Levocarnitine for pegaspargase-induced hepatotoxicity in older children and young adults with acute lymphoblastic leukemia.

Autor: Schulte R; Division of Pediatric Hematology and Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Hinson A; Division of Pediatric Hematology and Oncology, Levine Children's Atrium Health, Charlotte, North Carolina, USA., Huynh V; Division of Pediatric Oncology, University of California Irvine College of Medicine, CHOC Children's Hospital, Orange, California, USA., Breese EH; Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center/University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Pierro J; 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., Rotz S; Department of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, Pediatric Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA., Mixon BA; Department of Pediatrics, University of Tennessee College of Medicine Chattanooga and Children's Hospital at Erlanger, Chattanooga, Tennessee, USA., McNeer JL; Section of Pediatric Hematology, Oncology, and Stem Cell Transplant, University of Chicago Comer Children's Hospital, Chicago, Illinois, USA., Burke MJ; Division of Pediatric Hematology/Oncology and Blood and Marrow Transplantation, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., Orgel E; Cancer and Blood Disease Institute, Children's Hospital Los Angeles/University of Southern California, Los Angeles, California, USA.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2021 Nov; Vol. 10 (21), pp. 7551-7560. Date of Electronic Publication: 2021 Sep 16.
DOI: 10.1002/cam4.4281
Abstrakt: Background: Pegaspargase (PEG-ASP) 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-ASP-associated hepatotoxicity.
Methods: We collected data for patients age ≥10 years 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) >3 mg/dl. Secondary endpoints were transaminases >10× the upper limit of normal and any Grade ≥3 hepatotoxicity.
Results: Fifty-two patients received levocarnitine for prophylaxis (n = 29) or rescue (n = 32) 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-ASP. 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 >3 mg/dl (OR 0.12, p = 0.029). There was no difference between groups in CTCAE Grade ≥3 hepatotoxicity. C.bili >3 mg/dl during induction was associated with lower event-free survival.
Conclusions: This real-world data on levocarnitine supplementation during ALL induction highlights the risk of PEG-ASP-associated 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.
(© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: