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UGT1A1 genotype influences clinical outcome in patients with intermediate-risk acute myeloid leukemia treated with cytarabine-based chemotherapy.

Authors
  • Díaz-Santa, Johana1
  • Rodríguez-Romanos, Rocío1
  • Osca, Gemma1
  • Pratcorona, Marta2
  • Garrido, Ana2
  • Coll, Rosa1
  • Moret, Carla1
  • Escoda, Lourdes3
  • Tormo, Mar4
  • Heras, Inma5
  • Arnan, Montse6
  • Vives, Susanna7
  • Salamero, Olga8
  • Lloveras, Natàlia1
  • Bargay, Joan9
  • Sampol, Antònia10
  • Cruz, David1
  • Garcia, Antoni11
  • Quiñones, Teresa1
  • Esteve, Jordi12
  • And 2 more
  • 1 Hematology Department, Catalan Institute of Oncology (ICO), Girona. Institut d'Investigació Biomèdica de Girona (IDIBGI), Universitat de Girona, Girona, Spain. , (Spain)
  • 2 Hematology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. , (Spain)
  • 3 Hematology Department, Catalan Institute of Oncology (ICO), Hospital Joan XXIII, Tarragona, Spain. , (Spain)
  • 4 Hematology Department, Hospital Clínico, Valencia, Spain. , (Spain)
  • 5 Department of Hematology, University Hospital Morales Meseguer, Murcia, Spain. , (Spain)
  • 6 Department of Hematology, Catalan Institute of Oncology (ICO), L'Hospitalet, Barcelona, Spain. , (Spain)
  • 7 Hematology Department, Catalan Institute of Oncology (ICO), Badalona, Josep Carreras Leukemia Research Institute (IJC), Badalona, Barcelona, Spain. , (Spain)
  • 8 Hematology Department, Hospital Vall d'Hebró, Barcelona, Spain. , (Spain)
  • 9 Hematology Department, Hospital de Son Llàtzer, Palma de Mallorca, Spain. , (Spain)
  • 10 Hematology Department, Hospital Son Espases, Palma de Mallorca, Spain. , (Spain)
  • 11 Hematology Department, Hospital Arnau de Vilanova, Lleida, Spain. , (Spain)
  • 12 Hematology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. , (Spain)
  • 13 Hematology Department, Catalan Institute of Oncology (ICO), Girona. Institut d'Investigació Biomèdica de Girona (IDIBGI), Universitat de Girona, Girona, Spain. [email protected] , (Spain)
Type
Published Article
Journal
Leukemia
Publisher
Springer Nature
Publication Date
Nov 01, 2020
Volume
34
Issue
11
Pages
2925–2933
Identifiers
DOI: 10.1038/s41375-020-0784-2
PMID: 32152464
Source
Medline
Language
English
License
Unknown

Abstract

The treatment of acute myeloid leukemia (AML) is adjusted according to cytogenetic risk factors and molecular markers. Cytarabine remains the main drug to treat AML, and several studies have explored the prognostic relevance of the genotype of cytarabine metabolizing enzymes in AML. Glucuronidation has been identified to be relevant in the cytarabine clearance, but there are still few data concerning the clinical impact of genetic polymorphisms known to condition the activity of UDP-glucuronosyl transferases in AML patients. Here we report the association between the UGT1A1 rs8175347 genotype and the clinical outcome of 455 intermediate-risk cytogenetic AML patients receiving cytarabine-based chemotherapy. Patients with the UGT1A1*28 homozygous variant (associated to a lower UGT1A1 activity) had a lower overall survival (OS) (25.8% vs. 45.5%; p: 0.004). Multivariate analysis confirmed this association (p: 0.008; HR: 1.79; 95% CI: 1.16-2.76). Subgroup analysis showed the negative effect of the UGT1A1*28 homozygous genotype on OS in women (14.8% vs. 52.7%; p: 0.001) but not in men. This lower OS was associated with longer neutropenia after consolidation chemotherapy and with higher mortality without previous relapse, suggesting an association between a low glucuronidation activity and mortal toxic events.

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