Risk Factors for Asparaginase-associated Pancreatitis: A Systematic Review

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 earlydrug 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.