10.3389","volume":"10","author":[{"given":"Adriana","family":"Balduzzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Buechner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Ifversen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Hugues","family":"Dalle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca M.","family":"Colita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Bierings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1056\/NEJMra1400972","article-title":"Acute lymphoblastic leukemia in children","volume":"373","author":"Hunger","year":"2015","journal-title":"N Engl J Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.3390\/jcm10091926","article-title":"Advances in the diagnosis and treatment of pediatric acute lymphoblastic leukemia","volume":"10","author":"Inaba","year":"2021","journal-title":"J Clin Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1038\/bmt.2016.139","article-title":"Incidence and severity of crucial late effects after allogeneic HSCT for malignancy under the age of 3 years: TBI is what really matters","volume":"51","author":"Bresters","year":"2016","journal-title":"Bone Marrow Transplant."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/j.bbmt.2017.04.017","article-title":"Survival and late effects after allogeneic hematopoietic cell transplantation for hematologic malignancy at less than three years of age","volume":"23","author":"Vrooman","year":"2017","journal-title":"Biol Blood Marrow Transplant."},{"key":"B5","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1111\/bjh.16279","article-title":"Changes in neurocognitive function and central nervous system structure in childhood acute lymphoblastic leukaemia survivors after treatment: a meta-analysis","volume":"188","author":"Zhou","year":"2020","journal-title":"Br J Haematol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1200\/JCO.20.02529","article-title":"Total body irradiation or chemotherapy conditioning in childhood ALL: a multinational, randomized, noninferiority Phase III study","volume":"39","author":"Peters","year":"2021","journal-title":"J Clin Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1002\/pbc.24132","article-title":"Modifications to induction therapy decrease risk of early death in infants with acute lymphoblastic leukemia treated on Children's Oncology Group P9407","volume":"59","author":"Salzer","year":"2012","journal-title":"Pediatr Blood Cancer."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1182\/blood.2019004741","article-title":"A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial","volume":"136","author":"Tomizawa","year":"2020","journal-title":"Blood."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e28624","DOI":"10.1002\/pbc.28624","article-title":"No benefit of interfant protocols compared to BFM-based protocols for infants with acute lymphoblastic leukemia. 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