{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:12:43Z","timestamp":1791277963529,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The Acute Lymphoblastic Leukemia InterContinental (ALL\u2010IC) Study Group exemplifies the potential of broad international collaboration. Patient outcomes have improved by standardizing therapeutic options and employing flow cytometry\u2010based minimal residual disease (MRD) for treatment stratification. Nevertheless, relapse occurs in 10%\u201320% of cases, with survival rates falling short of benchmarks set by top\u2010tier published studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We aimed to unify treatment guidelines for children with first relapse of ALL across the ALL\u2010IC network, analyze post\u2010relapse outcomes, and report findings from an observational registry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients were stratified as standard\u2010risk (SR) or high\u2010risk (HR) based on relapse features and genetics. HR criteria included T\u2010cell immunophenotype, very early or early isolated bone marrow relapse, and relapse post\u2010stem cell transplant (SCT). SR was assigned to all others. SCT was indicated in the whole HR group and in SR patients with poor responses (MRD\u00a0\u2265\u00a00.1% on Day 29).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 370 patients (mean age 9 years; 33.2% female) diagnosed with first relapse between 2017 and 2021, 90.5% had received ALL\u2010IC\u2010Berlin\u2010Frankfurt\u2010M\u00fcnster (BFM) 2009 treatment initially. Upon relapse, 46.8% were classified as SR and 53.2% as HR. Complete remission rates post\u2010induction were 84% (SR) and 56% (HR). MRD\u00a0&lt;\u00a00.1% was achieved by 53% (SR) and 29% (HR). Five\u2010year overall survival was 50.5% (74% SR, 32% HR). HR outcomes were hindered by disease progression, treatment toxicity, and posttransplant complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This inaugural ALL\u2010IC REL Consortium report demonstrates promising SR outcomes, akin to the International Study for the Treatment of Childhood Relapsed ALL (IntReALL) findings, but highlights poor HR outcomes with standard chemotherapy. Novel therapeutic strategies are urgently needed in upcoming ALL\u2010IC\u2010BFM REL protocols.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.32063","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T09:32:10Z","timestamp":1759483930000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bridging the Gap in Pediatric Relapsed Acute Lymphoblastic Leukemia Treatment: Insights and Outcomes From the ALL\u2010IC REL 2016 Guidelines"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4949-1344","authenticated-orcid":false,"given":"Marko","family":"Kavcic","sequence":"first","affiliation":[{"name":"University Children's Hospital University Medical Centre Ljubljana Slovenia"},{"name":"Faculty of Medicine University of Ljubljana  Vrazov trg, Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1niel J.","family":"Erd\u00e9lyi","sequence":"additional","affiliation":[{"name":"Semmelweis University Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1407-2334","authenticated-orcid":false,"given":"Volkan","family":"Hazar","sequence":"additional","affiliation":[{"name":"Memorial Health Group Medstar Yildiz Hospital Antalya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-7883","authenticated-orcid":false,"given":"Mirella","family":"Ampatzidou","sequence":"additional","affiliation":[{"name":"\u201cAGIA SOPHIA\u201d Childrens\u2019 Hospital Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6314-1386","authenticated-orcid":false,"given":"Boryana","family":"Avramova","sequence":"additional","affiliation":[{"name":"University Hospital \u201cTzaritza Joanna\u201d Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6031-8190","authenticated-orcid":false,"given":"Anca","family":"Colita","sequence":"additional","affiliation":[{"name":"Fundeni Clinical Institute Bucharest Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Makiya","sequence":"additional","affiliation":[{"name":"Hospital Italiano de Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9716-9264","authenticated-orcid":false,"given":"Sophia","family":"Polychronopoulou","sequence":"additional","affiliation":[{"name":"\u201cAGIA SOPHIA\u201d Childrens\u2019 Hospital Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6548-2429","authenticated-orcid":false,"given":"Bence","family":"H\u0151b\u00f6r","sequence":"additional","affiliation":[{"name":"Semmelweis University Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1132-2131","authenticated-orcid":false,"given":"Tomaz","family":"Prelog","sequence":"additional","affiliation":[{"name":"University Children's Hospital University Medical Centre Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Reyes","sequence":"additional","affiliation":[{"name":"Hospital Robert de Rio Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Tordecilla","sequence":"additional","affiliation":[{"name":"Clinica Santa Maria Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3454-9870","authenticated-orcid":false,"given":"Koray","family":"Yal\u00e7in","sequence":"additional","affiliation":[{"name":"Bahcesehir University Medical Park Goztepe Hospital Istanbul 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Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.32063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T12:49:57Z","timestamp":1765975797000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.32063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,3]]},"references-count":19,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/pbc.32063"],"URL":"https:\/\/doi.org\/10.1002\/pbc.32063","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,3]]},"assertion":[{"value":"2025-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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