Therapeutic Monitoring of Busulfan in Hematopoietic Stem Cell Transplantation

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Busulfan is an alkylating agent commonly used to ablate marrow before hematopoietic stem cell transplantation. High levels have been shown to increase the chance for severe hepatic veno-occlusive disease, for which there is no treatment and which can be fatal. Low levels are associated with recurrence of chronic myeloid leukemia, whereas even lower levels are associated with graft rejection. The therapeutic window for busulfan is narrow and disease and graft-source dependent. Busulfan concentration in plasma is readily assayed by gas chromatography. In the authors' center, busulfan levels determined from the first dose of the drug are used to adjust the dose to that selected to achieve the desired therapeutic outcome by the third dose of the 16-dose regimen. Thus, turnaround time is less than 6 hours. Analytical and pharmacokinetic aspects of busulfan therapeutic monitoring are described. The cost of pharmacokinetically targeting busulfan concentration is ≤1% of the cost of hematopoietic stem cell transplantation.

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