{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:50:55Z","timestamp":1790812255992,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T00:00:00Z","timestamp":1602633600000},"content-version":"am","delay-in-days":366,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T00:00:00Z","timestamp":1571011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["GM115279"],"award-info":[{"award-number":["GM115279"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CA142665"],"award-info":[{"award-number":["CA142665"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CA21765)"],"award-info":[{"award-number":["CA21765)"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Glucocorticoids and asparaginase, used to treat acute lymphoblastic leukemia (ALL), can cause hypertriglyceridemia. We compared triglyceride levels, risk factors, and associated toxicities in two ALL trials at St. Jude Children's Research Hospital with identical glucocorticoid regimens, but different asparaginase formulations. In Total XV (TXV), native\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      <jats:sc>l<\/jats:sc>\n                      \u2010asparaginase was front\u2010line therapy versus the pegylated formulation (PEG\u2010asparaginase) in Total XVI (TXVI).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedure<\/jats:title>\n                    <jats:p>\n                      Patients enrolled on TXV (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0498) and TXVI (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0598) were assigned to low\u2010risk (LR) or standard\/high\u2010risk (SHR) treatment arms (ClinicalTrials.gov identifiers: NCT00137111 and NCT00549848). Triglycerides were measured four times and were evaluable in 925 patients (TXV:\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0362; TXVI:\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0563). The genetic contribution was assessed using a triglyceride polygenic risk score (triglyceride\u2010PRS). Osteonecrosis, thrombosis, and pancreatitis were prospectively graded.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The largest increase in triglycerides occurred in TXVI SHR patients treated with dexamethasone and PEG\u2010asparaginase (4.5\u2010fold increase;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;1\u00a0\u00d7\u00a010\n                      <jats:sup>\u221215<\/jats:sup>\n                      ). SHR patients treated with PEG\u2010asparaginase (TXVI) had more severe hypertriglyceridemia (&gt;1000\u00a0mg\/dL) compared to native\n                      <jats:sc>l<\/jats:sc>\n                      \u2010asparaginase (TXV): 10.5% versus 5.5%, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.007). At week 7, triglycerides did not increase with dexamethasone treatment alone (LR patients) but did increase with dexamethasone plus asparaginase (SHR patients). The variability in triglycerides explained by the triglyceride\u2010PRS was highest at baseline and declined with therapy. Hypertriglyceridemia was associated with osteonecrosis (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.0006) and thrombosis (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.005), but not pancreatitis (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.4).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Triglycerides were affected more by PEG\u2010asparaginase than native\n                      <jats:sc>l<\/jats:sc>\n                      \u2010asparaginase, by asparaginase more than dexamethasone, and by drug effects more than genetics. It is not clear whether triglycerides contribute to thrombosis and osteonecrosis or are biomarkers of the toxicities.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.28040","type":"journal-article","created":{"date-parts":[[2019,10,15]],"date-time":"2019-10-15T00:08:50Z","timestamp":1571098130000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Asparaginase formulation impacts hypertriglyceridemia during therapy for acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"67","author":[{"given":"Emily R.","family":"Finch","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences St. Jude Children's Research Hospital  Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colton A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences St. Jude Children's Research Hospital  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