Modification of the Bu/Cy myeloablative regimen using daily parenteral busulfan: reduced toxicity without the need for pharmacokinetic monitoring.
Pharmacokinetic and clinical outcome measures among three groups of patients undergoing hematopoietic transplant were assessed: group A: Parenteral busulfan (Bu) 3.2 mg/kg i.v. given qd, n=20; group B: parenteral Bu 0.8 mg/kg i.v. given every 6 h, n=11; group C: Bu 1 mg/kg p.o. given every 6 h, n=25. All groups received Bu over 4 days followed by Cy 60 mg/kg i.v. qd over 2 days; followed by an infusion of allogeneic stem cells. Median Bu clearance was 3.21 ml/min/kg and median daily AUC was 4071 micromol/min for the group A patients. The dosing formula for Bu i.v. qd was highly predictive of the AUC for patients whose mass < or =IBW+20%. For patients of greater mass, the dosing formula uniformly resulted in lower-than-predicted AUC. Neurologic toxicity, hepatic toxicity, hematologic engraftment, and relapse at 100 days were comparable across all three groups. Severe AGVHD was least among group A, followed by group B when compared with group C. Bu i.v. qd is a safe and effective regimen for allogeneic transplantation and is at least clinically equivalent to every 6 h dosing schemes using either oral or parenteral Bu.
Mamlouk
K
K
Program in Blood and Marrow Transplantation, Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
Saracino
G
G
Berryman
R B
RB
Fay
J W
JW
Pineiro
L A
LA
Vance
E A
EA
White
M
M
Sandler
I
I
Agura
E D
ED
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D002066:Busulfan / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011874:Radiometry; D012189:Retrospective Studies; D013997:Time Factors; D019172:Transplantation Conditioning; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D002066:Busulfan