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Treosulfan-based conditioning for inborn errors of immunity

Inborn errors of immunity (IEI) are inherited disorders that lead to defects in the development and/or function of the immune system. The number of disorders that can be treated by haematopoietic stem-cell transplantation (HSCT) has increased rapidly with the advent of next-generation sequencing. Th...

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Autores principales: Slatter, Mary A., Gennery, Andrew R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141989/
https://www.ncbi.nlm.nih.gov/pubmed/34094045
http://dx.doi.org/10.1177/20406207211013985
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author Slatter, Mary A.
Gennery, Andrew R.
author_facet Slatter, Mary A.
Gennery, Andrew R.
author_sort Slatter, Mary A.
collection PubMed
description Inborn errors of immunity (IEI) are inherited disorders that lead to defects in the development and/or function of the immune system. The number of disorders that can be treated by haematopoietic stem-cell transplantation (HSCT) has increased rapidly with the advent of next-generation sequencing. The methods used to transplant children with IEI have improved dramatically over the last 20 years. The introduction of reduced-toxicity conditioning is an important factor in the improved outcome of HSCT. Treosulfan has myeloablative and immunosuppressive properties, enabling engraftment with less toxicity than traditionally used doses of busulfan. It is firmly incorporated into the conditioning guidelines of the Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation. Unlike busulfan, pharmacokinetically guided dosing of treosulfan is not part of routine practice, but data are emerging which indicate that further improvements in outcome may be possible, particularly in infants who have a decreased clearance of treosulfan. It is likely that individualized dosing, not just of treosulfan, but of all agents used in conditioning regimens, will be developed and implemented in the future. This will lead to a reduction in unwanted variability in drug exposure, leading to more predictable and adjustable exposure, and improved outcome of HSCT, with fewer late adverse effects and improved quality of life. Such conditioning regimens can be used as the basis to study the need for additional agents in certain disorders which are difficult to engraft or require high levels of donor chimerism, the dosing of individual cellular components within grafts, and effects of adjuvant cellular or immunotherapy post-transplant. This review documents the establishment of treosulfan worldwide, as a safe and effective agent for conditioning children with IEI prior to HSCT.
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spelling pubmed-81419892021-06-04 Treosulfan-based conditioning for inborn errors of immunity Slatter, Mary A. Gennery, Andrew R. Ther Adv Hematol Review Inborn errors of immunity (IEI) are inherited disorders that lead to defects in the development and/or function of the immune system. The number of disorders that can be treated by haematopoietic stem-cell transplantation (HSCT) has increased rapidly with the advent of next-generation sequencing. The methods used to transplant children with IEI have improved dramatically over the last 20 years. The introduction of reduced-toxicity conditioning is an important factor in the improved outcome of HSCT. Treosulfan has myeloablative and immunosuppressive properties, enabling engraftment with less toxicity than traditionally used doses of busulfan. It is firmly incorporated into the conditioning guidelines of the Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation. Unlike busulfan, pharmacokinetically guided dosing of treosulfan is not part of routine practice, but data are emerging which indicate that further improvements in outcome may be possible, particularly in infants who have a decreased clearance of treosulfan. It is likely that individualized dosing, not just of treosulfan, but of all agents used in conditioning regimens, will be developed and implemented in the future. This will lead to a reduction in unwanted variability in drug exposure, leading to more predictable and adjustable exposure, and improved outcome of HSCT, with fewer late adverse effects and improved quality of life. Such conditioning regimens can be used as the basis to study the need for additional agents in certain disorders which are difficult to engraft or require high levels of donor chimerism, the dosing of individual cellular components within grafts, and effects of adjuvant cellular or immunotherapy post-transplant. This review documents the establishment of treosulfan worldwide, as a safe and effective agent for conditioning children with IEI prior to HSCT. SAGE Publications 2021-05-20 /pmc/articles/PMC8141989/ /pubmed/34094045 http://dx.doi.org/10.1177/20406207211013985 Text en © The Author(s), 2021 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Review
Slatter, Mary A.
Gennery, Andrew R.
Treosulfan-based conditioning for inborn errors of immunity
title Treosulfan-based conditioning for inborn errors of immunity
title_full Treosulfan-based conditioning for inborn errors of immunity
title_fullStr Treosulfan-based conditioning for inborn errors of immunity
title_full_unstemmed Treosulfan-based conditioning for inborn errors of immunity
title_short Treosulfan-based conditioning for inborn errors of immunity
title_sort treosulfan-based conditioning for inborn errors of immunity
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141989/
https://www.ncbi.nlm.nih.gov/pubmed/34094045
http://dx.doi.org/10.1177/20406207211013985
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