TY  - JOUR
AU  - Junk, Stefanie V
AU  - Schaeffeler, Elke
AU  - Zimmermann, Martin
AU  - Möricke, Anja
AU  - Beier, Rita
AU  - Schütte, Peter
AU  - Fedders, Birthe
AU  - Alten, Julia
AU  - Hinze, Laura
AU  - Klein, Norman
AU  - Kulozik, Andreas
AU  - Muckenthaler, Martina U
AU  - Koehler, Rolf
AU  - Borkhardt, Arndt
AU  - Vijayakrishnan, Jayaram
AU  - Ellinghaus, David
AU  - Forster, Michael
AU  - Franke, Andre
AU  - Wintering, Astrid
AU  - Kratz, Christian P
AU  - Schrappe, Martin
AU  - Schwab, Matthias
AU  - Houlston, Richard S
AU  - Cario, Gunnar
AU  - Stanulla, Martin
TI  - Chemotherapy-related hyperbilirubinemia in pediatric acute lymphoblastic leukemia: a genome-wide association study from the AIEOP-BFM ALL study group.
JO  - Journal of experimental & clinical cancer research
VL  - 42
IS  - 1
SN  - 0392-9078
CY  - London
PB  - BioMed Central
M1  - DKFZ-2023-00096
SP  - 21
PY  - 2023
AB  - Characterization of clinical phenotypes in context with tumor and host genomic information can aid in the development of more effective and less toxic risk-adapted and targeted treatment strategies. To analyze the impact of therapy-related hyperbilirubinemia on treatment outcome and to identify contributing genetic risk factors of this well-recognized adverse effect we evaluated serum bilirubin levels in 1547 pediatric patients with acute lymphoblastic leukemia (ALL) and conducted a genome-wide association study (GWAS).Patients were treated in multicenter trial AIEOP-BFM ALL 2000 for pediatric ALL. Bilirubin toxicity was graded 0 to 4 according to the Common Toxicity Criteria (CTC) of the National Cancer Institute. In the GWAS discovery cohort, including 650 of the 1547 individuals, genotype frequencies of 745,895 single nucleotide variants were compared between 435 patients with hyperbilirubinemia (CTC grades 1-4) during induction/consolidation treatment and 215 patients without it (grade 0). Replication analyses included 224 patients from the same trial.Compared to patients with no (grade 0) or moderate hyperbilirubinemia (grades 1-2) during induction/consolidation, patients with grades 3-4 had a poorer 5-year event free survival (76.6 ± 3
KW  - Childhood acute lymphoblastic leukemia (Other)
KW  - Hepatotoxicity (Other)
KW  - Hyperbilirubinemia (Other)
KW  - Treatment-related toxicity (Other)
KW  - UGT1A (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36639636
C2  - pmc:PMC9838013
DO  - DOI:10.1186/s13046-022-02585-x
UR  - https://inrepo02.dkfz.de/record/186752
ER  -