Unpredictability of Intravenous Busulfan Pharmacokinetics in Children Undergoing Hematopoietic Stem Cell Transplantation for Advanced Beta Thalassemia: Limited Toxicity with a Dose-Adjustment Policy

Robert Chiesa, Barbara Cappelli, Roberto Crocchiolo, Ilaria Frugnoli, Erika Biral, Anna Noè, Costanza Evangelio, Marco Fossati, Tito Roccia, Alessandra Biffi, Valentina Finizio, Alessandro Aiuti, Monica Broglia, Antonella Bartoli, Fabio Ciceri, Maria Grazia Roncarolo, Sarah Marktel

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)622-628
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume16
Issue number5
DOIs
Publication statusPublished - May 2010

Keywords

  • Conditioning regimen
  • Hemoglobinopathies
  • Regimen-related toxicity

ASJC Scopus subject areas

  • Transplantation
  • Hematology

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