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Individual Dose Adjustment of Oral Busulfan Using a Test Dose in Hematopoietic Stem Cell Transplantation

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Abstract

Maintaining the appropriate average steady-state plasma concentrations (Css) of busulfan (BU) is critical for both successful engraftment and minimizing toxicity in hematopoietic stem cell transplantation (HST). We therefore performed a prospective trial with 50 adult Japanese patients that involved adjusting the BU dose in accordance with individual BU phar-macokinetics (PK). After administering a 0.5-mg/kg test dose of oral BU, we analyzed individual BU PK parameters and calculated an adjusted BU dose that would achieve a target BU Css of 850 ng/mL. Thirty-nine patients (78%) required a BU dose decrease, and the median adjusted BU dose was 0.81 mg/kg (range, 0.51–1.29 mg/kg). All patients who underwent allogeneic HST received the adjusted BU dose. After administering the sixth BU dose, we measured the plasma BU concentration. The actual BU concentration was significantly correlated with the expected BU concentration, and the predictability of the BU Css was 103% ± 19%. The incidence of toxicity excluding oral mucositis was low, and there was no regimen-related toxicity-associated mortality. Engraftment was achieved in 98% of the patients. This study showed that our method for adjusting the BU dose facilitated reliable prediction of the actual BU Css and that individualized BU dose adjustment was able to improve clinical outcomes in HST recipients treated with a BU-containing conditioning regimen.

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Authors and Affiliations

  1. First Department of Internal Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, 8140180, Fukuoka, Japan

    Yasushi Takamatsu, Junji Suzumiya & Kazuo Tamura

  2. Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan

    Noriaki Sasaki, Kentaro Ogata & Shuuji Hara

  3. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    Tetsuya Eto

  4. First Department of Internal Medicine, Kyushu University, Fukuoka, Japan

    Koji Nagafuji

  5. Third Department of Internal Medicine, Kyushu University, Fukuoka, Japan

    Yasunobu Abe

  6. Department of Hematology, Kyushu Cancer Center, Fukuoka, Japan

    Ilseung Choi

Authors
  1. Yasushi Takamatsu
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  2. Noriaki Sasaki
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  3. Tetsuya Eto
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  4. Koji Nagafuji
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  5. Yasunobu Abe
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  6. Ilseung Choi
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  7. Kentaro Ogata
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  8. Shuuji Hara
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  9. Junji Suzumiya
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  10. Kazuo Tamura
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Corresponding author

Correspondence to Yasushi Takamatsu.

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Takamatsu, Y., Sasaki, N., Eto, T. et al. Individual Dose Adjustment of Oral Busulfan Using a Test Dose in Hematopoietic Stem Cell Transplantation. Int J Hematol 86, 261–268 (2007). https://doi.org/10.1532/IJH97.07013

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  • DOI: https://doi.org/10.1532/IJH97.07013

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