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

Asparaginase-associated pancreatitis (AAP) is a significant complication in pediatric 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 7640 patients (aged 1 month to 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 and day 46 MRD of ≥0.01% were independently associated with inferior event-free survival (EFS). Among patients with early-onset AAP, those who were rechallenged had superior 5-year EFS than those who were not rechallenged (80.1% vs 60.2%; P = .003). Similarly, among IR/HR group, those who were rechallenged had better 5-year EFS than those who were 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. This trial was registered at www.chictr.org.cn as #ChiCTR2000032211.