{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:59:19Z","timestamp":1790787559925,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patient and methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty-three (3.5%) patients experienced AAP. Age \u226510 years at diagnosis, initial white blood cell count (WBC) \u226550x10<jats:sup>9<\/jats:sup>\/L, and standard\/high-risk treatment regimen were significantly associated with developing AAP. By multivariate analysis, age \u226510 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; <jats:italic>P=0<\/jats:italic>.16).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1606261","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T05:28:34Z","timestamp":1750915714000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Risk factors and outcome of asparaginase-associated pancreatitis in pediatric acute lymphoblastic leukemia"],"prefix":"10.3389","volume":"15","author":[{"given":"Seham","family":"Hassan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesreen","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer","family":"Mokhles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman","family":"Zaky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Reda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah H.","family":"Youssef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Hammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omneya","family":"Hassanain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman","family":"Sidhom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.902117","article-title":"Current use of asparaginase in acute lymphoblastic leukemia\/lymphoblastic lymphoma","volume":"10","author":"Maese","year":"2022","journal-title":"Front Pediatr"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30424-2","article-title":"Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukemia: an observational Ponte di Legno Toxicity Working Group study","volume":"18","author":"Wolthers","year":"2017","journal-title":"Lancet Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2006.07.009","article-title":"Pharmacological and clinical evaluation of L-asparaginase in the treatment of leukemia","volume":"61","author":"Narta","year":"2007","journal-title":"Crit Rev Oncol Hematol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v99.8.2734","article-title":"Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid Malignancies: results of a randomized European Organization for Research and Treatment of Cancer-Children\u2019s Leukemia Group phase 3 trial","volume":"99","author":"Duval","year":"2002","journal-title":"Blood>"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-200203000-00004","article-title":"A pharmacoeconomic analysis of pegaspargase versus native Escherichia coli L-asparaginase for the treatment of children with standard-risk, acute lymphoblastic leukemia: the Children\u2019s Cancer Group study (CCG-1962)","volume":"24","author":"Kurre","year":"2002","journal-title":"J Pediatr Hematol Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03692","article-title":"Efficacy and toxicity of pegaspargase and calaspargase pegol in childhood acute lymphoblastic leukemia: results of DFCI 11-001","volume":"39","author":"Vrooman","year":"2021","journal-title":"J Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0285948","article-title":"Quality comparison of a state-of-the-art preparation of a recombinant L-asparaginase derived from Escherichia coli with an alternative asparaginase product","volume":"18","author":"Schnuchel","year":"2023","journal-title":"PloS One"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30035-3","article-title":"Ponte di Legno toxicity working group. 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