Chiesa, R;
Standing, JF;
Winter, R;
Nademi, Z;
Chu, J;
Pinner, D;
Kloprogge, F;
... Slatter, M; + view all
(2019)
Proposed therapeutic range of treosulfan in reduced toxicity pediatric allogeneic hematopoietic stem cell transplant conditioning: results from a prospective trial.
Clinical Pharmacology & Therapeutics
10.1002/cpt.1715.
(In press).
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Abstract
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.
Type: | Article |
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Title: | Proposed therapeutic range of treosulfan in reduced toxicity pediatric allogeneic hematopoietic stem cell transplant conditioning: results from a prospective trial |
Location: | United States |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1002/cpt.1715 |
Publisher version: | https://doi.org/10.1002/cpt.1715 |
Language: | English |
Additional information: | © 2019 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
URI: | https://discovery.ucl.ac.uk/id/eprint/10085747 |
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