Optimizing drug therapy in pediatric SCT: Focus on pharmacokinetics

J. S. McCune, P. Jacobson, A. Wiseman, O. Militano

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations

Abstract

Given age-related differences in drug metabolism and indications for hematopoietic SCT (HSCT), personalized drug dosing of the conditioning regimen and post-transplant immunosuppression may reduce graft rejection, relapse rates and toxicity in pediatric HSCT recipients. This manuscript summarizes the pharmacokinetic/dynamic data of HSCT conditioning and post-grafting immunosuppression, presented at the First Annual Pediatric Bone Marrow Transplant Consortium (PBMTC) meeting in April 2013. Personalized dosing of BU to a target plasma exposure reduces graft rejection in children and improves relapse/toxicity rates in adults. Current weight-based dosing achieves the target BU exposure in only a minority (24.3%) of children. The initial BU dose should be based on the European Medicines Agency nomogram or population pharmacokinetic models to improve the numbers of children achieving the target exposure. There are limited pharmacokinetic data for treosulfan, CY, fludarabine and alemtuzumab as HSCT conditioning in children. For post-grafting immunosuppression, mycophenolic acid (MPA) clearance may be increased in younger children (<12 years). The preferred MPA pharmacokinetic monitoring parameters and target range are still evolving in HSCT recipients. Multi-institutional trials incorporating properly powered pharmacokinetic/dynamic studies are needed to assess the effect of variability in the plasma exposure of drugs/metabolites on clinical outcomes in pediatric HSCT recipients.

Original languageEnglish (US)
Pages (from-to)165-172
Number of pages8
JournalBone marrow transplantation
Volume50
Issue number2
DOIs
StatePublished - Feb 7 2015

Bibliographical note

Funding Information:
Dr McCune has received research funding from Otsuka Pharmaceutical of North America. All other authors declare no conflict of interest.

Publisher Copyright:
© 2015 Macmillan Publishers Limited All rights reserved.

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