8535 Background: Oral busulfan (Bu) clearance is highly variable in children and increased in the youngest. Thus, higher doses in children ≤4 y allowed to reach a similar exposure (AUC). Nevertheless, therapeutic drug monitoring (TDM) and dose-adjustments are needed to control the Bu AUC variability. An IV Bu form was developed. In a first trial, 24 children received an IV Bu dosing equivalent to the oral one (1.0 mg/kg ≤ 4 y, 0.8 mg/kg > 4 y). A retrospective pharmacokinetic (PK) modelling demonstrated body weight (BW) better than age for dose calculation. A new dosing was developed. [Nguyen L. et al., BMT 2004] Methods: It was evaluated in a representative pediatric population receiving Bu/Melphalan or Bu/Cyclophosphamide as a conditioning regimen before autologous or allogeneic transplantation, respectively. No dose adjustment was allowed and PK was performed at doses 1, 9 and 16. Bayesian Bu AUCs were calculated. Results: Today’s results (55 patients, median age 6 y [0.3 - 17.2], 20 patients ≤ 4 y) demonstrated the dosing performance to target the “therapeutic window”. All AUCs were >847 μM.min (engraftment threshold), 84% <1500 μM.min (hepatic veno-occlusive disease threshold) and all <2100 μM.min. Advantage of this new dosing over the previous age-based one is obvious. Large inter-patient variability (CV = 50%) on Bu clearance was confirmed but similar AUCs were achieved whatever the age. AUC inter-patient variability was 2.5-fold-reduced (CV ≤ 20%). Low intra-patient variability enabled reproducible exposure without the constraining and invasive use of TDM in children. Preliminary clinical results supported the PK benefit of the new IV Bu dosing: all patients engrafted, no death at Day+100 post-transplant, no severe HVOD (McDonald criteria). Conclusions: Body-weight-based calculation of IV Bu fixed dose can successfully target a therapeutic AUC in children without any dose-adjustment and PK monitoring. No significant financial relationships to disclose.