Individual dose adjustment of oral busulfan using a test dose in hematopoietic stem cell transplantation.
Maintaining the appropriate average steady-state plasma concentrations (Css) of busulfan (BU) is critical for both successful engraftment and minimizing toxicity in hematopoietic stem cell transplantation (HST). We therefore performed a prospective trial with 50 adult Japanese patients that involved adjusting the BU dose in accordance with individual BU pharmacokinetics (PK). After administering a 0.5-mg/kg test dose of oral BU, we analyzed individual BU PK parameters and calculated an adjusted BU dose that would achieve a target BU Css of 850 ng/mL. Thirty-nine patients (78%) required a BU dose decrease, and the median adjusted BU dose was 0.81 mg/kg (range, 0.51-1.29 mg/kg). All patients who underwent allogeneic HST received the adjusted BU dose. After administering the sixth BU dose, we measured the plasma BU concentration. The actual BU concentration was significantly correlated with the expected BU concentration, and the predictability of the BU Css was 103% +/- 9%. The incidence of toxicity excluding oral mucositis was low, and there was no regimen-related toxicity-associated mortality. Engraftment was achieved in 98% of the patients. This study showed that our method for adjusting the BU dose facilitated reliable prediction of the actual BU Css and that individualized BU dose adjustment was able to improve clinical outcomes in HST recipients treated with a BU-containing conditioning regimen.
Takamatsu
Yasushi
Y
First Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. yasushi@fukuoka-u.ac.jp
Sasaki
Noriaki
N
Eto
Tetsuya
T
Nagafuji
Koji
K
Abe
Yasunobu
Y
Choi
Ilseung
I
Ogata
Kentaro
K
Hara
Shuuji
S
Suzumiya
Junji
J
Tamura
Kazuo
K
D000284:Administration, Oral; D000328:Adult; D044466:Asian People; D002066:Busulfan / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000009:adverse effects / Q000493:pharmacokinetics*; D011446:Prospective Studies; D013280:Stomatitis / Q000139:chemically induced; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D019653:Myeloablative Agonists; D002066:Busulfan