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PLoS One. 2014 Jan 3;9(1):e82681. doi: 10.1371/journal.pone.0082681. eCollection 2014.

Association of ABCC2 -24C>T polymorphism with high-dose methotrexate plasma concentrations and toxicities in childhood acute lymphoblastic leukemia.

Author information

1
Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
2
Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
3
Department of Pediatric Hematology/Oncology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Erratum in

  • PLoS One. 2014;9(3):e91384.

Abstract

Methotrexate (MTX) is a key agent for the treatment of childhood acute lymphoblastic leukemia (ALL). Increased MTX plasma concentrations are associated with a higher risk of adverse drug effects. ATP-binding cassette subfamily C member 2 (ABCC2) is important for excretion of MTX and its toxic metabolite. The ABCC2 -24C>T polymorphism (rs717620) reportedly contributes to variability of MTX kinetics. In the present study, we assessed the association between the ABCC2 -24C>T polymorphism and methotrexate (MTX) toxicities in childhood ALL patients treated with high-dose MTX. A total of 112 Han Chinese ALL patients were treated with high-dose MTX according to the ALL-Berlin-Frankfurt-Muenster 2000 protocol. Our results showed that presence of the -24T allele in ABCC2 gene led to significantly higher MTX plasma concentrations at 48 hours after the start of infusion, which would strengthen over repeated MTX infusion. The -24T allele in ABCC2 gene was significantly associated with higher risks of high-grade hematologic (leucopenia, anemia, and thrombocytopenia) and non-hematologic (gastrointestinal and mucosal damage/oral mucositis) MTX toxicities. This study provides the first evidence that the -24T allele in ABCC2 gene is associated with the severity of MTX toxicities, which add fresh insights into clinical application of high-dose MTX and individualization of MTX treatment.

PMID:
24404132
PMCID:
PMC3880259
DOI:
10.1371/journal.pone.0082681
[Indexed for MEDLINE]

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