High-dose busulfan (BU) is the cornerstone of conditioning regimens prior to HSCT in children. The relation of BU exposure and event-free survival (EFS) is not clear due to conflicting reports especially in pediatric patients The cum AUC (mg × h/L ) exposure targets for BU were : EMA: 59–99 ; US-FDA: 59–89 Bartelink IH et al. 1: 78-101 mg × h/L Better EFS with cumAUC of <57.6 or between 57.6 - 67.2 mg × h/L1,2,3 cumAUC of 86.4 mg × h/L showed better EFS, in pediatric patients4 All these studies were evaluated retrospectively with a sample size varying from 45 to <100 patients. No clear consensus among peers about the utility of BU cumAUC as an indicator of EFS Is there any other dynamic indicator/marker of BU efficacy ? Background References 1. Bartelink et al., Lancet Haematol. 2016; 3: e526-e536 2. Ansari et al., Ther Drug Monit 2014;36:93-99 3. Baker et al., Bone Marrow Transplant 2000; 26,:607–614 3. 4. Maheswari et al., Bone Marrow Transplantation 2014: 49, 366–369. 5. McCune et al., Bone Marrow Transplant. 2002;30(3):167-73. Results Methods Conclusion The BU MR (BU/SU) on day 3 above 4.973 and 25.06 were associated with worse EFS in children undergoing HSCT and received BU in QID and QD dosing schedules, respectively. Predictive nature of MRs measured were replicated in two different BU dosing schedules followed. These observations deserve attention and need to be replicated in a larger study, especially in an external cohort to rule out any unidentified bias in this analysis. 44 received BU four times daily (QID) and 13 received BU once daily (QD; (n=13; 10 allogeneic HSCTs and 3 autologous HSCT). BU/SU = MR was measured on the 3rd day of conditioning. EFS was defined from the time of transplant until death, relapse, or rejection, whichever occurred first. Chakradhara Rao S Uppugunduri1,2, Aziz Rezgui3, Patricia Huezo-Diaz Curtis1,2, Tiago Nava1,2, Simona Mlakar1,2, Yves Theoret4, Henrique Bittencourt5, Maja Krajinovic3, Marc Ansari1,2 Busulfan/Sulfolane metabolic ratio on the third day of conditioning may predict the event-free survival in children receiving busulfan based conditioning prior to hematopoietic stem-cell transplantation Huezo‐diaz P & Uppugunduri CRS et al., CDM, 2014; 15:251‐264 Objective: To evaluate the utility of BU MR (busulfan/sulfoalne,SU) to predict event-free survival (EFS) in children undergoing HSCT, retrospectively. Four times daily BU (n=44) Events occured No Events N (%) N(%) Gender Male 7 (31.8) 15 (68.2) Female 10 (45.5) 12 (55.5) Diagnosis (S) Malignancies (ALL, AML, MDS) 16 (59.3) 11 (40.7) Non‐ malignancies (/HP, ID, Met Dis,) 1 (5.9) 16 (94.1) Disease Status (Leukemia) (T) CR1 6 (60) 4 (40) CR2 / CR3 / Relapse 4 (80) 1 (20) HLA compatibility MUD 3 (57.1) 4 (42.9) MRD 3 (21.4) 11(78.6) MM RD 2 (66.7) 1 (33.3) MM UD 9 (45) 11 (55) Stem Cell Source BM 5 (27.8) 13 (72.2) Cord Blood 12 (46.2) 14 (53.8) Conditioning Bu/Cy 16 (39) 25 (61) Bu/Cy/VP16 1 (50) 1 (50) Bu/Mel 0 1 (100) Serotherapy ATG 13 (37.1) 22 (62.9) None 4 (44.4) 5 (55.6) Mean (SD) Mean (SD) Age (years) 8.9 (4.9) 6.2 (5.94) Weight (Kg) 35.1 (20.9) 22.7 (18.5) Once daily BU (n=13) Events occured No Events N N Gender Male 1 3 Female 6 3 Diagnosis (S) Malignancies (ALL, AML, MDS) 6 2 Non‐malignancies (/HP, ID, Met Dis,) 1 4 Disease Status (Leukemia) (T) CR1 3 0 CR2 / CR3 / Relapse 2 0 Partial Remission 1 1 HLA compatibility MUD 1 0 MRD 1 5 MM RD ‐ ‐ MM UD 3 0 Stem Cell Source BM 1 3 Cord Blood 4 2 PBSC (AUT) 2 1 Conditioning Bu/Cy 2 3 Bu/Flu 3 2 Bu/Mel 2 1 serotherapy ATG 3 4 None 4 2 Mean (SD) Mean (SD) Age (years) 6.1 (5.6) 7.4 (4.7) Weight (Kg) 17.4 (2.6) 17.0 (1.4) 1University Hospitals of Geneva, Onco‐Hematology Unit, Department of Pediatrics, Geneva, Switzerland, 2CANSEARCH Research Laboratory, Faculty of Medicine, University of Geneva, Geneva, Switzerland, 3Charles‐Bruneau Cancer Center, CHU Sainte‐Justine Research Center, Montreal, Canada, 4Charles‐Bruneau Cancer Center, Department of Pharmacology and Physiol