Risk of Asparaginase-Associated Pancreatitis in Patients With Acute Lymphoblastic Leukemia

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In a study reported in the Journal of Clinical Oncology, Rank et al found a similar risk of asparaginase-associated pancreatitis in older children, adolescents, and adults and greater associated morbidity in adolescents with acute lymphoblastic leukemia treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol.

Study Details

The study included 2,448 patients aged 1.0 to 45.9 years diagnosed between July 2008 and October 2018 who were treated according to the NOPHO ALL2008 protocol in Denmark, Estonia, Finland, Iceland, Lithuania, Norway, and Sweden. Asparaginase-associated pancreatitis was identified in 168 patients.

Asparaginase-Associated Pancreatitis Risk and Complications

The 280-day cumulative incidence of asparaginase-associated pancreatitis was 7.0% for children (aged 1.0–9.9 years; including 5.4% in those aged 1.0–4.9 years and 10.2% in those aged 5.0–8.9 years), 10.1% for adolescents (aged 10.0–17.9 years), and 11.0% for adults (aged 18.0–45.9 years; overall P = .03). On multivariate analysis, compared with children aged 1.0–9.9 years, adjusted hazard ratios for asparaginase-associated pancreatitis were 1.6 (P = .02) for adolescents and 1.6 (P = .02) for adults (aged 18.0–45.9 years).


  • Older children, adolescents, and adults had a similar risk for asparaginase-associated pancreatitis.
  • Adolescents were at increased risk of acute and persisting complications.

Compared with children, adolescents were at increased risk of both acute (odds ratio [OR] = 5.2, P = .0005) and persisting asparaginase-associated pancreatitis complications (OR = 6.7, P = .0002). Adults were at increased risk of persisting complications (OR = 4.1, P = .01).

Among 34 patients undergoing asparaginase rechallenge, 15 developed a second associated pancreatitis episode. Treatment was truncated in 17 of 21 patients with asparaginase-associated pancreatitis who had subsequent relapse of leukemia, with increased risk of relapse not being associated with either asparaginase-associated pancreatitis or asparaginase truncation.

The investigators concluded, “Older children and adults had similar asparaginase-associated pancreatitis risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.”

Kjeld Schmiegelow, MD, DrMedSci, of the Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the Research Foundation of Rigshospitalet, Krista and Viggo Petersen’s Foundation, Danish Childhood Cancer Foundation, and Danish Cancer Society. For full disclosures of the study authors, visit

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