Clinical and Demographic Factors Contributing to Asparaginase-Associated Toxicities in Children With Acute Lymphoblastic Leukemia

Authors

Priyadarshani Dharia
Michael D Swartz
M Brooke Bernhardt
Han Chen
M Monica Gramatges
Philip J Lupo
Austin L Brown
Michael E Scheurer

Publication Date

12-1-2022

Journal

Leukemia & Lymphoma

DOI

10.1080/10428194.2022.2102621

PMID

35895075

PMCID

PMC9745725

PubMedCentral® Posted Date

12-1-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Adolescent, Child, Child, Preschool, Female, Humans, Infant, Male, Young Adult, Antineoplastic Agents, Asparaginase, Demography, Hyperbilirubinemia, Hypersensitivity, Overweight, Pancreatitis, Polyethylene Glycols, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Venous Thromboembolism, Asparaginase Toxicity, Hypersensitivity, Hyperbilirubinemia, Pancreatitis, Venous Thromboembolism

Abstract

A total of 548 patients (age range: 1-22 years, 60.4% Hispanic, 55.8% male) diagnosed with acute lymphoblastic leukemia were reviewed for pegaspargase-associated hypersensitivity (14.8%), hyperbilirubinemia (9.7%), venous thromboembolism (VTE, 9.7%), and pancreatitis (5.3%). Odds ratios (OR) and 95% confidence intervals (CI) evaluated associations between clinical factors and each toxicity, cumulative number of toxicities, and toxicity clusters identified using k-mode analysis. Most (68.9%) did not experience any toxicity, 24.6% experienced one toxicity, and 6.3% two or more. Age >10 years was associated with hyperbilirubinemia (OR = 3.83; 95% CI: 1.64-8.95), pancreatitis (OR = 3.72; 95% CI: 1.29-10.68), VTE (OR = 4.65; 95% CI: 1.96-11.02), and cumulative toxicity burden (OR = 3.28, 95% CI: 1.97-5.47); high-risk therapy with hypersensitivity (OR 2.25; 95% CI 1.25-4.05); and overweight with cumulative toxicity burden (OR = 1.76, 95% CI: 1.20-2.57). Eight unique toxicity profiles were identified. Older age, overweight, and treatment intensity contribute to pegaspargase-associated toxicities.