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The purpose of this study is to identify clinical and genetic factors that may predict which children are at risk for creatinine increase and prolonged MTX clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>\n                      We conducted a single\u2010center, retrospective cohort study of pediatric patients with ALL who received 4000\u20135000\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      of MTX. Measurements We performed germline genotyping to determine genetic ancestry and allele status for 49 single nucleotide polymorphisms (SNPs) identified from the literature as related to MTX disposition. Bayesian hierarchical ordinal regression models for creatinine increase and for prolonged MTX clearance were developed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Results<\/jats:title>\n                    <jats:p>\n                      Hispanic ethnicity, body mass index (BMI)\u2009&lt;\u20093%, BMI between 85%\u201395%, and Native American genetic ancestry were found to be associated with an increased risk for creatinine elevation. Older age, Black race, and use of the intensive monitoring protocol were associated with a decreased risk for creatinine elevation. Older age, B\u2010 compared to T\u2010ALL, and the minor alleles of rs2838958\/\n                      <jats:italic>SLC19A1<\/jats:italic>\n                      and rs7317112\/\n                      <jats:italic>ABCC4<\/jats:italic>\n                      were associated with an increased risk for delayed clearance. Black race, MTX dose reduction, and the minor allele of rs2306283\/\n                      <jats:italic>SLCO1B1<\/jats:italic>\n                      were found to be associated with a decreased risk for delayed clearance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These predictors of MTX toxicities may allow for more precise individualized toxicity risk prediction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.2779","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T20:38:31Z","timestamp":1676061511000},"page":"205-214","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Novel and replicated clinical and genetic risk factors for toxicity from high\u2010dose methotrexate in pediatric acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-906X","authenticated-orcid":false,"given":"Mark","family":"Zobeck","sequence":"first","affiliation":[{"name":"Pediatrics, Hematology\/Oncology 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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