Asparaginase-Associated Pancreatitis in Pediatric Patients with Acute Lymphoblastic Leukemia: Current Perspectives.

Asparaginase therapy is a vital agent in the treatment of acute lymphoblastic leukemia (ALL), with increasing evidence of its high importance in high-risk ALL populations. However, despite the clear clinical and biological benefits of asparaginase therapy, many patients experience toxicities. A well-known treatment-limiting toxicity is asparaginase-associated pancreatitis (AAP). If severe, it necessitates discontinuation of asparaginase therapy, which can lead to a higher risk of relapse in patients with ALL. New protocols for ALL therapy have increased overall total doses of asparaginase therapy in select high-risk populations and have incorporated longer half-life formulations of pegylated asparaginase. Treatment drug monitoring has also allowed assurance of adequate levels of asparagine depletion throughout treatment. It is currently unknown if these changes will increase rates of AAP. Interestingly, important pharmacogenomics data, such as single nucleotide polymorphisms, can identify patients at the highest risk for severe AAP. The incidence of AAP in recent trials, current pharmacogenomic data that could further our understanding of the disease, and the importance of cautiously re-exposing patients to further asparaginase treatment after an initial episode of AAP are discussed.