Browse by author
Lookup NU author(s): Professor Mary Slatter, Professor Andrew GenneryORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© The Author(s), 2021.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.
Author(s): Slatter MA, Gennery AR
Publication type: Review
Publication status: Published
Journal: Therapeutic Advances in Hematology
Year: 2021
Volume: 12
Pages: 1-19
Online publication date: 20/05/2021
Acceptance date: 12/04/2021
ISSN (print): 2040-6207
ISSN (electronic): 2040-6215
Publisher: SAGE Publications Ltd
URL: https://doi.org/10.1177/20406207211013985
DOI: 10.1177/20406207211013985
