Bramanti S, De Philippis C, Bartoli A, et al. Feasibility and Efficacy of a Pharmacokinetics-Guided Busulfan Conditioning Regimen for Allogeneic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Adult Patients with Hematologic Malignancies. Transplantation and Cellular Therapy. 2021; 27 (11): 912.e1 (doi: 10.1016/j.jtct.2021.08.006).
A single-center study found that intravenous administration of pharmacokinetics (PK)-guided busulfan (Bu) as part of a thiotepa, Bu, and fludarabine (TBF) conditioning regimen provides effective treatment and feasible drug monitoring for adult patients with hematologic disorders. Researchers discovered an optimal Bu therapeutic window following I.V. administration, aiming for a target area under the curve (AUC) of 16,000 to 24,000 µM/minute. The study included, 41 adults with myeloid or lymphoid malignancies who received allogeneic stem cell transplantation with a PK-guided Bu-based reduced-toxicity conditioning regimen. The participants were administered a thiotepa, Bu, Fludarabine (TBF) with Bu monitoring to reach a target AUC of 16,000 µM/minute. It took a median of 23 days to achieve absolute neutrophil count recovery and 29 days for transfusion-independent platelet count recovery. Cumulative incidence (CI) of nonrelapse mortality was 7% at 100 days and 13% at 12 months. Six patients exhibited grade 3 liver toxicity, one patient developed sinusoidal obstruction syndrome at 27 days, and 18 developed grade 3 mucositis. The CI of ≥grade 3 infections was 29% at 30 days, 34% at 60 days, 44% at 100 days, and 56% at 12 months. A 15% CI of grade II-IV acute graft-versus-host disease (GVHD) was observed at 180 days, while the 1-year CI of overall chronic GVHD was 20%. During a median follow-up of alive patients at 14.4 months, the CI of relapse at 1 year was 6%. The 1-year rates of progression-free survival and overall survival were 81% and 84%, respectively.