PEGging Down Risk Factors for Peg-asparaginase Hepatotoxicity in Patients with Acute Lymphoblastic Leukemia

Asparaginase is commonly de-emphasized/omitted in adult acute lymphoblastic leukemia regimens due to poor tolerability, including hepatotoxicity (HTX). Adult patients (n = 100) given induction therapy containing pegylated asparaginase (PEG) from January 2008 to February 2016 were evaluated for HTX. Sixteen patients met criteria for HTX (direct bilirubin >3 g/dL). A multivariable model identified body surface area >2m (OR 7.40; 95% CI: 1.73-31.61, p = .007), albumin <3 mg/dL (OR 4.62; 95% CI: 1.09-19.68, p = .038), and platelet count <50 K/mm (OR 9.36; 95% CI: 2.13-41.17, p = .003) as risk factors for HTX. More patients with HTX missed ≥1 dose of intended chemotherapy (75% vs. 8%, p < .001). In patients with HTX, complete response and 30-day mortality rates were 40% and 9% versus 73% and 1% in patients without HTX (p = .02 and p < .001). A risk scoring tool was created to predict risk of toxicity, which should be validated through a prospective evaluation.