Asparaginase-associated pancreatitis: a study on phenotype and genotype in the NOPHO ALL2008 protocol

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Asparaginase (ASP)-associated pancreatitis (AAP) occurs during acute lymphoblastic leukemia treatment. Among 1285 children (1.0-17.9 years) diagnosed during July 2008-December 2014 and treated according to the Nordic/Baltic ALL2008 protocol, 86 (cumulative incidence = 6.8%) developed AAP. Seventy-three cases were severe (diagnostic AAP criteria persisting 472 h) and 13 mild. Cases were older than controls (median: 6.5 vs 4.5 years; P = 0.001). Pseudocysts developed in 28%. Of the 20 re-exposed to ASP, 9 (45%) developed a second AAP. After a median follow-up of 2.3 years, 8% needed permanent insulin therapy, and 7% had recurrent abdominal pain. Germline DNA on 62 cases and 638 controls was genotyped on Omni2.5exome-8-v1.2 BeadChip arrays. Overall, the ULK2 variant rs281366 showed the strongest association with AAP (P = 5.8x10(-7); odds ratio (OR) = 6.7). Cases with the rs281366 variant were younger (4.3 vs 8 years; P = 0.015) and had lower risk of AAP-related complications (15% vs 43%; P = 0.13) compared with cases without this variant. Among 45 cases and 517 controls
Original languageEnglish
JournalLeukemia
Volume31
Issue number2
Pages (from-to)325-332
ISSN0887-6924
DOIs
Publication statusPublished - 2016
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