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Optimizing drug therapy in pediatric SCT: Focus on pharmacokinetics

Bone Marrow Transplantation volume 50, pages 165–172 (2015)Cite this article

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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.

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Acknowledgements

This work was supported by grants from the NCI (#1R13CA177155-01, 1R01CA182963, 1R21162059), NHLBI (#5U10HL069254-13), Pediatric Cancer Research Foundation, Children’s Cancer Fund, NMDP Foundation and St Baldrick’s Foundation.

Author information

Authors and Affiliations

  1. University of Washington School of Pharmacy and Fred Hutchinson Cancer Research Center, Seattle, WA, USA,

    J S McCune

  2. Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA,

    P Jacobson

  3. School of Medicine, University of Minnesota, Minneapolis, MN, USA

    A Wiseman

  4. Maria Fareri Children’s Hospital at Westchester Medical Center, New York Medical College, Valhalla, NY, USA

    O Militano

Authors
  1. J S McCune
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  2. P Jacobson
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  3. A Wiseman
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  4. O Militano
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Corresponding author

Correspondence to O Militano.

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Competing interests

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

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McCune, J., Jacobson, P., Wiseman, A. et al. Optimizing drug therapy in pediatric SCT: Focus on pharmacokinetics. Bone Marrow Transplant 50, 165–172 (2015). https://doi.org/10.1038/bmt.2014.235

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