Risk factors and outcomes of asparaginase-associated pancreatitis in pediatric patients with ALL.

Asparaginase-associated pancreatitis (AAP) is a significant complication in acute lymphoblastic leukemia (ALL) therapy, often leading to treatment delays or discontinuation. This study aimed to identify AAP risk factors, assess outcomes after first and second episodes, and evaluate the impact of asparaginase rechallenge. We retrospectively analyzed 7,640 patients (aged 1 month-18 years) treated under the Chinese Children Cancer Group ALL 2015 protocol. Patients were stratified as low-risk (LR), intermediate-risk (IR), or high-risk (HR) based on clinical features and measurable residual disease (MRD). AAP was categorized as early- or late-onset depending on treatment phase. Older age and IR/HR status were independent risk factors for AAP. The cumulative AAP incidence was 2.2% in LR and 5.8% in IR/HR groups. Among 298 patients who developed AAP, 92 were rechallenged with asparaginase; second episodes occurred in 20.8% of LR and 33.8% of IR/HR patients, with no increase in severity. Lack of rechallenge (HR, 2.0; 95% CI, 1.1-3.6) and Day 46 MRD ≥0.01% (HR, 3.7; 95% CI, 2.1-6.8) were independently associated with inferior event-free survival (EFS). Among patients with early-onset AAP, rechallenged patients had superior 5-year EFS compared to those not rechallenged (80.1% vs. 60.2%; P = .003). Similarly, among IR/HR group, rechallenged individuals and better 5-year EFS than those not rechallenged (82.4% vs. 60.6%; P = .004). IR/HR patients with early-onset AAP who were not rechallenged had especially poor outcomes (5-year EFS, 53.3%). These findings support considering asparaginase rechallenge in IR/HR patients with early-onset AAP when alternative therapies are limited. Chinese Clinical Trial Registry: ChiCTR2000032211.