Pegaspargase-related high-grade hepatotoxicity in a pediatric-inspired adult acute lymphoblastic leukemia regimen does not predict recurrent hepatotoxicity with subsequent doses Journal Article

  

Authors:	Burke, P. W.; Aldoss, I.; Lunning, M. A.; Devlin, S. M.; Tallman, M. S.; Pullarkat, V.; Mohrbacher, A. M.; Douer, D.
Article Title:	Pegaspargase-related high-grade hepatotoxicity in a pediatric-inspired adult acute lymphoblastic leukemia regimen does not predict recurrent hepatotoxicity with subsequent doses
Abstract:	Pediatric acute lymphoblastic leukemia (ALL) regimens, including higher cumulative asparaginase doses, have been investigated in adult ALL to improve outcomes. Preliminary results are promising, but hepatotoxicity rates with long-acting pegaspargase are greater in adults than children. However, adult pegaspargase-related hepatotoxicity is not as clearly defined despite being the commonest adult toxicity. We studied the frequency and characteristics of high-grade pegaspargase-related hepatotoxicity in newly diagnosed adults on a pediatric-inspired regimen that included six planned pegaspargase doses, 2000 IU/m2/dose intravenously, with doses given at least four weeks apart and not discontinued or dose-reduced for previous hepatotoxicity. Pegaspargase-related toxicity was monitored weekly after 185 delivered doses and reported by NCI CTCAE v3.0. Fifty-one patients, aged 18–57, received 192 pegaspargase doses (3.8 doses/patient). High-grade hyperbilirubinemia occurred in 16 (31.4%) patients and 23 (12.4%) doses; high-grade transaminitis occurred in 33 (64.7%) patients and 62 (33.5%) doses. Of 11 patients with high-grade hyperbilirubinemia who received at least one subsequent pegaspargase dose, six (54.5%) experienced recurrent toxicity; of 24 patients with high-grade transaminitis who received at least one subsequent pegaspargase dose, 15 (62.5%) developed recurrent toxicity. Pegaspargase at this dose and interval is associated with high hepatotoxicity rates, but patients can be rechallenged despite earlier pegaspargase-related hepatotoxicity. © 2018 Elsevier Ltd
Keywords:	adult; controlled study; major clinical study; drug efficacy; drug safety; controlled clinical trial; infection; liver toxicity; multiple cycle treatment; phase 2 clinical trial; deep vein thrombosis; prediction; acute lymphoblastic leukemia; fever; adverse outcome; pancreatitis; therapy delay; clinical research; disease duration; hyperbilirubinemia; hypertriglyceridemia; induction chemotherapy; hepatotoxicity; hypertransaminasemia; all; characteristics; asparaginase macrogol; human; male; female; priority journal; article; pegaspargase
Journal Title:	Leukemia Research
Volume:	66
ISSN:	0145-2126
Publisher:	Elsevier Ltd
Date Published:	2018-03-01
Start Page:	49
End Page:	56
Language:	English
DOI:	10.1016/j.leukres.2017.12.013
PROVIDER:	scopus
PUBMED:	29407583
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85041487652&doi=10.1016%2fj.leukres.2017.12.013&partnerID=40&md5=66387a94ce8a54cd39e9f1ecddc59217
Notes:	Article -- Export Date: 1 March 2018 -- Source: Scopus

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