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Monitoring of Busulphan Concentrations in Children Undergone Hematopoietic Stem Cell Transplantation: Unicentric Experience over 10 years

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

Background and Objectives

The aim of this report is to describe the experience in the management of busulphan-based conditioning regimen administered before hematopoietic stem cell transplantation (HSCT) in children.

Methods

We report the values of the first dose AUC (area under the concentration-time curve, normal target between 3600 and 4800 ng·h/mL) in children treated with oral and intravenous busulphan, and we analyze the impact of some clinical variables in this cohort of patients.

Results

82 children treated with busulphan before HSCT were eligible for the study: 57 received oral busulphan with a mean AUC of 3586 ng·h/mL, while 25 received intravenous busulphan with a mean AUC of 4158 ng·h/mL. Dose adjustment was based on first dose AUC. The dose was increased in 36 children (43.9%) and decreased in 26 patients (31.7%). Age at HSCT (P = 0.015), cumulative dose of busulphan as mg/m2 (P < 0.001), busulphan dose prescribed as mg/Kg (P = 0.001), intravenous busulphan administration (P < 0.001), type of stem source cells (P = 0.016), and type of HSCT (P = 0.03) were associated with AUC levels. No statistically significant differences were found between transplant-related toxicity, acute and chronic graft versus host disease, engraftment, and AUC levels.

Conclusions

We concluded that older age at HSCT, intravenous administration of busulphan, cumulative, and prescribed dose of busulphan are associated with higher AUC levels. The absence of significant correlations between toxic events, graft failure, and AUC suggests the efficacy of busulphan concentrations monitoring in our patients.

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Acknowledgements

The authors thank Mrs. Manuela Rescali for her help in the preparation of this paper.

Author information

Authors and Affiliations

  1. Hematopoietic Stem Cell Transplant Unit, Department of Hematology–Oncology, Istituto G. Gaslini, Largo G. Gaslini, 5, 16147, Genoa, Italy

    Maura Faraci, Edoardo Lanino, Stefano Giardino, Massimiliano Leoni & Daniela Di Martino

  2. Epidemiology Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Carmine Tinelli & Annalisa De Silvestri

  3. Pediatric Department, Istituto G. Gaslini, Genoa, Italy

    Marta Ferretti

  4. Infectious Diseases Unit, Istituto G. Gaslini, Genoa, Italy

    Elio Castagnola

  5. Clinical and Experimental Pharmacokinetic Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Monica Broglia & Antonella Bartoli

Authors
  1. Maura Faraci
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  2. Carmine Tinelli
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  3. Edoardo Lanino
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  4. Stefano Giardino
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Corresponding author

Correspondence to Maura Faraci.

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Funding

The authors declare no source of funding.

Conflict of interest

Maura Faraci, Carmine Tinelli, Edoardo Lanino, Stefano Giardino, Massimiliano Leoni, Marta Ferretti, Elio Castagnola, Monica Broglia, Annalisa De Silvestri, Daniela Di Martino, and Antonella Bartoli declare that they have no conflict of interest.

Ethics approval

All procedures in this study were in accordance with the 1964 Helsinki Declaration (and its amendments). Ethics committee (Comitato Etico Regionale–Regione Liguria–IRCCS AOU San Martino–IST) approves data collection from medical records of patients admitted to our department aim at retrospective studies (360REG2014).

Informed consent

Written informed consent is not required, because monitoring of busulphan is included in common good clinical practice.

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Faraci, M., Tinelli, C., Lanino, E. et al. Monitoring of Busulphan Concentrations in Children Undergone Hematopoietic Stem Cell Transplantation: Unicentric Experience over 10 years. Eur J Drug Metab Pharmacokinet 43, 173–181 (2018). https://doi.org/10.1007/s13318-017-0431-0

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  • DOI: https://doi.org/10.1007/s13318-017-0431-0

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