trypsinogen and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Asparaginase-associated pancreatitis is a life-threatening toxicity to childhood acute lymphoblastic leukemia treatment. To elucidate genetic predisposition and asparaginase-associated pancreatitis pathogenesis, ten trial groups contributed remission samples from patients aged 1.0-17.9 years treated for acute lymphoblastic leukemia between 2000 and 2016. Cases (n=244) were defined by the presence of at least two of the following criteria: (i) abdominal pain; (ii) levels of pancreatic enzymes ≥3 × upper normal limit; and (iii) imaging compatible with pancreatitis. Controls (n=1320) completed intended asparaginase therapy, with 78% receiving ≥8 injections of pegylated-asparaginase, without developing asparaginase-associated pancreatitis. rs62228256 on 20q13.2 showed the strongest association with the development of asparaginase-associated pancreatitis (odds ratio=3.75;

Topics: Adolescent; Alleles; Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Infant; Male; Models, Biological; Pancreatitis; Phenotype; Polyethylene Glycols; Polymorphism, Single Nucleotide; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trypsin; Trypsinogen