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Busulfan clearance does not predict the development of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation

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Abstract

Hepatic veno-occlusive disease (VOD) is a life-threatening complication following hematopoietic stem cell transplant (HSCT). Busulfan has a narrow therapeutic index and its concentration was found to correlate with VOD. Our primary objective was to assess the association between busulfan clearance and VOD in HSCT patients. In this retrospective analysis, we included patients who received their HSCT between 2003 and 2014 and followed at Sultan Qaboos University Hospital. All patients who received dose-targeted busulfan-containing conditioning were included. Target steady-state concentration (Css) was 800–900 ng/ml. VOD was assessed using modified Seattle criteria. The impact of busulfan clearance on VOD was analyzed using univariable logistic regression model. Seventy-three patients were included with a mean age of 15 years. Of those, 47% were transplanted for hematological malignancies and 53% for inherited hemoglobinopathies. Target Css was achieved in 85% of patients. The rate of VOD was 17%. There was no significant impact of busulfan clearance (p = 0.919) or area-under-the-concentration–time-curve (p = 0.275) on VOD. Targeting busulfan Css into narrow therapeutic range may have accounted for the findings. The risk of VOD might be related to other factors such as the genetic background, and more studies are required to investigate these factors.

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Authors and Affiliations

  1. Pharmacy Department, Sultan Qaboos University Hospital, Muscat, Oman

    Bushra Salman

  2. Department of Hematology, Sultan Qaboos University Hospital, Muscat, Oman

    Murtadha Al-Khabori, Mohammed Al-Huneini & David Dennison

  3. Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman

    Abdulhakeem Al-Rawas

  4. Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman

    Mohammed Al-Za’abi

Authors
  1. Bushra Salman
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  2. Murtadha Al-Khabori
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  3. Mohammed Al-Huneini
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  4. Abdulhakeem Al-Rawas
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  5. David Dennison
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  6. Mohammed Al-Za’abi
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Correspondence to Murtadha Al-Khabori.

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We declare that there is no conflict of interest related to the subject matter discussed in this manuscript. We also clarify that we have full control of all the primary data.

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Salman, B., Al-Khabori, M., Al-Huneini, M. et al. Busulfan clearance does not predict the development of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation. Int J Hematol 112, 210–216 (2020). https://doi.org/10.1007/s12185-020-02891-0

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  • DOI: https://doi.org/10.1007/s12185-020-02891-0

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