Fixed-dose administration and pharmacokinetically guided adjustment of busulfan dose for patients undergoing hematopoietic stem cell transplantation: a meta-analysis and cost-effectiveness analysis.

This study aims to evaluate the efficacy, safety, and long-term cost-effectiveness of fixed-dose busulfan (Bu) administration and pharmacokinetically (PK) guided adjustment of Bu dose for patients who underwent hematopoietic stem cell transplantation. The efficacy and safety of both dosing strategies were compared using a systematic review and meta-analysis. A Markov model was used in estimating relevant cost and health outcomes from the perspective of the health system. The primary outcomes of interest were lifetime cost, quality adjusted life-years (QALYs) gained, and incremental cost-effectiveness ratio (ICER) in dollar per QALY gained. Results showed that progression-free survival and overall survival in the PK-guided group were higher than that in the fixed-dose group, and the PK-guided group was associated with low non-relapse mortality and relapse rate. In contrast to safety, the incidence of acute graft-versus-host disease (GVHD) was the same in the two groups (P > 0.05). Cost-effectiveness analysis showed that the QALY of the PK-guided group (12.8135 QALYs and $582,475.07) increased by 2.0609 relative to that in the fixed-dose group (10.7526 QALYs and $562,833.20), and the ICER was $9530.72/QALY. One-way and probability sensitivity analyses confirmed the reliability of the results. In conclusion, the PK-guided approach has higher efficacy and is safer.