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International Journal of Hematology

, Volume 98, Issue 6, pp 702–707 | Cite as

Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy

  • Masakatsu YanagimachiEmail author
  • Hiroaki Goto
  • Tetsuji Kaneko
  • Takuya Naruto
  • Koji Sasaki
  • Masanobu Takeuchi
  • Reo Tanoshima
  • Hiromi Kato
  • Tomoko Yokosuka
  • Ryosuke Kajiwara
  • Hisaki Fujii
  • Fumiko Tanaka
  • Shoko Goto
  • Hiroyuki Takahashi
  • Masaaki Mori
  • Sumio Kai
  • Shumpei Yokota
Original Article

Abstract

High-dose methotrexate therapy (HD-MTX) has been well established for the treatment of childhood acute lymphoblastic leukemia (ALL). The aims of this study were to investigate whether clinical and pharmacogenetic factors influence plasma MTX concentration and renal dysfunction in patients treated with HD-MTX. In a total of 127 courses of HD-MTX in 51 patients with childhood ALL, influence of clinical and pharmacogenetic factors on plasma MTX concentration and HD-MTX-related renal dysfunction was evaluated. Clinical factors included age, gender, duration of HD-MTX continuous-infusion and duration of pre-hydration before HD-MTX. Pharmacogenetic factors included 5 gene polymorphisms within the MTX pathway genes, namely, SLC19A1, MTHFR, ABCC2 and ABCG2. Short duration of pre-hydration before HD-MTX is the most important risk factor for prolonged high MTX concentration (p < 0.001, OR 6.40, 95 % CI 2.39–17.16) and renal dysfunction (p = 0.013, OR 3.15, 95 % CI 1.27–7.80). The T allele at MTHFR C677T was the risk factor for prolonged high MTX concentration (p = 0.009, OR 5.54, 95 % CI 1.54–19.85), but not for renal dysfunction. We found the influence of MTHFR C677T polymorphism on prolonged high MTX concentration. We reconfirmed the importance of adequate pre-hydration before HD-MTX to prevent prolonged high MTX concentration and MTX-related renal dysfunction.

Keywords

Pre-hydration Plasma concentration Renal toxicity High-dose methotrexate Methylentetrahydrofolate reductase (MTHFR) 

Notes

Acknowledgments

We are grateful to Teddy Kamata for his careful linguistic assistance with this manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12185_2013_1464_MOESM1_ESM.doc (99 kb)
Supplementary material 1 (DOC 99 kb)

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Copyright information

© The Japanese Society of Hematology 2013

Authors and Affiliations

  • Masakatsu Yanagimachi
    • 1
    Email author
  • Hiroaki Goto
    • 1
  • Tetsuji Kaneko
    • 2
  • Takuya Naruto
    • 1
  • Koji Sasaki
    • 1
  • Masanobu Takeuchi
    • 1
  • Reo Tanoshima
    • 1
  • Hiromi Kato
    • 1
  • Tomoko Yokosuka
    • 1
  • Ryosuke Kajiwara
    • 1
  • Hisaki Fujii
    • 1
  • Fumiko Tanaka
    • 3
  • Shoko Goto
    • 3
  • Hiroyuki Takahashi
    • 3
  • Masaaki Mori
    • 1
  • Sumio Kai
    • 3
  • Shumpei Yokota
    • 1
  1. 1.Department of PediatricsYokohama City University Graduate School of MedicineYokohamaJapan
  2. 2.Department of Biostatistics and EpidemiologyYokohama City University Graduate School of MedicineYokohamaJapan
  3. 3.Department of PediatricsSaiseikai Yokohamasi Nanbu HospitalYokohamaJapan

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