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Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial
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 leas...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484914/ https://www.ncbi.nlm.nih.gov/pubmed/31701524 http://dx.doi.org/10.1002/cpt.1715 |
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author | Chiesa, Robert Standing, Joseph F. Winter, Robert Nademi, Zohreh Chu, Jan Pinner, Danielle Kloprogge, Frank McLellen, Susan Amrolia, Persis J. Rao, Kanchan Lucchini, Giovanna Silva, Juliana Ciocarlie, Oana Lazareva, Arina Gennery, Andrew R. Doncheva, Bilyana Cant, Andrew J. Hambleton, Sophie Flood, Terence Rogerson, Elizabeth Devine, Kirsty Prunty, Helen Heales, Simon Veys, Paul Slatter, Mary |
author_facet | Chiesa, Robert Standing, Joseph F. Winter, Robert Nademi, Zohreh Chu, Jan Pinner, Danielle Kloprogge, Frank McLellen, Susan Amrolia, Persis J. Rao, Kanchan Lucchini, Giovanna Silva, Juliana Ciocarlie, Oana Lazareva, Arina Gennery, Andrew R. Doncheva, Bilyana Cant, Andrew J. Hambleton, Sophie Flood, Terence Rogerson, Elizabeth Devine, Kirsty Prunty, Helen Heales, Simon Veys, Paul Slatter, Mary |
author_sort | Chiesa, Robert |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7484914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74849142020-09-18 Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial Chiesa, Robert Standing, Joseph F. Winter, Robert Nademi, Zohreh Chu, Jan Pinner, Danielle Kloprogge, Frank McLellen, Susan Amrolia, Persis J. Rao, Kanchan Lucchini, Giovanna Silva, Juliana Ciocarlie, Oana Lazareva, Arina Gennery, Andrew R. Doncheva, Bilyana Cant, Andrew J. Hambleton, Sophie Flood, Terence Rogerson, Elizabeth Devine, Kirsty Prunty, Helen Heales, Simon Veys, Paul Slatter, Mary Clin Pharmacol Ther Research 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. John Wiley and Sons Inc. 2019-12-14 2020-08 /pmc/articles/PMC7484914/ /pubmed/31701524 http://dx.doi.org/10.1002/cpt.1715 Text en © 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 terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Chiesa, Robert Standing, Joseph F. Winter, Robert Nademi, Zohreh Chu, Jan Pinner, Danielle Kloprogge, Frank McLellen, Susan Amrolia, Persis J. Rao, Kanchan Lucchini, Giovanna Silva, Juliana Ciocarlie, Oana Lazareva, Arina Gennery, Andrew R. Doncheva, Bilyana Cant, Andrew J. Hambleton, Sophie Flood, Terence Rogerson, Elizabeth Devine, Kirsty Prunty, Helen Heales, Simon Veys, Paul Slatter, Mary Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial |
title | Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial |
title_full | Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial |
title_fullStr | Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial |
title_full_unstemmed | Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial |
title_short | Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial |
title_sort | proposed therapeutic range of treosulfan in reduced toxicity pediatric allogeneic hematopoietic stem cell transplant conditioning: results from a prospective trial |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484914/ https://www.ncbi.nlm.nih.gov/pubmed/31701524 http://dx.doi.org/10.1002/cpt.1715 |
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