Pharmacogenetic aspects of efficacy and safety of methotrexate treatment in pediatric acute lymphoblastic leukemia.
Drug Metab Pers Ther
; 38(4): 349-357, 2023 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-38098143
ABSTRACT
OBJECTIVES:
To evaluate the role of ABCB1 (C3435T rs1045642, rs1128503, rs2032582, rs4148738), SLCO1B1 T521C rs4149056 genetic polymorphisms in the development of major types of methotrexate (MTX) toxicities and the occurrence of a terminal event (death, relapse) in pediatric ÐLL.METHODS:
The study included 124 patients diagnosed with pediatric ALL. All patients treated according to the protocols of the German BFM group (2002/2009) with high-dose (1,000, 2,000 and 5,000â¯mg/m2) methotrexate. MTX-related toxicities, including hematologic, hepatic and renal, were evaluated according to the common terminology criteria for adverse events version 5.0 (CTCAE v.5.0). Real-time PCR method was used to investigate polymorphisms of ABCB1 and SLCO1B1 genes. The study material was peripheral blood.RESULTS:
A competitive analysis demonstrated significant relationships between MTX ADRs. The results of the study support the existence of relationships between some ADRs and MTX kinetics. An associative analysis showed association with the development of AEs to methotrexate indicating their clinical significance from different genetic polymorphisms protein-transporters. The available results confirm the associations of the studied genes with the increased risk of high doses MTX toxic ADRs and terminal events.CONCLUSIONS:
Complementing the existing criteria for pediatric ALL risk groups with pharmacogenetic indicators will allow further individualization of therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metotrexato
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
Limite:
Child
/
Humans
Idioma:
En
Revista:
Drug Metab Pers Ther
Ano de publicação:
2023
Tipo de documento:
Article