Speaker
Description
Haematopoietic cell transplantation (HCT) is a potentially curative treatment for leukaemia. Pre-transplant conditioning plays a central role in the successful outcome of allogeneic HCT and requires the administration of myeloablative drugs at a high dose. Busulfan is the backbone of such conditioning regimens in both adults and children. Busulfan is an alkylating agent with a narrow therapeutic window and unpredictable inter-individual and intra-individual variability on pharmacokinetics (PK). HD busulfan is administered via several injections (three to 16) to achieve a cumulative plasma exposure (area under the curve, AUC) associated with severe aplasia without triggering life-threatening toxicities, such as multi-organ failure or veno-occlusive disease. With regard to the PK variability of Busulfan, adaptive dosing should help reduce the risk of toxic death while ensuring adequate exposure to achieve clinical efficacy. This can be achieved using either a mechanistic, bottom-up approach or top-down, phenomenological modelling. By developing dedicated population pharmacokinetics (pop-PK) approaches in our institute, it was possible to set up a sampling plan to collect blood samples for therapeutic drug monitoring based upon a first standard administration. This allows us to identify individual PK parameters, derive exposure and calculate a customised dose of Busulfan for the remaining administrations, thereby maintaining the patient within the desired target. We will present how this strategy can be successfully implemented at the bedside for both adults and children, and demonstrate how it translates into correcting plasma exposure to the target and improved clinical outcome eventually.
Bibliography
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year={2025},
publisher={Wiley Online Library}
}
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publisher={MDPI}
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}
