Genetic factors involved in delayed methotrexate elimination in children with acute lymphoblastic leukemia.
Pediatr Blood Cancer
; 68(5): e28858, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33501733
ABSTRACT
BACKGROUND:
Delayed excretion of methotrexate can lead to life-threatening toxicity that may result in treatment cessation, irreversible organ damage, and death. Various factors have been demonstrated to influence the pharmacokinetic process of methotrexate, including genetic and nongenetic factors.METHODS:
We investigated the genetic factors primarily related to the metabolic pathway of methotrexate in children with acute lymphoblastic leukemia with delayed elimination, defined as C44-48h ≥ 1.0µmol/L in this study. A total of 196 patients (delayed excretion group 98; normal excretion group 98) who received CCCG-ALL-2015 protocol after propensity score-matched analysis were included in the study. Twenty-eight target single-nucleotide polymorphisms (SNPs) were analyzed by multiplex polymerase chain reaction and sequencing, and 25 SNPs were finally included in the study.RESULTS:
The genotype distribution of SLCO1B1 rs2306283 SNP was different between the delayed and normal excretion groups. SLCO1B1 rs2306283 AA carriers had a significantly lower methotrexate C44-48h /D ratio than GG carriers in both groups. Furthermore, compared with the normal excretion group, SLCO1B1 rs2306283 AG and GG were risk factors for developing oral mucositis (odds ratio [OR] 2.13; 95% confidence interval [CI] 1.11-4.08; P < .001), hepatotoxicity (OR 2.12; 95% CI 1.26-3.56; P < .001), and myelosuppression (OR 1.21; 95% CI 1.04-1.41; P = .005) in delayed excretion group.CONCLUSIONS:
The results from this study indicate the potential role of SLCO1B1 rs2306283 as a pharmacogenomic marker to guide and optimize methotrexate treatment for delayed elimination in children with acute lymphoblastic leukemia.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metotrexato
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Transportador 1 de Ânion Orgânico Específico do Fígado
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Variantes Farmacogenômicos
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Antimetabólitos Antineoplásicos
Tipo de estudo:
Guideline
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Observational_studies
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Risk_factors_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Pediatr Blood Cancer
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China