Intravenous (IV) busulfan has been developed to overcome variable absorption of oral busulfan and tested in several trials. We tested its pharmacological properties and tolerability in 16 Korean SCT patients. IV busulfan was administered at 0.8 mg/kg every 6 hours for a total of 16 doses (days -7 to -4), which was followed by cyclophosphamide administration at 60 mg/kg every 24 hours for 2 days (days -3 and -2). The median AUCinf values (at the 1st dose) and AUCss (at the steady state) were 1060.4 mM·min (range: 511.1– 1812.7) and 1092.5 mM·min (range: 539.7 – 1560.8), respectively. All patients had an AUCinf of < 1500 mM·min at the 1st dose, and 13 of the 16 (81.3 %) maintained AUCss levels between 800 and 1500mM·min. Overall, pharmacokinetics of IV busulfan in our SCT patients appeared comparable to those observed in other study. Thirteen of 16 patients achieved successful engraftments but 4 patients (25%) developed hepatic VOD (2 of which were fatal). Although there was no apparent correlation between AUC and hepatic VOD development, 3 out of 4 patients with VOD had advanced disease at the time of SCT. Notably, patients who had uncontrolled diseases (CML blast crisis, ALL 2nd relapse) succumbed to VOD and those who survived VOD had less advanced disease (CML CP, ALL in 2nd CR) at the time of SCT. In conclusion, pharmacokinetics of IV busulfan in our SCT patients appeared comparable to those observed in other studies, however, hepatic VOD was still a major morbidity, especially in patients with advanced disease, warranting consideration of other parameters in addition to pharmacokinetic monitoring of IV busulfan to decrease VOD in high risk patient populations.

Hepatic veno-occlusive disease cases (n=4)

sex/agediseasestateAUCinfAUCssOutcomeComment
F/41 CML blast crisis 511.0 539.7 death unrelated donor 
F/49 CML chronic phase 739.4 991.0 recovered  
F/39 ALL 2nd CR 1472.1 1465.6 recovered 
M/17 ALL 2nd relapse 1302.7 1560.8 death pseudomonas sepsis 
sex/agediseasestateAUCinfAUCssOutcomeComment
F/41 CML blast crisis 511.0 539.7 death unrelated donor 
F/49 CML chronic phase 739.4 991.0 recovered  
F/39 ALL 2nd CR 1472.1 1465.6 recovered 
M/17 ALL 2nd relapse 1302.7 1560.8 death pseudomonas sepsis 

Disclosure: No relevant conflicts of interest to declare.

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