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Decitabine triphosphate levels in peripheral blood mononuclear cells from patients receiving prolonged low-dose decitabine administration: a pilot study

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Abstract

Purpose

Decitabine is a nucleoside analog used in the treatment for myelodysplastic syndrome. The compound requires intracellular conversion to its triphosphate to become active. Decitabine triphosphate has, however, never been quantified in peripheral blood mononuclear cells (PBMCs) from patients.

Method

This article describes a method for the quantitative determination of decitabine triphosphate in PBMCs using liquid chromatography coupled to tandem mass spectrometry. The method was applied to ex vivo incubated whole blood samples and samples from three patients receiving prolonged low-dose decitabine treatment.

Results

We successfully quantitated decitabine triphosphate in PBMCs. Considerable levels were detected in PBMCs from two patients that responded well to therapy, whereas only low levels were present in a non-responding patient. Moreover, the data show that, in contrast to plasma decitabine, intracellular decitabine triphosphate accumulates during a treatment cycle of nine infusions at a dose of 15 mg/m2.

Conclusions

The results suggest a relationship between decitabine triphosphate levels and response to therapy. Based on the observed accumulation of decitabine triphosphate during a treatment cycle, a less intensive dose scheme could be feasible.

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Authors and Affiliations

  1. Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands

    Robert S. Jansen, Hilde Rosing, Ron J. Keizer & Jos H. Beijnen

  2. Department of Haematology, Haga Hospital, Leyweg 275, 2545 CH, The Hague, The Netherlands

    Pierre W. Wijermans

  3. Division of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Jan H. M. Schellens

  4. Department of Pharmaceutical Sciences, Science Faculty, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands

    Jan H. M. Schellens & Jos H. Beijnen

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  1. Robert S. Jansen
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  2. Hilde Rosing
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  3. Pierre W. Wijermans
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  6. Jos H. Beijnen
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Correspondence to Robert S. Jansen.

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Jansen, R.S., Rosing, H., Wijermans, P.W. et al. Decitabine triphosphate levels in peripheral blood mononuclear cells from patients receiving prolonged low-dose decitabine administration: a pilot study. Cancer Chemother Pharmacol 69, 1457–1466 (2012). https://doi.org/10.1007/s00280-012-1850-x

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  • DOI: https://doi.org/10.1007/s00280-012-1850-x

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