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

被引:7
|
作者
Diaz-Santa, Johana [1 ]
Rodriguez-Romanos, Rocio [1 ]
Osca, Gemma [1 ]
Pratcorona, Marta [2 ]
Garrido, Ana [2 ]
Coll, Rosa [1 ]
Moret, Carla [1 ]
Escoda, Lourdes [3 ]
Tormo, Mar [4 ]
Heras, Inma [5 ]
Arnan, Montse [6 ]
Vives, Susanna [7 ]
Salamero, Olga [8 ]
Lloveras, Natalia [1 ]
Bargay, Joan [9 ]
Sampol, Antonia [10 ]
Cruz, David [1 ]
Garcia, Antoni [11 ]
Quinones, Teresa [1 ]
Esteve, Jordi [12 ]
Sierra, Jorge [2 ]
Gallardo, David [1 ]
机构
[1] Univ Girona, Hematol Dept, Catalan Inst Oncol ICO, Inst Invest Biomed Girona IDIBGI, Girona, Spain
[2] Univ Autonoma Barcelona, Hosp Santa Creu i St Pau, Inst Invest Biomed St Pau, Hematol Dept, Barcelona, Spain
[3] Hosp Joan 23, Hematol Dept, Catalan Inst Oncol ICO, Tarragona, Spain
[4] Hosp Clin, Hematol Dept, Valencia, Spain
[5] Univ Hosp Morales Meseguer, Dept Hematol, Murcia, Spain
[6] Catalan Inst Oncol ICO, Dept Hematol, Barcelona, Spain
[7] Josep Carreras Leukemia Res Inst IJC, Hematol Dept, Catalan Inst Oncol ICO, Barcelona, Spain
[8] Hosp Vall dHebro, Hematol Dept, Barcelona, Spain
[9] Hosp Son Llatzer, Hematol Dept, Palma De Mallorca, Spain
[10] Hosp Son Espases, Hematol Dept, Palma De Mallorca, Spain
[11] Hosp Arnau Vilanova, Hematol Dept, Lleida, Spain
[12] Univ Barcelona, Hematol Dept, Inst Invest Biomed August Pi i Sunyer IDIBAP, Hosp Clin, Barcelona, Spain
关键词
ACUTE MYELOGENOUS LEUKEMIA; POLYMORPHISMS; MUTATIONS; CANCER; ADULTS; IMPACT; GENE; 1A1;
D O I
10.1038/s41375-020-0784-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2925 / 2933
页数:9
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