Target dose adjustment of busulfan in pediatric patients undergoing bone marrow transplantation.
Published data suggest that the average concentration of busulfan at steady state (Bu Css) is critical for successful engraftment in children receiving busulfan as a conditioning agent for bone marrow transplantation (BMT). We previously found in children that a Bu Css <600 ng/ml correlated with autologous recovery/mixed chimerism; there was no correlation between Bu Css and regimen-related toxicity (RRT). In a cohort continuous with the previous trial, we prospectively evaluated targeted busulfan concentrations in 32 pediatric patients (age 0.6-18.5 years) with AML (n = 6), CML (n = 6) and non-malignant disorders (n = 20) receiving HLA-closely matched donor grafts. In this trial, individual busulfan pharmacokinetics were performed prior to admission. Busulfan doses were then adjusted to achieve a Bu Css target range of 600-900 ng/ml +/- 10% depending on donor source and disease. A repeat study was done following dose 1 of the conditioning regimen. Thirty of thirty-two (94%) patients achieved target concentrations. Total busulfan doses ranged from 10.9 to 29 mg/kg. Thirty of thirty-two patients (94%) have durably engrafted. Grade 3/4 RRT occurred in seven patients (21%). Targeting Bu Css ranges of 600-900 ng/ml significantly improved our rate of successful engraftment from 74% to 94% (P = 0.043). These results indicate that targeted busulfan dosing optimizes allogeneic engraftment in children.
Bolinger
A M
AM
University of California at San Francisco, Department of Clinical Pharmacy, San Francisco, CA 94143-0622, USA.
Zangwill
A B
AB
Slattery
J T
JT
Risler
L J
LJ
Sultan
D H
DH
Glidden
D V
DV
Norstad
D
D
Cowan
M J
MJ
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000706:statistics & numerical data; D002066:Busulfan / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004334:Drug Administration Schedule; D006084:Graft Rejection / Q000175:diagnosis; D006801:Humans; D007223:Infant; D011446:Prospective Studies; D019172:Transplantation Conditioning / Q000379:methods* / Q000706:statistics & numerical data
D002066:Busulfan