{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:19:41Z","timestamp":1789017581845,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["2KL2TR002457"],"award-info":[{"award-number":["2KL2TR002457"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001855\/UL1TR000130"],"award-info":[{"award-number":["UL1TR001855\/UL1TR000130"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["K12CA090625"],"award-info":[{"award-number":["K12CA090625"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pegaspargase (PEG\u2010ASP) is an integral component of therapy for acute lymphoblastic leukemia (ALL) but is associated with hepatotoxicity that may delay or limit future therapy. Obese and adolescent and young adult (AYA) patients are at high risk. Levocarnitine has been described as potentially beneficial for the treatment or prevention of PEG\u2010ASP\u2010associated hepatotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected data for patients age \u226510\u00a0years who received levocarnitine during induction therapy for ALL, compared to a similar patient cohort who did not receive levocarnitine. The primary endpoint was conjugated bilirubin (c.bili) &gt;3\u00a0mg\/dl. Secondary endpoints were transaminases &gt;10\u00d7 the upper limit of normal and any Grade \u22653 hepatotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty\u2010two patients received levocarnitine for prophylaxis (<jats:italic>n<\/jats:italic>\u00a0=\u00a029) or rescue (<jats:italic>n<\/jats:italic>\u00a0=\u00a032) of hepatotoxicity. Compared to 109 patients without levocarnitine, more patients receiving levocarnitine were obese and\/or older and had significantly higher values for some hepatotoxicity markers at diagnosis and after PEG\u2010ASP. Levocarnitine regimens varied widely; no adverse effects of levocarnitine were identified. Obesity and AYA status were associated with an increased risk of conjugated hyperbilirubinemia and severe transaminitis. Multivariable analysis identified a protective effect of levocarnitine on the development of c.bili &gt;3\u00a0mg\/dl (OR 0.12, <jats:italic>p\u00a0<\/jats:italic>=\u00a00.029). There was no difference between groups in CTCAE Grade \u22653 hepatotoxicity. C.bili &gt;3\u00a0mg\/dl during induction was associated with lower event\u2010free survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This real\u2010world data on levocarnitine supplementation during ALL induction highlights the risk of PEG\u2010ASP\u2010associated hepatotoxicity in obese and AYA patients, and hepatotoxicity's potential impact on survival. Levocarnitine supplementation may be protective, but prospective studies are needed to confirm these findings.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4281","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T07:15:57Z","timestamp":1631776557000},"page":"7551-7560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Levocarnitine for pegaspargase\u2010induced hepatotoxicity in older children and young adults with acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7869-9099","authenticated-orcid":false,"given":"Rachael","family":"Schulte","sequence":"first","affiliation":[{"name":"Division of Pediatric Hematology and Oncology Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Hinson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology Levine Children's Atrium Health Charlotte North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van","family":"Huynh","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology University of California Irvine College of Medicine CHOC Children's Hospital Orange California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin H.","family":"Breese","sequence":"additional","affiliation":[{"name":"Division of Oncology, Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center\/University of Cincinnati College of Medicine Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Pierro","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology NYU Grossman School of Medicine Perlmutter Cancer Center Hassenfeld Children's Hospital at NYU Langone Health New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2896-1113","authenticated-orcid":false,"given":"Seth","family":"Rotz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation Pediatric Institute Cleveland Clinic Foundation Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A.","family":"Mixon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Tennessee College of Medicine Chattanooga and Children's Hospital at Erlanger Chattanooga Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"McNeer","sequence":"additional","affiliation":[{"name":"Section of Pediatric Hematology, Oncology, and Stem 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