Assessment of minimum discard volume for central venous catheter sampling: Validation via busulfan therapeutic drug monitoring in pediatric transplant patients.

Purpose: Frequent blood sampling in pediatric patients, particularly during hematopoietic stem cell transplantation (HSCT), can lead to significant cumulative blood loss and increase the risk of iatrogenic anemia. This study aimed to evaluate whether reducing the discard volume prior to blood sampling affects the accuracy of plasma Busulfan concentration measurements in this vulnerable population. Patients and methods: This prospective cohort study enrolled thirteen pediatric patients receiving HSCT at a tertiary children's hospital in China between July and October 2024. Blood samples were collected via double-lumen central venous catheters at seven time points (T0-T6) after the fourth dose of Busulfan, using four different discard volumes (1, 2, 3, and 4 mL). Each patient contributed repeated measurements under all four discard-volume conditions, resulting in 364 samples. Paired analyses were used to account for the within-patient repeated-measures design, and AUC non-inferiority was assessed against the prespecified 6% margin using the lower bound of the two-sided 95% confidence interval for the paired differences. Results: Using paired within-patient analyses, no significant differences in plasma Busulfan concentrations were observed among the discard-volume conditions. Paired differences between reduced discard volumes (1, 2, and 3 mL) and the 4 mL reference remained small, with 95% confidence intervals demonstrating consistent agreement. AUC non-inferiority analysis showed that the reduced discard-volume approaches remained within the prespecified 6% non-inferiority margin. ICC demonstrated excellent agreement between the reduced discard-volume conditions and the 4 mL reference for both individual time-point concentrations (ICC > 0.95) and AUC values. Bland-Altman analysis showed consistent agreement, with differences evenly distributed within the calculated 95% limits of agreement. Conclusion: A minimal discard volume of 1 mL demonstrated non-inferior accuracy compared with the standard 4 mL discard volume for determining plasma Busulfan levels and overall drug exposure during therapeutic drug monitoring. Implementing this approach may reduce cumulative discarded blood volume by up to 21 mL per patient during the seven sampling time points; however, the direct effect of reduced discard volume on anemia or transfusion requirements was not evaluated. This study adhered to the STROBE guidelines for observational research, and no patient or public contribution was involved.