{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:07:00Z","timestamp":1787170020822,"version":"build-2736575974"},"reference-count":44,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"36","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2022,12,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Findings from St Jude Total Therapy Study 16 (Total 16) showed early intensification of triple intrathecal therapy (ITT) improved CNS disease control for children with newly diagnosed acute lymphoblastic leukemia (ALL) at the greatest risk of CNS relapse. We examined the impact of this treatment on end-of-therapy neurocognitive outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Between 2007 and 2017, 400 (83.5%) of 479 eligible patients treated with Total 16 risk-directed chemotherapy completed protocol-directed neurocognitive testing at the end of therapy. Intensified ITT was defined as \u2265 21 cumulative doses for patients with low-risk ALL (n = 70\/194) and \u2265 27 doses for those with standard-to-high risk ALL (n = 81\/206).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Compared with age-normative expectations, the overall group had significantly lower estimated intelligence quotient ( P &lt; .0001), attention ( P = .0051), working memory ( P = .0001), processing speed ( P = .0002), fine motor speed ( P = .0001), and math ( P = .0087). Caregiver ratings of patient functioning showed elevated risk for problems in attention ( P = .0173), executive function ( P = .0001), and adaptive skills ( P = .0001). Among the low-risk treatment group, there were no significant differences between patients treated with or without intensified ITT (all P's &gt;.10). Among patients with standard-to-high risk ALL, those treated with intensified ITT had poorer working memory ( P = .0328) and fine motor speed ( P = .0403), and elevated ratings of inattention ( P = .0189) and executive dysfunction ( P = .0245). In the standard-to-high risk group, females treated with intensified ITT had lower working memory scores. Public insurance status was associated with worse neurocognitive outcomes in both treatment groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Standard-to-high risk patients treated with intensified ITT are at moderately increased risk for neurocognitive problems. The findings suggest a threshold effect for ITT exposure, which can inform the design of future clinical trials and approaches to neurocognitive monitoring and intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.22.00263","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:00:31Z","timestamp":1667404831000},"page":"4218-4227","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":17,"title":["The Impact of Intensified CNS-Directed Therapy on Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated Without Cranial Irradiation"],"prefix":"10.1200","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2698-5816","authenticated-orcid":false,"given":"Lisa M.","family":"Jacola","sequence":"first","affiliation":[{"name":"Department of Psychology, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8931-4134","authenticated-orcid":false,"given":"Heather M.","family":"Conklin","sequence":"additional","affiliation":[{"name":"Department of Psychology, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0476-7001","authenticated-orcid":false,"given":"Kevin R.","family":"Krull","sequence":"additional","affiliation":[{"name":"Department of Psychology, St Jude Children's Research Hospital, Memphis, TN"},{"name":"Department of Epidemiology & Cancer Control, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deqing","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1054-1201","authenticated-orcid":false,"given":"Wilburn E.","family":"Reddick","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0303-5658","authenticated-orcid":false,"given":"Ching-Hon","family":"Pui","sequence":"additional","affiliation":[{"name":"Department of Oncology, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2835-5869","authenticated-orcid":false,"given":"Sima","family":"Jeha","sequence":"additional","affiliation":[{"name":"Department of Oncology, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","volume-title":"Cancer Facts & Figures","author":"American Cancer Society","year":"2021"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2013.06.007"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djs344"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.2315"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.02322"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2019.01027"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.3205"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(16)30283-8"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1002\/pon.3470"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.2174\/1573396314666181031134919"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.1002\/pon.4186"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.4149"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(02)00260-5"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30742"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.71.7587"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28913"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.1007\/s11764-018-0679-7"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01692"},{"key":"b19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900386"},{"key":"b20","volume-title":"Stanford-Binet Intelligence Scales","author":"Roid G","year":"2003","edition":"4"},{"key":"b21","volume-title":"Conners Kiddie Continuous Performance Test","author":"Conners CK","year":"2001","edition":"2"},{"key":"b22","volume-title":"Conners\u2019 Continuous Performance Test (CPT II v. 5)","author":"Conners CK","year":"2000","edition":"2"},{"key":"b23","volume-title":"Woodcock-Johnson Third Edition, Tests of Cognitive Abilities","author":"Mather N","year":"2001"},{"key":"b24","volume-title":"Wechsler Intelligence Scale for Children","author":"Wechsler D","year":"2004","edition":"4"},{"key":"b25","volume-title":"Wechsler Preschool and Primary Scales of Intelligence","author":"Wechsler D","year":"2002","edition":"3"},{"key":"b26","volume-title":"Wechsler Adult Intelligence Scale","author":"Wechsler D","year":"1997","edition":"3"},{"key":"b27","volume-title":"California Verbal Learning Test, Children's Version","author":"Fine EM","year":"1994"},{"key":"b28","volume-title":"California Verbal Learning Test","author":"Delis DC","year":"2000","edition":"2"},{"key":"b29","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-79948-3_207"},{"key":"b30","volume-title":"Tests of Academic Achievement","author":"Woodcock R","year":"2001","edition":"3"},{"key":"b31","volume-title":"Behavior Assessment System for Children (BASC-3)","author":"Reynolds CR","year":"2015","edition":"3"},{"key":"b32","volume-title":"Behavior Rating Inventory of Executive Function\u2014Preschool Version","author":"Greene JA","year":"2001"},{"key":"b33","volume-title":"Behavior Rating Inventory of Executive Function","author":"Gioia G","year":"2001"},{"key":"b34","volume-title":"Adaptive Behavior Assessment System","author":"Harrison PL","year":"2003","edition":"2"},{"key":"b35","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djaa136"},{"key":"b36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042486"},{"key":"b37","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2013.3139"},{"key":"b38","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24644"},{"key":"b39","first-page":"3","volume-title":"The Myelogenetic Cycles of Regional Maturation of the Brain","author":"Yakolev PI","year":"1967"},{"key":"b40","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0511(00)00051-X"},{"key":"b41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0216554"},{"key":"b42","doi-asserted-by":"publisher","DOI":"10.1089\/brain.2017.0574"},{"key":"b43","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25749"},{"key":"b44","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.02444"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.22.00263","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T18:00:52Z","timestamp":1671127252000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.22.00263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,20]]},"references-count":44,"journal-issue":{"issue":"36","published-print":{"date-parts":[[2022,12,20]]}},"alternative-id":["10.1200\/JCO.22.00263"],"URL":"https:\/\/doi.org\/10.1200\/jco.22.00263","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,20]]},"assertion":[{"value":"2022-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-15","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}