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Lookup NU author(s): Sinéad Greener, Dr Zohreh Nademi, Dr Stephen Owens, Dr Khuen Foong Ng, Dr Terence Flood, Professor Andrew GenneryORCiD, Professor Sophie HambletonORCiD, Professor Mary Slatter
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.Allogeneic haematopoietic stem cell transplantation (HSCT) is a curative therapy for severe combined immunodeficiency (SCID). Conditioning improves donor engraftment and freedom from immunoglobulin replacement (IgR) but increases the risks of acute and late toxicity. Treosulfan, a reduced toxicity alkylating agent, has emerged as an alternative to busulfan. In this UK multicentre study, we evaluated outcomes of 104 infants with SCID who underwent first HSCT following treosulfan-fludarabine conditioning between 2006 and 2022. After a median follow-up of 5.4 years, 5-year overall survival (OS) and event-free survivals (EFS) were 81% and 77% respectively. On multivariate analysis, molecularly undefined SCID (OS hazard ratio [HR] 5.61; EFS HR 5.55) and pre-HSCT cytomegalovirus (CMV) infection (OS HR 3.94; EFS 3.68) were independently associated with inferior OS and EFS; RAG-DCLRE1C genotypes also predicted worse EFS (HR 4.35). Cumulative incidence of endothelial cell dysfunction (ECD) was 11%. Treosulfan dose was not associated with OS, EFS, ECD or donor myeloid chimerism. Low mixed donor myeloid chimerism was observed across all treosulfan doses, but IgR freedom was achieved in 92% of survivors after first HSCT. Treosulfan-fludarabine provides excellent survival with low endothelial toxicity for SCID HSCT, with potential for optimisation via pharmacokinetic guided dosing.
Author(s): Lum SH, Greener S, Memon IL, Amrolia P, Nademi Z, Chiesa R, Silva J, Young H, Owens S, Williams E, Ng KF, Flood T, Gennery AR, Hambleton S, Rao K, Slatter M
Publication type: Article
Publication status: Published
Journal: British Journal of Haematology
Year: 2026
Pages: epub ahead of print
Online publication date: 10/04/2026
Acceptance date: 12/03/2026
Date deposited: 21/04/2026
ISSN (print): 0007-1048
ISSN (electronic): 1365-2141
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1111/bjh.70453
DOI: 10.1111/bjh.70453
Data Access Statement: The data that support the findings of this study are available from the corresponding author
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