Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia
Publication date
2015-06-26
Authors
Den Hoed, M. A H
Lopez-Lopez, E.
Te Winkel, M. L.
Tissing, Wim J.E.
De Rooij, Johan
Gutierrez-Camino, A.
Garcia-Orad, A.
Den Boer, E.
Pieters, Rob
Pluijm, S M F
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Document Type
Article
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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
Keywords
Pharmacology, Molecular Medicine, Genetics, Journal Article, Research Support, Non-U.S. Gov't
Citation
Den Hoed, M A H, Lopez-Lopez, E, Te Winkel, M L, Tissing, W, De Rooij, J D E, Gutierrez-Camino, A, Garcia-Orad, A, Den Boer, E, Pieters, R, Pluijm, S M F, De Jonge, R & Van Den Heuvel-Eibrink, M M 2015, 'Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia', The Pharmacogenomics Journal, vol. 15, no. 3, pp. 248-254. https://doi.org/10.1038/tpj.2014.63