Risk factors and outcome of asparaginase-associated pancreatitis in pediatric acute lymphoblastic leukemia
Seham Hassan1, Sonia Ahmed2, Nesreen Ali2
1Pediatric Oncology Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Insights
Older children and high-dose asparaginase increase the risk of asparaginase-associated pancreatitis (AAP) in acute lymphoblastic leukemia (ALL) treatment. Careful consideration is needed when re-challenging asparaginase due to pancreatitis and relapse risks.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Pharmacology
Background:
- Asparaginase-associated pancreatitis (AAP) is a serious complication in pediatric acute lymphoblastic leukemia (ALL) treatment.
- Managing AAP is challenging, with potential for severe outcomes.
Purpose of the Study:
- To determine the incidence and risk factors of AAP in pediatric ALL patients.
- To evaluate the impact of AAP on treatment outcomes, including relapse and survival.
- To assess the safety and outcomes of asparaginase re-challenge in patients who developed AAP.
Main Methods:
- Retrospective study of 1804 pediatric ALL patients treated between June 2012 and December 2017.
- Analysis of patient demographics, clinical data, treatment regimens, and AAP occurrence.
- Multivariate analysis to identify independent risk factors for AAP and assess its impact on event-free survival (EFS) and cumulative incidence of relapse (CIR).
Main Results:
- The incidence of AAP was 3.5% (63/1804 patients).
- Independent risk factors for AAP included older age (≥10 years) and high-dose asparaginase regimens.
- Severe AAP had a high mortality rate (37.5%), while mild/moderate AAP did not increase mortality.
- Asparaginase re-challenge occurred in 62% of patients, with a 30.8% recurrence rate of AAP but no associated mortality.
- Patients re-challenged with asparaginase had a lower relapse rate (23%) compared to those not re-challenged (37.5%).
- AAP was associated with lower 5-year EFS (63.5% vs. 77%) and higher CIR (24.3% vs. 14.4%), but this impact was not significant after adjusting for other factors.
Conclusions:
- Older age and high-dose asparaginase are significant risk factors for AAP in pediatric ALL.
- The decision to re-challenge with asparaginase requires balancing the risk of recurrent pancreatitis against the risk of leukemic relapse.
Background:
Asparaginase-associated pancreatitis (AAP) poses a significant challenge in pediatric patients with acute lymphoblastic leukemia (ALL), with its severity ranging from mild cases to potentially life-threatening conditions.
Aim:
To study the incidence, risk factors of AAP, and its impact on outcome in pediatric ALL patients in a large pediatric oncology hospital in a low-and middle-income country.
Patient And Methods:
This retrospective study included 1804 pediatric patients newly diagnosed with ALL at a single tertiary care center from June 2012 to December 2017. They were treated with ALL protocol adopted from St Jude total study XV including native E. coli L-asparaginase.
Results:
Sixty-three (3.5%) patients experienced AAP. Age ≥10 years at diagnosis, initial white blood cell count (WBC) ≥50x109/L, and standard/high-risk treatment regimen were significantly associated with developing AAP. By multivariate analysis, age ≥10 years and high-dose asparaginase regimens remained significant risk factors for AAP. Mild/moderate AAP was reported in 47 (75%) patients without associated mortality, however, 6/16 (37.5%) patients with severe pancreatitis died. Asparaginase was re-challenged in 39/63 (62%) patients of whom 12 patients (30.8%) experienced recurrent AAP without mortality. Patients who were not re-exposed to asparaginase had a relapse rate of 37.5% compared to 23% for those who were re-challenged. The 5-year event-free-survival (EFS) and cumulative incidence of relapse (CIR) were 63.5% and 24.3%; respectively; for patients with AAP compared to 77% and 14.4% for those without AAP (P=0.01, P=0.02; respectively). However, AAP lost its significant impact when adjusted to other factors including age, WBC, immunophenotype, and ALL risk stratification (EFS: HR1.32; 95%CI, 0.88-1.98; P=0.17 and CIR: HR1.44; 95%CI, 0.86-2.4; P=0.16).
Conclusion:
Older age and high-dose asparaginase regimens are independent risk factors of AAP. The decision to re-challenge asparaginase should be carefully considered balancing the risk of recurrent pancreatitis against the potential risk of leukemic relapse.
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