Asparaginase-Associated Pancreatitis in ALL: Results from the NOPHO ALL2008 Treatment of Patients 1-45 Years

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.3820-3820
• Main Authors: Rank, Cecilie Utke, Wolthers, Benjamin Ole, Grell, Kathrine, Albertsen, Birgitte Klug, Frandsen, Thomas Leth, Overgaard, Ulrik Malthe, Toft, Nina, Nielsen, Ove Juul, Wehner, Peder Skov, Harila-Saari, Arja, Heyman, Mats, Abrahamsson, Jonas, Norén-Nyström, Ulrika, Tomaszewska-Toporska, Beata, Lund, Bendik, Jarvis, Kirsten Brunsvig, Quist-Paulsen, Petter, Vaitkeviciene, Goda Elizabeta, Griškevičius, Laimonas, Taskinen, Mervi, Wartiovaara-Kautto, Ulla, Lepik, Kristi, Punab, Mari, Jónsson, Ólafur Gísli, Schmiegelow, Kjeld
• Format: Article
• Language: English
• Subjects: 2019; 61st ASH Annual Meeting. December 7-10; Cancer and Oncology; Cancer och onkologi; Orlando; Pediatrics; Pediatrik; USA
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2019-122275

Premature discontinuation of asparaginase reduces cure rate in contemporary acute lymphoblastic leukemia (ALL) treatment. One of the commonest causes of asparaginase truncation is asparaginase-associated pancreatitis (AAP). We prospectively registered AAP during treatment of 2,448 consecutive Nordic/Baltic ALL patients aged 1.0-45.9 years treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol (7/2008-10/2018). The Day 280 cumulative incidence of first-time AAP (including 99% (167/168) of AAP events at this time point) was 8.3% (95% confidence interval (CI) 7.0-9.9) with a median time of 104 days (interquartile range (IQR) 70-145) from ALL diagnosis to AAP, with a median of 10 days (IQR 6-13) from last asparaginase exposure, and after a median number of five asparaginase doses (IQR 3-7, max 14 doses). All patients received polyethylene glycol conjugated Escherichia coli-derived asparaginase as standard treatment. Eighty-five percent (140/164, unknown in N=4) of AAP events were severe (AAP-associated symptoms and/or pancreatic enzymes >3x upper normal limit lasting >72 hours or with hemorrhagic pancreatitis, pancreatic abscess, or pseudocyst). Four age groups were defined: 1.0-4.9, 5.0-8.9, 9.0-16.9, and 17.0-45.9 years-each containing approximately 25% of the AAP events. Compared with patients aged 1.0-4.9 years, adjusted (sex, immunophenotype, and white blood cell count) hazard ratios (HR) of AAP were associated with higher age (5.0-8.9 years: HR 2.3, 95% CI 1.5-3.6, P