Relapse risk and outcome of discontinuing asparaginase in children with acute lymphoblastic leukemia

Asparaginase is a cornerstone of pediatric acute lymphoblastic leukemia (ALL) therapy, but treatment discontinuation due to toxicity may increase relapse risk and compromise outcomes. We retrospectively analyzed 993 pediatric ALL patients (aged 1.0-17.9 years) treated under the CCCG-ALL-2015 protocol from May 2015 to October 2020. Patients were followed from the last administered asparaginase dose until relapse, death, secondary malignancy (SMN), or end of follow-up (median: 6.0 years). Asparaginase was truncated in 40 (4.0%) patients, primarily due to hypersensitivity or pancreatitis. Compared to non-truncated patients (n = 953), truncated patients had a higher 6-year cumulative incidence of relapse (CIR: 31.5% vs. 17.5%, HR: 2.01, P = .038), as well as inferior event-free survival (EFS) (HR: 2.11, P = .015) and overall survival (OS) (HR: 2.74, P = .046). CIR was also significantly higher among patients receiving < 53% of planned asparaginase doses (32.1% vs. 14.0%, HR: 2.71, P = .004). In intermediate-risk subgroup, truncation was associated with significantly reduced EFS (HR: 1.95, P = .046). Older age (≥ 10 years), higher MRD levels (day 19 ≥ 0.1%), and higher asparaginase exposure percentage were predictors of discontinuation. In conclusion, asparaginase discontinuation is associated with inferior outcomes, emphasizing the importance of replacement with alternative formulations to maintain treatment intensity.