Busulfan Interlaboratory Proficiency Testing Program Revealed Worldwide Errors in Drug Quantitation and Dose...

Area of Science:

• Pharmacokinetics and Therapeutic Drug Monitoring
• Hematopoietic Cell Transplantation (HCT)
• Clinical Chemistry and Laboratory Medicine

Background:

• Personalized busulfan dosing is key to improving clinical outcomes in hematopoietic cell transplantation (HCT).
• Previous proficiency tests indicated significant inaccuracies in busulfan dose recommendations.
• An interlaboratory proficiency test program was established to assess busulfan quantitation, pharmacokinetic modeling, and dosing.

Purpose of the Study:

• To evaluate the performance of laboratories in busulfan quantitation, pharmacokinetic modeling, and dose recommendations.
• To identify persistent challenges in achieving accurate busulfan plasma exposure targets.
• To inform potential regulatory or educational interventions for HCT centers.

Main Methods:

• A proficiency test scheme involving 5 rounds (2 rounds/year) with busulfan samples (low and high concentrations) and theoretical cases.
• Participating laboratories reported busulfan concentrations, pharmacokinetic modeling, and dose recommendations.
• Descriptive statistics were used to assess accuracy within ±15% for concentrations and ±10% for plasma exposure.

Main Results:

• An average of 78% of busulfan concentration measurements were accurate across 41 participating laboratories.
• Area under the concentration-time curve calculations were accurate in 75%-80% of cases.
• Dose recommendations showed lower accuracy (60%-69%), with some laboratories consistently deviating from reference values.

Conclusions:

• The proficiency test highlights ongoing inaccuracies in busulfan quantitation, pharmacokinetic modeling, and dose recommendations.
• Current educational efforts appear insufficient, suggesting a need for regulatory oversight.
• Mandatory participation in busulfan proficiency testing or use of specialized labs may be required for HCT centers.