Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia.
Pharmacogenomics J
; 15(3): 248-54, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25348617
ABSTRACT
Methotrexate (MTX) is an effective and toxic chemotherapeutic drug in the treatment of pediatric acute lymphoblastic leukemia(ALL). In this prospective study, we aimed to identify metabolic and genetic determinants of MTX toxicity. One hundred and thirty-four Dutch pediatric ALL patients were treated with four high infusions MTX (HD-MTX 5 g m(-2)) every other week according to the DCOG-ALL-10 protocol. Mucositis (National Cancer Institute grade ⩾ 3) was the most frequent occurring toxicity during the HD-MTX phase (20%) and occurred especially after the first MTX course. Mucositis was not associated with plasma MTX, plasma folate or plasma homocysteine levels. Patients with mucositis had higher erythrocyte folate levels at the start of protocol M than patients without mucositis (median 1.4 vs 1.2 µmol l(-1), P<0.008), this could reflect an increased MTX uptake in mucosal cells of patients with mucositis. From 17 single-nucleotide polymorphisms in the MTX pathway, only patients with the wild-type variant of rs7317112 SNP in the ABCC4 gene had more mucositis (AA (39%) vs AG/GG (15%), P=0.016). We found no evidence that erythrocyte folate levels mediate in the association between the rs7317112 and mucositis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metotrexato
/
Polimorfismo de Nucleotídeo Único
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Mucosite
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Antimetabólitos Antineoplásicos
Tipo de estudo:
Guideline
/
Observational_studies
/
Risk_factors_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
/
Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article