To see if the AUC of IV Bu was correlated to adverse effects, Andersson and colleagues treated 36 chronic myelogenous leukemia (CML) patients with either fixed or adjusted dose BuCy. The first 25 patients were given a fixed dose of Bu 0.8mg/kg every 6 hours. In the subsequent 12 patients, doses were adjusted to achieve an AUC of 1250uM-min (24h DIE 5000uM-min). At steady state, the population median AUC was 1265uM-min (range, 816-1905uM-min [24h DIE 5056uM-min; 3264-7620uM-min]). They found that the probabilities of developing gastrointestinal toxicity, hepatotoxicity, mucositis, and acute GVHD all increased with increasing AUC. The 26 patients within AUC of 950 - 1520uM-min (24h DIE 3800-6080uM-min) had a decreased incidence of death compared with the 10 patients outside this range. There were no cases of hepatic veno-occlusive disease or seizures. These were small numbers but did indicate a trend towards achieving an optimal systemic exposure by delivering individualized doses and a suggestion of a "therapeutic window" for Bu in this setting. The importance of being able to target BU exposure has been illustrated in the above discussion of reports correlating Bu pharmacokinetic parameters with its toxicity and efficacy. Thus, by utilizing a once daily IV dose, targeted to prespecified levels, Bu therapy can be optimized to limit toxicity and maximize efficacy.