TY - JOUR
T1 - Unpredictability of Intravenous Busulfan Pharmacokinetics in Children Undergoing Hematopoietic Stem Cell Transplantation for Advanced Beta Thalassemia
T2 - Limited Toxicity with a Dose-Adjustment Policy
AU - Chiesa, Robert
AU - Cappelli, Barbara
AU - Crocchiolo, Roberto
AU - Frugnoli, Ilaria
AU - Biral, Erika
AU - Noè, Anna
AU - Evangelio, Costanza
AU - Fossati, Marco
AU - Roccia, Tito
AU - Biffi, Alessandra
AU - Finizio, Valentina
AU - Aiuti, Alessandro
AU - Broglia, Monica
AU - Bartoli, Antonella
AU - Ciceri, Fabio
AU - Roncarolo, Maria Grazia
AU - Marktel, Sarah
PY - 2010/5
Y1 - 2010/5
N2 - β-thalassemia is a major health problem worldwide, and stem cell transplantation (SCT) is the only curative option. Oral Busulfan (Bu) based conditioning is widely used in this setting. Due to the variability of Bu systemic exposure, intravenous (i.v.) Bu has been proposed as a standard of care, with no need for drug monitoring and dose adjustment. Patients with β-thalassemia from countries with limited resources might be at higher risk of erratic Bu metabolism because of liver dysfunction, severe iron overload, and specific ethnic/genetic features. We studied Bu pharmacokinetics in 53 children with advanced β-thalassemia from Middle Eastern countries who underwent a total of 57 matched related donor SCTs. Forty-two percent of the children required dose adjustment because they did not achieve the therapeutic window after the first dose. With a Bu dose-adjustment policy, regimen-related toxicity was limited. At a median follow-up of 564 days, the probabilities of 2-year survival, current thalassemia-free survival, rejection, and treatment-related mortality were 96%, 88%, 21%, and 4%, respectively. Conditioning with i.v. Bu and dose adjustment is feasible and well tolerated, although recurrence of thalassemia remains an unsolved problem in children with advanced disease.
AB - β-thalassemia is a major health problem worldwide, and stem cell transplantation (SCT) is the only curative option. Oral Busulfan (Bu) based conditioning is widely used in this setting. Due to the variability of Bu systemic exposure, intravenous (i.v.) Bu has been proposed as a standard of care, with no need for drug monitoring and dose adjustment. Patients with β-thalassemia from countries with limited resources might be at higher risk of erratic Bu metabolism because of liver dysfunction, severe iron overload, and specific ethnic/genetic features. We studied Bu pharmacokinetics in 53 children with advanced β-thalassemia from Middle Eastern countries who underwent a total of 57 matched related donor SCTs. Forty-two percent of the children required dose adjustment because they did not achieve the therapeutic window after the first dose. With a Bu dose-adjustment policy, regimen-related toxicity was limited. At a median follow-up of 564 days, the probabilities of 2-year survival, current thalassemia-free survival, rejection, and treatment-related mortality were 96%, 88%, 21%, and 4%, respectively. Conditioning with i.v. Bu and dose adjustment is feasible and well tolerated, although recurrence of thalassemia remains an unsolved problem in children with advanced disease.
KW - Conditioning regimen
KW - Hemoglobinopathies
KW - Regimen-related toxicity
UR - http://www.scopus.com/inward/record.url?scp=77951207835&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951207835&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2009.11.024
DO - 10.1016/j.bbmt.2009.11.024
M3 - Article
C2 - 19963071
AN - SCOPUS:77951207835
VL - 16
SP - 622
EP - 628
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 5
ER -