Annals of hematology
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Annals of hematology · Dec 2018
Multicenter Study Clinical TrialThe pharmacokinetics and pharmacodynamics of busulfan when combined with melphalan as conditioning in adult autologous stem cell transplant recipients.
Busulfan (Bu) is an alkylating agent widely used in conditioning regimes prior to stem cell transplantation (SCT), most commonly in combination with cyclophosphamide (Bu-cy) or fludarabine (Bu-flu) as myeloablative conditioning prior to allograft or with high-dose melphalan (Bu-mel) prior to autologous SCT. Despite many decades of Bu use, initially orally but now intravenously (IV), a paucity of pharmacokinetic (PK) and pharmacodynamic (PD) data exists to inform evidence-based guidelines as how best to balance the efficacy and toxicity of this agent. This is a non-randomized retrospective real-world study at three hospitals investigating the role of PK guidance in dosing Bu in the setting of IV Bu-mel autologous SCT. ⋯ On D-5, within the weight-based cohort, the mean AUCs were 12% higher than anticipated based on initial D-7 PK. No correlation between AUC and grade 3-4 transplant-related toxicities were observed, although only three patients had AUCs > 6000 μmol min/day. These results suggest that PK-directed Bu dosing may be of benefit in achieving a target level of drug exposure, with larger studies needed to determine the clinical significance of this strategy.