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Lookup NU author(s): Dr Zohreh Nademi, Professor Andrew GenneryORCiD, Professor Andrew Cant, Professor Sophie Hambleton, Dr Terence Flood, Elizabeth Rogerson, Professor Mary Slatter
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.Treosulfan is given off-label in pediatric allogeneic hematopoietic stem cell transplant. This study investigated treosulfan's pharmacokinetics (PKs), efficacy, and safety in a prospective trial. Pediatric patients (n = 87) receiving treosulfan-fludarabine conditioning were followed for at least 1 year posttransplant. PKs were described with a two-compartment model. During follow-up, 11 of 87 patients died and 12 of 87 patients had low engraftment (≤ 20% myeloid chimerism). For each increase in treosulfan area under the curve from zero to infinity (AUC(0-∞)) of 1,000 mg hour/L the hazard ratio (95% confidence interval) for mortality increase was 1.46 (1.23–1.74), and the hazard ratio for low engraftment was 0.61 (0.36–1.04). A cumulative AUC(0-∞) of 4,800 mg hour/L maximized the probability of success (> 20% engraftment and no mortality) at 82%. Probability of success with AUC(0-∞) between 80% and 125% of this target were 78% and 79%. Measuring PK at the first dose and individualizing the third dose may be required in nonmalignant disease.
Author(s): Chiesa R, Standing JF, Winter R, Nademi Z, Chu J, Pinner D, Kloprogge F, McLellen S, Amrolia PJ, Rao K, Lucchini G, Silva J, Ciocarlie O, Lazareva A, Gennery AR, Doncheva B, Cant AJ, Hambleton S, Flood T, Rogerson E, Devine K, Prunty H, Heales S, Veys P, Slatter M
Publication type: Article
Publication status: Published
Journal: Clinical Pharmacology and Therapeutics
Year: 2019
Volume: 108
Issue: 2
Pages: 264-273
Print publication date: 01/08/2020
Online publication date: 07/11/2019
Acceptance date: 28/10/2019
Date deposited: 08/01/2020
ISSN (print): 0009-9236
ISSN (electronic): 1532-6535
Publisher: Nature Publishing Group
URL: https://doi.org/10.1002/cpt.1715
DOI: 10.1002/cpt.1715
PubMed id: 31701524
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