Additional file 1 of Chemotherapy-related hyperbilirubinemia in pediatric acute lymphoblastic leukemia: a genome-wide association study from the AIEOP-BFM ALL study group
Creators: name: Junk, Stefanie V.
name: Schaeffeler, Elke
name: Zimmermann, Martin
name: Möricke, Anja
name: Beier, Rita
name: Schütte, Peter
name: Fedders, Birthe
name: Alten, Julia
name: Hinze, Laura
name: Klein, Norman
name: Kulozik, Andreas
name: Muckenthaler, Martina U.
name: Koehler, Rolf
name: Borkhardt, Arndt
name: Vijayakrishnan, Jayaram
name: Ellinghaus, David
name: Forster, Michael
name: Franke, Andre
name: Wintering, Astrid
name: Kratz, Christian P.
name: Schrappe, Martin
name: Schwab, Matthias
name: Houlston, Richard S.
name: Cario, Gunnar
name: Stanulla, Martin
Publisher: name: figshare
Year: 2023
Subjects: subject: Genetics
subject: FOS: Biological sciences

description: Additional file 1: Suppl. Table 1. Treatment details of protocol AIEOP-BFM ALL 2000. Suppl. Table 2. Clinical characteristics of the patients in the study cohort by severity of bilirubin toxicity during induction/consolidation (protocols IA/IB, n = 1547). Suppl. Table 3. Characteristics of the patients in the GWAS discovery cohort by serum bilirubin levels during induction/consolidation (n = 650). Suppl. Table 4. Characteristics of the patients in the GWAS discovery cohort compared to all patients of the study cohort with toxicity information. Suppl. Table 5. Summary of genome-wide association analysis for therapy-related hyperbilirubinemia during induction/consolidation (protocols IA/IB). Suppl. Table 6. Allelic association of hyperbilirubinemia phenotype with the 20 most strongly associated variants around rs6744284 resulting from genotype imputation. Suppl. Table 7. Genotypic association between hyperbilirubinemia phenotype and the 20 most strongly associated SNV around rs6744284 after genotype imputation. Suppl. Table 8. Adjusted genotypic association of rs6744284 with hyperbilirubinemia during protocols IA/IB and later therapeutic elements, including age and immunophenotype as covariates. Suppl. Table 9. Genotypic association of rs6744284 with hyperbilirubinemia phenotype stratified for potential effect modifiers. Suppl. Table 10. Characteristics of acute lymphoblastic leukemia (ALL) patients included in the replication cohort (n = 224). Suppl. Table 11. Characteristics of acute lymphoblastic leukemia (ALL) patients included in subsequent UGT1A1*28/*37 genotyping (n = 544). Suppl. Table 12. Association of identified risk loci and known Gilbert’s syndrome related variants with hyperbilirubinemia. Suppl. Table 13. Correlation of rs6744284 with imputed top SNV and UGT1A variations related to hyperbilirubinemia and the Gilbert’s syndrome. Suppl. information on the correlation analysis of known Gilbert’s syndrome (GS) related variations with rs6744284. Suppl. information on the impact of hyperbilirubinemia on therapy delays in the discovery cohort. Suppl. Table 14. Clinical characteristics of the acute lymphoblastic leukemia (ALL) patients of the discovery cohort according to the severity of bilirubin toxicity during induction/consolidation (protocols IA/IB, n = 650). Suppl. Table 15. Estimated hazard ratios from the multivariable Cox proportional model on the hazard of relapse in patients with high hyperbilirubinemia (≥CTC grade 3) during induction and/or consolidation (n = 68). Suppl. Fig. 1. Consolidated Standards of Reporting Trials (CONSORT) diagram of inclusion criteria for the study population (N = 1547). Suppl. Fig. 2. Estimated 5-year event-free survival (EFS) and cumulative incidence of relapse (CIR) at 5 years in the study cohort by the maximum transaminase levels during protocol IA/IB [%]. Suppl. Fig. 3. Regional plot of association results and recombination rates for the identified risk locus in the UGT1A region (2q37). Suppl. Fig. 4. Total serum bilirubin levels by treatment element and rs6744284 genotype. Suppl. Fig. 5. Estimated 5-year event-free survival (EFS) and cumulative incidence of relapse (CIR) at 5 years in the discovery cohort by the maximum transaminase levels during protocol IA/IB [%].