Asparaginase-associated pancreatitis: a study on phenotype and genotype in the NOPHO ALL2008 protocol.
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AuthorsWolthers, B O
Frandsen, T L
Albertsen, B K
Helt, L R
Jónsson, Ó G
Kõrgvee, L T
Raja, R A
Rasmussen, K K
Vaitkevičienė, G E
MetadataShow full item record
CitationAsparaginase-associated pancreatitis: a study on phenotype and genotype in the NOPHO ALL2008 protocol. 2017, 31 (2):325-332 Leukemia
AbstractAsparaginase (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 >72 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=5.8 × 10(-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 <10 years, the strongest associations with AAP were found for RGS6 variant rs17179470 (P=9.8 × 10(-9); OR=7.3). Rs281366 is located in the ULK2 gene involved in autophagy, and RGS6 regulates G-protein signaling regulating cell dynamics. More than 50% of AAP cases <10 years carried one or both risk alleles.
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- Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol.
- Authors: Raja RA, Schmiegelow K, Albertsen BK, Prunsild K, Zeller B, Vaitkeviciene G, Abrahamsson J, Heyman M, Taskinen M, Harila-Saari A, Kanerva J, Frandsen TL, Nordic Society of Paediatric Haematology and Oncology (NOPHO) group.
- Issue date: 2014 Apr
- Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia: Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age.
- Authors: Rank CU, Wolthers BO, Grell K, Albertsen BK, Frandsen TL, Overgaard UM, Toft N, Nielsen OJ, Wehner PS, Harila-Saari A, Heyman MM, Malmros J, Abrahamsson J, Norén-Nyström U, Tomaszewska-Toporska B, Lund B, Jarvis KB, Quist-Paulsen P, Vaitkevičienė GE, Griškevičius L, Taskinen M, Wartiovaara-Kautto U, Lepik K, Punab M, Jónsson ÓG, Schmiegelow K
- Issue date: 2020 Jan 10
- Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia: an observational Ponte di Legno Toxicity Working Group study.
- Authors: Wolthers BO, Frandsen TL, Baruchel A, Attarbaschi A, Barzilai S, Colombini A, Escherich G, Grell K, Inaba H, Kovacs G, Liang DC, Mateos M, Mondelaers V, Möricke A, Ociepa T, Samarasinghe S, Silverman LB, van der Sluis IM, Stanulla M, Vrooman LM, Yano M, Zapotocka E, Schmiegelow K, Ponte di Legno Toxicity Working Group.
- Issue date: 2017 Sep
- Trypsin-encoding <i>PRSS1-PRSS2</i> variations influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report.
- Authors: Wolthers BO, Frandsen TL, Patel CJ, Abaji R, Attarbaschi A, Barzilai S, Colombini A, Escherich G, Grosjean M, Krajinovic M, Larsen E, Liang DC, Möricke A, Rasmussen KK, Samarasinghe S, Silverman LB, van der Sluis IM, Stanulla M, Tulstrup M, Yadav R, Yang W, Zapotocka E, Gupta R, Schmiegelow K, Ponte di Legno toxicity working group.
- Issue date: 2019 Mar
- Asparaginase-associated pancreatitis is not predicted by hypertriglyceridemia or pancreatic enzyme levels in children with acute lymphoblastic leukemia.
- Authors: Raja RA, Schmiegelow K, Sørensen DN, Frandsen TL
- Issue date: 2017 Jan