© 2010 American Association for Clinical Chemistry, Inc.
Clinical Case Study |
Commentary
Children’s Hospital, Boston, MA.
aAddress correspondence to the author at: Children’s Hospital, Farley 720, 300 Longwood Ave., Boston, MA 02115. Fax 617-730-0383; e-mail mark.kellogg{at}childrens.harvard.edu.
Although the development of a parenteral formulation for busulfan by Bhagwatwar et al. in 1996 (1) dramatically improved the ability to achieve desired plasma concentrations and reduced the incidence of such complications as sinusoidal obstruction syndrome and engraftment failure, there are several groups that do not "fit" the population-based PK models. In addition to the obese patient population and cases of coadministered drugs (as seen in this case), patients with thalassemia, pediatric patients under the age of 4 years, those with lysosomal-storage diseases, and polymorphisms of glutathione S-transferase are just some examples of the groups that require closer monitoring during busulfan treatment.
The logistics and costs associated with PK analysis continue to drive efforts investigating more efficient means to estimate busulfan dose (2)(3)(4). Careful consideration of the data from these studies is important. Previous studies have suffered from the limited number and diversity of the patients studied. A critical assessment of how an institution’s patient population and practices differ from those of the studies requires participation of the entire treatment team, including the laboratory scientist’s knowledge of preanalytical and analytical variables.
The case presentation briefly mentions the fact that improper sample collection can alter busulfan PK. This issue is particularly important when a patient is receiving high-dose intravenous busulfan, and it is probably the first thing laboratorians should investigate when discrepant results arise. The use of multilumen catheters is typical in busulfan regimens, and it is critical that the laboratory educate clinical staff on the importance of correct and consistent blood collection procedures. Given the number of blood collections and infusions associated with busulfan dosing, it is very tempting to infuse and collect through the same lumen if one lumen loses patency during the process. This practice will probably become even more problematic as institutions move to outpatient-based and once-daily infusion models for busulfan regimens.
This case study highlights the role of the clinical laboratory scientist in interpreting therapeutic drug monitoring data. This individual must not only have knowledge of PK, pharmacodynamics, and principles of therapeutic drug monitoring but also have active interaction with clinicians.
Acknowledgments
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors’ Disclosures of Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
References
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- Vassal G, Michel G, Esperou H, Gentet JC, Valteau-Couanet D, Doz F, et al. Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring. Cancer Chemother Pharmacol 2008;61:113-123.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
- Tse WT, Duerst R, Schneiderman J, Chaudhury S, Jacobsohn D, Kletzel M. Age-dependent pharmacokinetic profile of single daily dose i.v. busulfan in children undergoing reduced-intensity conditioning stem cell transplant. Bone Marrow Transplant 2009;44:145-156.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
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