title: Risk Factors for Asparaginase-associated Pancreatitis: A Systematic Review.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: *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.
authors.forename: Judy-April
authors.initials: JA
authors.lastname: Oparaji
authors.forename: Fateema
authors.initials: F
authors.lastname: Rose
authors.forename: Debra
authors.initials: D
authors.lastname: Okafor
authors.forename: Amari
authors.initials: A
authors.lastname: Howard
authors.forename: Rose L
authors.initials: RL
authors.lastname: Turner
authors.forename: Abrahim I
authors.initials: AI
authors.lastname: Orabi
authors.forename: Craig
authors.initials: C
authors.lastname: Byersdorfer
authors.forename: Qi
authors.initials: Q
authors.lastname: Mi
authors.forename: Kim
authors.initials: K
authors.lastname: Ritchey
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lowe
authors.forename: Sohail Z
authors.initials: SZ
authors.lastname: Husain
mesh_terms: D000367:Age Factors; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010195:Pancreatitis / Q000139:chemically induced* / Q000209:etiology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase