Clinical and demographic factors contributing to asparaginase-associated toxicities in children with acute lymphoblastic leukemia

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.

Keywords:

• Asparaginase toxicity
• hypersensitivity
• hyperbilirubinemia
• pancreatitis
• venous thromboembolism

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was supported in part by the National Institutes of Health National Cancer Institute [P20CA262733 and K07CA218362]; The Cancer Prevention Research Institute of Texas [RP160771 and RP170668]; The St. Baldrick’s Foundation Consortium Research Grant [522277]; Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium; Cancer Prevention and Research Institute of Texas and St. Baldrick's Foundation.