UGT1A1 genotype influences clinical outcome in patients with intermediate-risk acute myeloid leukemia treated with cytarabine-based chemotherapy.
Alleles
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Biomarkers, Tumor
Cause of Death
Cytarabine
/ administration & dosage
Female
Genotype
Glucuronosyltransferase
/ genetics
Humans
Leukemia, Myeloid, Acute
/ drug therapy
Male
Prognosis
Proportional Hazards Models
Recurrence
Remission Induction
Retrospective Studies
Treatment Outcome
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
24
09
2019
accepted:
21
02
2020
revised:
15
02
2020
pubmed:
11
3
2020
medline:
1
12
2020
entrez:
11
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32152464
doi: 10.1038/s41375-020-0784-2
pii: 10.1038/s41375-020-0784-2
doi:
Substances chimiques
Biomarkers, Tumor
0
Cytarabine
04079A1RDZ
UGT1A1 enzyme
EC 2.4.1.-
Glucuronosyltransferase
EC 2.4.1.17
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2925-2933Références
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