DP100 | BUSULFAN PHARMACOKINETIC-GUIDED CONDITIONING REGIMEN FOR ALLOGENEIC STEM CELL TRANSPLANTATION IN ADULTS PATIENTS: RESULTS FROM A SINGLE CENTER

Busulfan (BU) is an alkylating agent with a large pharmacokinetic (PK) variability.After IV administration, an optimal BU therapeuticwindow, measured as Area Under Curve(AUC) between 16.000 and 24.000 μM x min hasbeenidentified.PK-guided BUdosingwas demonstrated to improveoverall (OS) and progression-free survival (PFS) compared with fixed dose administration. In this study,we evaluated the PK-guided BU-based conditioning regimens in 54 patients undergoing allogeneic stem cell transplantation (allo-SCT) and compared to those with fixed dosage (no PK-BU).BU exposure was calculated using AUC measurements. The target AUC16 was reserved for patients aged 65-70 years and thosewith HCT-CI ≥3. PK was measured after the first fixed dose of BU (100 mg/m2) and after the 3rd dose.GVHD prophylaxis was related to the donor type. Primary endpoints are day +100 and 1-year no-relapse mortality (NRM)and1-y relapse free-survival (RFS). From October 2022 and December 2024, 54patients were included in the PK-BU cohort while 150 patients received fixed dose BU (from 2015 and 2021).Patient characteristics were reported in Table. The median follow-up was 8 months(1-19 months) in the PK-BU cohort and 32.5 months (5-95 months) in fixed-BU.In PK-BU cohort, 37 patients (68%) received BU AUC16 and 17 (31%)BU AUC20.No patients presented graft failure in the PU-BK cohort and 2.6% in the fixed-BU cohort (4/150), the median time to safe neutrophil and platelet count was both 18 days in PK-BU cohort,while in the BU-fixed was 20 and 17 days, respectively. In the PK-BU, the cumulative incidence (CI) of aGVHD grade 2-4 and 3-4 was 15% and 2%; CI moderate-severe cGVHD was 5%, while in fixed dose BU were 24%, 8%, and 14%, respectively. In the PK-BU, 100-day and 1-y NRM were 15% and 26% and in fixed dose BU were 11% and 22%, respectively. In the PK-BU, 1-y RFS was 56% and in the fixed dose BU 53%.In the PK-BU, 1-y OS was 68% and 66% in fixed dose BU. In the PK-BU, the incidence of grade 3-4 mucositis was 35% (19/54); the incidence of transplant-associated-thrombotic microangiopathyand veno-occlusive disease was 13% (7/54)and 7% (4/54), respectively. In this study, PK-guided BU-based conditioning regimen demonstrated to be safe and effective for patients undergoing allo-SCT. Individualized dosing may reduce the incidence of acute and chronicGVHD.