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Risk Factors for Asparaginase-associated Pancreatitis: A Systematic Review
Judy-April Oparaji1, Fateema Rose, Debra Okafor
1*Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, MD †Department of Pediatrics ‡Health Sciences Library System §Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA.
Insights
Older age, pegylated asparaginase, and high-risk acute lymphoblastic leukemia (ALL) categories may increase the risk of asparaginase-associated pancreatitis (AAP). Further research is needed to understand AAP development in ALL patients.
Area of Science:
- Oncology
- Gastroenterology
- Pediatric Hematology/Oncology
Background:
- Asparaginase is a critical treatment for childhood acute lymphoblastic leukemia (ALL).
- Asparaginase-associated pancreatitis (AAP) is a significant complication, often leading to treatment cessation and poorer outcomes.
- Predicting AAP risk is challenging due to unclear risk factors.
Purpose of the Study:
- To systematically review and identify potential risk factors for asparaginase-associated pancreatitis (AAP).
Main Methods:
- A systematic literature review was conducted from January 1946 to May 2015.
- 1842 citations were screened, resulting in a review of 59 full articles.
- 10 articles met the inclusion criteria for the final analysis.
Main Results:
- Two studies indicated children over 10 years old had a >2-fold risk of AAP.
- Higher incidence of pancreatitis was observed in patients with high-risk ALL categories (2 studies).
- Pegylated asparaginase use was associated with a higher AAP incidence in one study.
Conclusions:
- Older age, asparaginase formulation, and higher ALL risk stratification appear to have a limited role in AAP development.
- Higher asparaginase dosing may also play a minor role.
- Further investigation into the mechanisms of AAP is required.
Goals:
To evaluate potential risk factors for the development of asparaginase-associated pancreatitis (AAP), we performed a systematic review of the current literature from January 1946 through May 2015.
Background:
Asparaginase, a primary treatment for the most common childhood cancer, acute lymphoblastic leukemia (ALL), is a well-described cause of pancreatitis. Further, pancreatitis is among the most burdensome and common complications of asparaginase treatment and represents a major reason for early-drug termination and inferior outcomes. The literature lacks clarity about the risk factors for AAP, and this knowledge gap has hampered the ability to reliably predict which patients are likely to develop AAP.
Study:
In an expansive screen, 1842 citations were funneled into a review of 59 full articles, of which 10 were deemed eligible based on predetermined inclusion criteria.
Results:
Of the 10 identified studies, only 2 studies showed that children above 10 years of age had a >2-fold risk of AAP compared with younger children. Patients placed in high-risk ALL categories had a greater incidence of pancreatitis in 2 studies. In addition, use of pegylated asparaginase resulted in a higher incidence of AAP in 1 study.
Conclusions:
In this systematic review, older age, asparaginase formulation, higher ALL risk stratification, and higher asparaginase dosing appear to play a limited role in the development of AAP. Further studies are needed to probe the underlying mechanisms contributing to the development of pancreatitis in patients receiving asparaginase.