Background and importance Busulfan is a chemotherapeutic drug used in preparative regimens for hematopoietic stem cell transplantation in adults and children for different diseases. Its efficacy and safety could be affected by its narrow therapeutic range and its pharmacokinetic variability, making therapeutic drug monitoring essential to optimise treatments.

Aim and objectives To analyse the impact of therapeutic drug monitoring on busulfan treatments in our centre during the last 10 years.

Material and methods We conducted a retrospective observational study in paediatric patients treated with intravenous busulfan between 2010 and 2020 in a bone marrow transplantation unit.

We recorded demographics (age, sex, weight, baseline disease), treatment (type of conditioning protocol, dose by weight), drug monitoring (need for dose modification, number of necessary adjustments, percentage of variation between received dose and theoretical dose), efficacy (incidence of implant failure) and safety variables (incidence of sinusoidal obstruction syndrome).

For pharmacokinetic studies we applied a nonlinear regression method and used ID3 software. Area under the curve target was 55 000–95 000 ng/mL×hour, depending on the conditioning protocol (reduced intensity or myeloablative).

Results We included 45 patients with ages between 4 months and 16 years. They received 43 allogeneic and two autologous transplantations. Baseline diseases in the allogeneic group were 23 malignant and 20 non-malignant haematological diseases while in the autologous group there were two neuroblastomas. Regarding the conditioning regimen, 38/45 were myeloablative and 7/45 non-myeloablative.

Busulfan initial doses ranged from 3.2 and 5.1 mg/kg/day (related to adjusted body weight), according to the protocol and the weight band. All patients received seizures prophylaxis.

Eight patients presented implant failure (five received myeloablative conditioning). Four patients presented sinusoidal obstruction syndrome (all received myeloablative conditioning).

Conclusion and relevance These data show high variability in the direction and magnitude of adjustments made to assure a busulfan exposure within the desired range. Busulfan monitoring is an essential tool to optimise treatments and to improve its efficacy and safety.

Conflict of interest No conflict of interest