Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia

M. A H Den Hoed; E. Lopez-Lopez; M. L. Te Winkel; W. Tissing; J. D E De Rooij; A. Gutierrez-Camino; A. Garcia-Orad; E. Den Boer; R. Pieters; S. M F Pluijm; R. De Jonge; M. M. Van Den Heuvel-Eibrink

doi:10.1038/tpj.2014.63

Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia

M. A H Den Hoed, E. Lopez-Lopez, M. L. Te Winkel, W. Tissing, J. D E De Rooij, A. Gutierrez-Camino, A. Garcia-Orad, E. Den Boer, R. Pieters, S. M F Pluijm, R. De Jonge, M. M. Van Den Heuvel-Eibrink^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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

Original language	English
Pages (from-to)	248-254
Number of pages	7
Journal	The Pharmacogenomics Journal
Volume	15
Issue number	3
DOIs	https://doi.org/10.1038/tpj.2014.63
Publication status	Published - 26 Jun 2015

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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, 15(3), 248-254. https://doi.org/10.1038/tpj.2014.63

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title = "Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia",

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",

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Den Hoed, MAH, Lopez-Lopez, E, Te Winkel, ML, Tissing, W, De Rooij, JDE, Gutierrez-Camino, A, Garcia-Orad, A, Den Boer, E, Pieters, R, Pluijm, SMF, De Jonge, R & Van Den Heuvel-Eibrink, MM 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

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AU - Den Hoed, M. A H

AU - Lopez-Lopez, E.

AU - Te Winkel, M. L.

AU - Tissing, W.

AU - De Rooij, J. D E

AU - Gutierrez-Camino, A.

AU - Garcia-Orad, A.

AU - Den Boer, E.

AU - Pieters, R.

AU - Pluijm, S. M F

AU - De Jonge, R.

AU - Van Den Heuvel-Eibrink, M. M.

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AB - 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

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Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia

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