Randomized comparison of four-times-daily versus once-daily intravenous busulfan in conditioning therapy for hematopoietic cell transplantation.
Sixty patients were randomized to receive intravenous busulfan (iBU) either as 0.8 mg/kg, over 2 hours 4 times a day (BU4 arm) or 3.2 mg/kg, over 3 hours once a day (BU1 arm) in conditioning therapy for hematopoietic cell transplantation. The complete pharmacokinetic parameters for the first busulfan dose were obtained from all patients and were comparable between the 2 arms: for the BU4 and BU1 groups, elimination half-life (mean+/-SD) was 2.75+/-0.22 versus 2.83+/-0.21 hours, estimated daily AUC was 6058.0+/-1091.9 versus 6475.5+/-1099.4 microM.min per day, and clearance was 2.05+/-0.36 versus 1.91+/-0.31 mL/min/kg, respectively. Times to engraftment after transplantation were similar between the 2 arms. No significant differences were evident in the occurrence of acute graft-versus-host disease (aGVHD) and hepatic veno-occlusion disease (VOD). Moreover, other toxicities observed within 100 days after transplantation were not significantly different between the 2 arms. The cumulative incidence of nonrelapse mortality was 20.8% in BU4 arm and 13.3% in BU1 arm. In conclusion, our randomized study demonstrates that the pharmacokinetic profiles and posttransplant complications are similar for once-daily iBU and traditional 4-times-daily iBU.
Ryu
Seong-Gil
SG
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Lee
Je-Hwan
JH
Choi
Seong-Jun
SJ
Lee
Jung-Hee
JH
Lee
Young-Shin
YS
Seol
Miee
M
Hur
Eun-Hye
EH
Lee
Soo Han
SH
Bae
Kyun Seop
KS
Noh
Gyu Jeong
GJ
Lee
Moo-Song
MS
Yun
Sung-Cheol
SC
Han
Sang Beom
SB
Lee
Kyoo-Hyung
KH
D000293:Adolescent; D000328:Adult; D002066:Busulfan / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004334:Drug Administration Schedule; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006504:Hepatic Veno-Occlusive Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010599:Pharmacokinetics; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality
D002066:Busulfan