{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T21:02:12Z","timestamp":1794085332050,"version":"4.8.0"},"reference-count":40,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"25","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>The ALL10 protocol improved outcomes for children with ALL by stratifying and adapting therapy into three minimal residual disease\u2013defined risk groups: standard risk, medium risk (MR), and high risk. IKZF1-deleted ( IKZF1del) ALL in the largest MR group still showed poor outcome, in line with protocols worldwide, accounting for a high number of overall relapses. ALL10 showed high toxicity in Down syndrome (DS) and excellent outcome in ETV6::RUNX1 ALL. Poor prednisone responders (PPRs) were treated as high risk in ALL10. In ALL11, we prolonged therapy for IKZF1del from 2 to 3 years. We reduced therapy for DS by omitting anthracyclines completely, for ETV6::RUNX1 in intensification, and for PPR by treatment as MR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Eight hundred nineteen patients with ALL (age, 1-18 years) were enrolled on ALL11 and stratified as in ALL10. Results were compared with those in ALL10.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The five-year overall survival (OS), event-free survival (EFS), cumulative risk of relapse (CIR), and death in complete remission on ALL11 were 94.2% (SE, 0.9%), 89.0% (1.2), 8.2% (1.1), and 2.3% (0.6), respectively. Prolonged maintenance for IKZF1del MR improved 5-year CIR by 2.2-fold (10.8% v 23.4%; P = .035) and EFS (87.1% v 72.3%; P = .019). Landmark analysis at 2 years from diagnosis showed a 2.9-fold reduction of CIR (25.6%-8.8%; P = .008) and EFS improvement (74.4%-91.2%; P = .007). Reduced therapy did not abrogate 5-year outcome for ETV6::RUNX1 (EFS, 98.3%; OS, 99.4%), DS (EFS, 87.0%; OS, 87.0%), and PPR (EFS, 81.1%; OS, 94.9%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Children with IKZF1del ALL seem to benefit from prolonged maintenance therapy. Chemotherapy was successfully reduced for patients with ETV6::RUNX1, DS, and PPR ALL. It has to be noted that these results were obtained in a nonrandomized study using a historical control group.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.22.02705","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T16:57:13Z","timestamp":1689699433000},"page":"4130-4142","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":51,"title":["Improved Outcome for ALL by Prolonging Therapy for\n                    <i>IKZF1<\/i>\n                    Deletion and Decreasing Therapy for Other Risk Groups"],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nl3227","registry":"10.18810\/dutch-trial-register"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2997-3570","authenticated-orcid":false,"given":"Rob","family":"Pieters","sequence":"first","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"},{"name":"Dutch Childhood Oncology Group (DCOG), Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hester","family":"de Groot-Kruseman","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"},{"name":"Dutch Childhood Oncology Group (DCOG), Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5588-0277","authenticated-orcid":false,"given":"Marta","family":"Fiocco","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"},{"name":"Dutch Childhood Oncology Group (DCOG), Utrecht, the Netherlands"},{"name":"Department of Biomedical Data Science, Section Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands"},{"name":"Mathematical Institute, Leiden University, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"Verwer","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"},{"name":"Dutch Childhood Oncology Group (DCOG), Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merian","family":"Van Overveld","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Sonneveld","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"},{"name":"Dutch Childhood Oncology Group (DCOG), Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9457-3763","authenticated-orcid":false,"given":"Vincent","family":"van der Velden","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2280-7617","authenticated-orcid":false,"given":"H. Berna","family":"Beverloo","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Bierings","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"},{"name":"Dutch Childhood Oncology Group (DCOG), Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasja","family":"Dors","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0339-6816","authenticated-orcid":false,"given":"Val\u00e9rie","family":"de Haas","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"},{"name":"Dutch Childhood Oncology Group (DCOG), Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3012-6109","authenticated-orcid":false,"given":"Peter","family":"Hoogerbrugge","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5822-7668","authenticated-orcid":false,"given":"Inge","family":"Van der Sluis","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Tissing","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9503-0795","authenticated-orcid":false,"given":"Margreet","family":"Veening","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4848-7789","authenticated-orcid":false,"given":"Judith","family":"Boer","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5795-2921","authenticated-orcid":false,"given":"Monique","family":"Den Boer","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.6364"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003191"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018025718"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.199"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.056135"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.87"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808253"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.153023"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.275"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-10-462358"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.84"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.6115"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.00261"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(18)30173-X"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005224"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2712"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9469.2006.00529.x"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(96)00075-X"},{"key":"b19","first-page":"1141","volume":"16","author":"Gray RJ","year":"1988","journal-title":"Am Stat"},{"key":"b20","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1999.10474144"},{"key":"b21","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2021"},{"key":"b23","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v038.i07"},{"key":"b24","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.74.3617"},{"key":"b25","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(08)70339-5"},{"key":"b26","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.134"},{"key":"b27","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.154"},{"key":"b28","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007702"},{"key":"b29","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-112920"},{"key":"b30","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2973"},{"key":"b32","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(21)00272-6"},{"key":"b33","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0670-y"},{"key":"b34","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02292"},{"key":"b35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.08.025"},{"key":"b36","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-149443"},{"key":"b37","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-534347"},{"key":"b38","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27083"},{"key":"b39","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.2850"},{"key":"b40","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.29387"},{"key":"b41","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-532598"},{"key":"b42","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.44"}],"updated-by":[{"DOI":"10.1200\/jco.23.02556","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000}}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.22.02705","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T16:00:31Z","timestamp":1703001631000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.22.02705"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,1]]},"references-count":40,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2023,9,1]]}},"alternative-id":["10.1200\/JCO.22.02705"],"URL":"https:\/\/doi.org\/10.1200\/jco.22.02705","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742718054.793600004","asserted-by":"object"}]},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,1]]},"assertion":[{"value":"2022-12-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-30","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}