Individualized Busulfan Dosing Improves Outcomes vs. Fixed Dosing in Pre-Transplant, MRD+, Intermediate-Risk AML Patients Receiving Allo-SCT

Individualized, pharmacokinetic (PK)-guided dosing of busulfan improved relapse rates, leukemia-free survival (LFS), and overall survival (OS) following allogeneic stem cell transplantation (allo-SCT), compared with fixed dosing, in patients with intermediate-risk acute myeloid leukemia who were in complete remission (CR) at the time of transplant. LFS was significantly improved in patients who were MRD positive by flow cytometry prior to transplant, but not those who were MRD negative, after individualized busulfan administration.

Of the 87 patients (48 male, median age 51) enrolled in the single-center retrospective study, 44 (51%) were MRD positive by flow cytometry prior to allo-SCT; 32 patients (37%) received PK-guided busulfan dosing. To optimize busulfan exposure, dosing was adjusted to achieve an area under the curve (AUC) within ±10% of the target (40, 60, or 89 mg*h/l). After a median follow-up of 27 months, 3-year relapses, LFS, and OS were significantly lower after individualized compared with fixed busulfan exposure. The study findings appeared in February in the European Journal of Haematology.

The study is the first to analyze the role of individualized busulfan administration in a homogeneous population of patients with intermediate-risk AML in CR prior to allo-SCT, write co-corresponding authors Nicolaus Kröger and Evgeny Klyuchnikov and colleagues at the University of Hamburg in Germany. “A randomized prospective study to evaluate impact of individualized [busulfan] administration on relapses and survival outcomes in larger cohort of patients focusing on MRD studies is warranted,” they conclude.

  • Klyuchnikov E, Langebrake C, Badbaran A, et al. Individualized busulfan dosing improves outcomes compared to fixed-dose administration in pre-transplant minimal residual disease-positive acute myeloid leukemia patients with intermediate-risk undergoing allogeneic stem cell transplantation in CR. Eur J Haematol. 2023;110(2):188-197. doi:10.1111/ejh.13893

Tags: MRD, MRD testing, measurable residual disease

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