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Evaluation of the Pharmacokinetics and Efficacy of a Busulfan Test Dose in Adult Patients Undergoing Myeloablative Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 2017 Jun;23(6):952-957



Pubmed ID




Scopus ID

2-s2.0-85017516033   11 Citations


Owing to interpatient variability in busulfan exposure, therapeutic monitoring of busulfan is often used in myeloablative allogeneic transplantation to ensure that patients are near the optimal steady-state goal of 900 ng/mL. One challenge in therapeutic monitoring of busulfan is the brief course of busulfan treatment, requiring prompt analysis and dose adjustments as needed. Pharmacokinetic evaluation of a busulfan test dose before the start of the conditioning regimen would allow for all conditioning regimen doses to be given at the calculated optimized dose. An observational study was completed to evaluate the effects of a busulfan test dose of 0.9 mg/kg administered before the start of a myeloablative intravenous busulfan-based conditioning regimen. Sixty adult patients who received a busulfan conditioning regimen were reviewed, including 30 patients prior to the implementation of the busulfan test dose (pretest dose group) and 30 patients who received the busulfan test dose (posttest dose group). The primary objective was a pharmacokinetic evaluation of the percentage of patients who achieved the desired steady-state goal using the test dose strategy. The safety and efficacy of the busulfan test dose were evaluated as well. The average busulfan steady-state level after the first dose of the conditioning regimen was significantly lower in the pre-test dose group compared with the post-test dose group (660 ng/mL versus 879.9 ng/mL; P < 0.001). Compared with the post-test dose group, significantly fewer patients in the pre-test dose group were within 10% of the busulfan steady-state goal (10% versus 73.3%; P < 0.001) or within 5% of the goal (0% versus 53%; P < 0.001). Requirements for parenteral nutrition and/or patient-controlled analgesia owing to mucositis and rates of veno-occlusive disease were not significantly different between the pre-test dose group and the post-test dose group. The rates of disease relapse, mortality, and acute graft-versus-host disease were similar in the two groups. A pretransplantation busulfan test dose of 0.9 mg/kg improved the patients' ability to reach therapeutic busulfan target levels after the first conditioning dose and resulted in fewer adjustments during conditioning. The use of a busulfan test dose did not significantly increase patients' risk of mucositis or other safety outcomes.

Author List

Weil E, Zook F, Oxencis C, Canadeo A, Urmanski A, Waggoner M, Eastwood D, Pasquini M, Hamadani M, Hari P


Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Dose-Response Relationship, Drug
Drug Monitoring
Hematopoietic Stem Cell Transplantation
Maximum Tolerated Dose
Middle Aged
Myeloablative Agonists
Transplantation Conditioning
Treatment Outcome
Young Adult
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a