{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T18:07:57Z","timestamp":1789927677651,"version":"4.0.1"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T00:00:00Z","timestamp":1668211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006058","name":"St. Baldrick's Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006058","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Obesity at diagnosis of childhood acute lymphoblastic leukemia (ALL) is associated with greater risk of relapse; whether this association extends to obesity during maintenance is unstudied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study used data from AALL03N1 to calculate median body mass index (BMI) for 676 children over 6 consecutive months during maintenance therapy; BMI percentile (BMI%ile) were operationalized as normal\/underweight (&lt;85%ile), overweight\/obese (85%\u201398%ile), and extreme obesity (\u226599%ile). Hazard of relapse was estimated using multivariable proportional subdistributional hazards regression after adjusting for all relevant demographic and clinical predictors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Median age at study enrollment was 6 years and median length of follow\u2010up was 7.9\u00a0years. Overall, 43.3% of the cohort was underweight\/normal weight, 44.8% was overweight\/obese, and 11.8% had extreme obesity. Cumulative incidence of relapse at 4 years from study enrollment was higher among those with extreme obesity (13.6%\u00a0\u00b1\u00a04.5%) compared to those with underweight\/normal weight (9.0%\u00a0\u00b1\u00a02.1%). Multivariable analysis revealed that children with extreme obesity had a 2.4\u2010fold (95% confidence interval [CI], 1.1\u20135.0; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.01) greater hazard of relapse compared to those who were underweight\/normal weight. Overweight\/obese patients were at comparable risk to those who were underweight\/normal weight (hazard ratio, 0.8; 95% CI, 0.4\u20131.6). Erythrocyte thioguanine nucleotide (TGN) levels were significantly lower among children with extreme obesity compared to those with underweight\/normal weight (141.6 vs. 168.8 pmol\/8\u00a0\u00d7\u00a010<jats:sup>8<\/jats:sup> erythrocytes; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.0002), however, the difference in TGN levels did not explain the greater hazard of relapse among those with extreme obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Extreme obesity during maintenance therapy is associated with greater hazard of relapse in children with ALL. Underlying mechanisms of this association needs further investigation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Lay summary<\/jats:title><jats:p>\n<jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Findings from this study demonstrate that extreme obesity during maintenance therapy is associated with a greater hazard of relapse among children with acute lymphoblastic leukemia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show that children with obesity have lower levels of erythrocyte thioguanine nucleotides even after adjusting for adherence to oral chemotherapy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>However, these lower levels do not explain the greater hazard of relapse, paving the way for future studies to explore this association.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.34529","type":"journal-article","created":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T03:10:29Z","timestamp":1668222629000},"page":"151-160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Body mass index during maintenance therapy and relapse risk in children with acute lymphoblastic leukemia: A\u00a0Children's Oncology Group report"],"prefix":"10.1002","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3245-2218","authenticated-orcid":false,"given":"Aman","family":"Wadhwa","sequence":"first","affiliation":[{"name":"Institute for Cancer Outcomes and Survivorship University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Division of Pediatric Hematology\/Oncology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute for Cancer Outcomes and Survivorship University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Hageman","sequence":"additional","affiliation":[{"name":"Institute for Cancer Outcomes and Survivorship University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5878-5523","authenticated-orcid":false,"given":"Anna L.","family":"Hoppmann","sequence":"additional","affiliation":[{"name":"Institute for Cancer Outcomes and Survivorship University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Division of Pediatric Hematology\/Oncology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Angiolillo","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Children's National Medical Center  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Dickens","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen","family":"Lew","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Children's Healthcare of Atlanta Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"Neglia","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology University of Minnesota Masonic Children's Hospital  Minnesota Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaddanapudi","family":"Ravindranath","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology Children's Hospital of Michigan  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Kim","family":"Ritchey","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Termuhlen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Minnesota Medical School  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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