TY - JOUR
T1 - Once-Daily Intravenous Busulfan with Therapeutic Drug Monitoring Compared to Conventional Oral Busulfan Improves Survival and Engraftment in Children Undergoing Allogeneic Stem Cell Transplantation
AU - Bartelink, Imke H.
AU - Bredius, Robbert G.M.
AU - Ververs, Tessa T.
AU - Raphael, Martine F.
AU - van Kesteren, Charlotte
AU - Bierings, Marc
AU - Rademaker, Carin M.A.
AU - den Hartigh, J.
AU - Uiterwaal, Cuno S.P.M.
AU - Zwaveling, Juliette
AU - Boelens, Jaap J.
N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/1
Y1 - 2008/1
N2 - Because of intra- and interindividual variability, bioavailability, and pharmacokinetics of busulfan (Bu) in children, oral busulfan without therapeutic drug monitoring (TDM) is assumed to be associated with higher graft failure rates as well as higher toxicity (eg, veno-occlusive disease [VOD]). This study compares the outcome of hematopoietic stem cell transplantation (HSCT) of 2 groups: 1) 30 patients who received myeloablation with once-daily intravenous (i.v.) dose-targeted busulfan (BUdtIV) based on TDM and 2) 30 patients who received the current practice of untargeted oral busulfan (BUPO). Patients received a 3-hour infusion of Bu at a first dose of 120 mg/m2 (age ≥1 year) or 80 mg/m2 (<1 year), or BUPO 1 mg/kg 4 times daily. Both regimens were continued for 4 days. The target area under the curve (AUC) was defined as 17,500 μg*h/l. BUdtIV resulted in higher event-free survival (EFS) and survival rates compared to BUPO (EFS: 30% versus 83%, P < .001, survival: 53% versus 83%, P = .016). BUdtIV was associated with more cases of VOD. TDM was feasible in routine clinical practice. The results show that i.v. Bu using TDM is preferable over oral Bu in children undergoing allogeneic stem cell transplantation, especially in those at high risk for graft failure/relapse.
AB - Because of intra- and interindividual variability, bioavailability, and pharmacokinetics of busulfan (Bu) in children, oral busulfan without therapeutic drug monitoring (TDM) is assumed to be associated with higher graft failure rates as well as higher toxicity (eg, veno-occlusive disease [VOD]). This study compares the outcome of hematopoietic stem cell transplantation (HSCT) of 2 groups: 1) 30 patients who received myeloablation with once-daily intravenous (i.v.) dose-targeted busulfan (BUdtIV) based on TDM and 2) 30 patients who received the current practice of untargeted oral busulfan (BUPO). Patients received a 3-hour infusion of Bu at a first dose of 120 mg/m2 (age ≥1 year) or 80 mg/m2 (<1 year), or BUPO 1 mg/kg 4 times daily. Both regimens were continued for 4 days. The target area under the curve (AUC) was defined as 17,500 μg*h/l. BUdtIV resulted in higher event-free survival (EFS) and survival rates compared to BUPO (EFS: 30% versus 83%, P < .001, survival: 53% versus 83%, P = .016). BUdtIV was associated with more cases of VOD. TDM was feasible in routine clinical practice. The results show that i.v. Bu using TDM is preferable over oral Bu in children undergoing allogeneic stem cell transplantation, especially in those at high risk for graft failure/relapse.
KW - Administration, Oral
KW - Adolescent
KW - Age Factors
KW - Allogeneic stem cell transplantation
KW - Busulfan
KW - Busulfan/administration & dosage
KW - Child
KW - Child, Preschool
KW - Disease-Free Survival
KW - Dose-Response Relationship, Drug
KW - Drug Monitoring
KW - Female
KW - Hematopoietic Stem Cell Transplantation/methods
KW - Humans
KW - Infant
KW - Infusions, Intravenous
KW - Male
KW - Myeloablative Agonists/administration & dosage
KW - Therapeutic drug monitoring
KW - Transplantation Conditioning/methods
KW - Transplantation, Homologous
UR - http://www.scopus.com/inward/record.url?scp=37349060017&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bbmt.2007.09.015
DO - https://doi.org/10.1016/j.bbmt.2007.09.015
M3 - Article
C2 - 18158965
SN - 1083-8791
VL - 14
SP - 88
EP - 98
JO - Biology of blood and marrow transplantation
JF - Biology of blood and marrow transplantation
IS - 1
ER -