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As there are no strategies for predicting patients who will require CDPG<jats:sub>2<\/jats:sub>, we evaluated the role of demographic, clinical, and genetic factors for CPDG<jats:sub>2<\/jats:sub> use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Cases who received CPDG<jats:sub>2<\/jats:sub> and controls who did not were identified by chart review of acute lymphoblastic leukemia (ALL) patients who received MTX doses between 1000 and 5000\u00a0mg\/m<jats:sup>2<\/jats:sup> between 2010 and 2017. We used multivariable Bayesian logistic regression to evaluate the association of CPDG<jats:sub>2<\/jats:sub> use with demographic and clinical variables and, on a subset of patients, with genetic ancestry and 49 single nucleotide variants previously associated with MTX toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 423 patients who received 1592 doses of MTX. Of the 18 patients who received CPDG<jats:sub>2<\/jats:sub>, 17 (94%) were Hispanic. No patients who received 1000 or 2000\u00a0mg\/m<jats:sup>2<\/jats:sup> of MTX received CPDG<jats:sub>2<\/jats:sub>. Hispanic ethnicity (odds ratio: 4.68; 95% compatibility interval: 1.63\u201315.06) and older age (1.87 [1.17\u20133.17]) were associated with receiving CPDG<jats:sub>2<\/jats:sub>. Of the 177 patients in the genomic cohort, 11 received CPDG<jats:sub>2<\/jats:sub>. Each additional G allele of rs7317112 in <jats:italic>ABCC4<\/jats:italic> increased the odds of requiring CPDG<jats:sub>2<\/jats:sub> (3.10 [1.12\u20136.75]). Six other loci (<jats:italic>NTRK1<\/jats:italic>\/rs10908521, <jats:italic>TSG1\/<\/jats:italic>rs9345389, <jats:italic>STT3B\/<\/jats:italic>rs1353327, <jats:italic>SCLO1B1<\/jats:italic>\/rs4149056, <jats:italic>GATA3\/<\/jats:italic>rs3824662, <jats:italic>ARID5B\/<\/jats:italic>rs10821936) demonstrated probabilities of association between 88% and 97%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrated that demographic characteristics, including Hispanic ethnicity and age, are associated with CPDG<jats:sub>2<\/jats:sub> use. Additionally, we provide evidence that inherited genetic variation is associated with risk of requiring CPDG<jats:sub>2<\/jats:sub>. If validated in independent populations, this information could be leveraged to develop targeted toxicity prevention strategies for children with ALL.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29036","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T13:45:05Z","timestamp":1617198305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Novel risk factors for glucarpidase use in pediatric acute lymphoblastic leukemia: Hispanic ethnicity, age, and the <i>ABCC4<\/i> gene"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-906X","authenticated-orcid":false,"given":"Mark C.","family":"Zobeck","sequence":"first","affiliation":[{"name":"Baylor College of Medicine and Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9612-3624","authenticated-orcid":false,"given":"M. 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