Language
English
Publication Date
11-25-2025
Journal
Blood Advances
DOI
10.1182/bloodadvances.2025016978
PMID
40829116
PMCID
PMC12663015
PubMedCentral® Posted Date
8-21-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Hepatotoxicity is a well-documented complication of induction chemotherapy for acute lymphoblastic leukemia (ALL), but our understanding of its biological mechanisms is limited. We identified 314 patients with ALL (aged 1-19 years) treated at Texas Children’s Hospital (2008-2019) with diagnostic bone marrow plasma available for metabolomic profiling: 234 for discovery and 80 for replication. Hepatotoxicity during induction was defined as follows: (1) transaminitis: grade ≥3 aspartate aminotransferase or alanine aminotransferase or (2) conjugated hyperbilirubinemia: conjugated bilirubin (c.bili) >3 mg/dL. Untargeted profiling detected 519 metabolites. Adjusted odds ratios (aORs) for each metabolite were calculated with logistic regression, accounting for sex, age, body mass index, race/ethnicity, and treatment intensity. The population was 56% Latino, 57% male, 92% B-ALL, 25% overweight/obese, and 57% National Cancer Institute standard-risk at a median age of 5 years. Transaminitis was observed in 34% of the discovery and 24% of the replication cohort. Seven instances of c.bili >3 mg/dL were observed in the discovery cohort, with none in the replication cohort. Furthermore, 12 metabolites were associated with transaminitis (P < .05) in the discovery cohort, including 2 that replicated (P < .05): 1,2-dipalmitoyl-glycerophosphocholine (GPC) (aOR combined = 1.88 [95% confidence interval [CI], 1.26-2.79], P = .002) and 1-(1-enyl-palmitoyl)-2-palmitoleoyl-GPC (aOR combined = 1.56 [95% CI: 1.17-2.09], P = .003). In the discovery cohort, 34 metabolites were associated with c.bili >3 mg/dL, including the top association of 1,2-dipalmitoyl-GPC (aOR = 5.76 [95% CI: 2.20-23.16], P = .002). We observed and replicated associations between phosphatidylcholine metabolites at ALL diagnosis and hepatotoxicity during induction therapy, suggesting a potential role for lipid dysregulation in the development of hepatotoxicity.
Keywords
Humans, Male, Child, Female, Adolescent, Child, Preschool, Infant, Metabolomics, Chemical and Drug Induced Liver Injury, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Young Adult, Metabolome, Induction Chemotherapy
Published Open-Access
yes
Recommended Citation
Mason, Emily J; Crain, Anna M; Scheurer, Michael E; et al., "An Analysis of Diagnostic Metabolomic Profiles Associated With Hepatotoxicity During Childhood All Induction Therapy" (2025). Faculty, Staff and Students Publications. 6365.
https://digitalcommons.library.tmc.edu/baylor_docs/6365
Graphical Abstract