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

B. O. Wolthers, Thomas L. Frandsen, Jonas Abrahamsson, B. K. Albertsen, L. R. Helt, Mats Heyman, Olafur G. Jonsson, L. T. Korgvee, B. Lund, R. A. Raja, K. K. Rasmussen, M. Taskinen, M. Tulstrup, G. E. Vaitkeviciene, Rachita Yadav, R. Gupta, K. Schmiegelow

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    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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