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Lookup NU author(s): Dr Christo TsilifisORCiD, Dr Venetia BigleyORCiD, Dr Suzanne Elcombe, Professor Mary Slatter, Professor Mark PearceORCiD, Professor Andrew GenneryORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2025 American Society of Hematology. All rights reserved. Signal transduction and activator of transcription 3 hyperimmunoglobulin E syndrome (STAT3-HIES) is a multisystem disorder causing recurrent skin and respiratory infection with bronchiectasis, pneumatoceles, and aspergillosis; lymphoma; and extraimmune manifestations including fractures and vasculopathy. Published data on immune and extraimmune hematopoietic stem cell transplant (HSCT) outcomes focus on case reports or small cohorts. We conducted an international multicenter retrospective study of HSCT in STAT3-HIES. Primary end points were overall survival (OS) and event-free survival (EFS; events were death, graft failure, chronic graft-versus-host disease [GVHD]). We identified 41 patients over a 28-year period. HSCT indication was infection (93%) or lymphoma (7%). Median age at HSCT was 14 years (range, 4-45). Most patients had pre-HSCT respiratory disease (93%), including parenchymal lung disease (68%), and prior suspected/confirmed pulmonary fungal infection (32%). Patients received peripheral blood stem cells (51%) or marrow (49%) from HLA 10/10-matched unrelated donors (44%), matched family donors (44%), mismatched family donors (10%), or 1 9/10-mismatched unrelated donor (2%). Conditioning regimens were predominantly treosulfan-based (59%; with thiotepa, 34%); other patients received busulfan-based (24%) or melphalan-based (17%) regimens. Median follow-up for surviving patients was 5 years (0.8-28). The 5-year OS was 93%, and 5-year EFS 90%. Cumulative incidence of grade 2 to 4 acute GVHD was 22%. Median whole blood donor chimerism at latest follow-up was 100%. Eighty-seven percent of patients have reduced or no bacterial or fungal respiratory infection. After HSCT, 20% developed new skeletal fractures. This worldwide study expanded data on HSCT for STAT3-HIES to 41 patients; despite significant pre-HSCT pulmonary morbidity, OS was high, and patients have improved skin and respiratory disease though the impact on extraimmune manifestations appears limited.
Author(s): Tsilifis C, Raedler J, Renke J, Medinger M, Laberko A, Haraldsson A, Patel N, Ciznar P, Wong M, Keogh SJ, Gray P, Mitchell R, Bigley V, Elcombe S, Hauck F, Albert MH, Tholouli E, Herwadkar A, Elkhalifa S, Kosmidis C, Callisti G, Burroughs LM, Chen K, Carpenter B, Fox TA, Morris EC, Uppuluri R, Raj R, Yanagimachi M, Buddingh EP, Oikonomopoulou C, Gonzalez C, Dimitrova D, Kanakry JA, Arnold D, Pai S-Y, Slatter MA, Pearce MS, Worth A, Freeman AF, Gennery AR
Publication type: Article
Publication status: Published
Journal: Blood Advances
Year: 2025
Volume: 9
Issue: 16
Pages: 4126-4135
Print publication date: 26/08/2025
Online publication date: 23/06/2025
Acceptance date: 02/05/2025
Date deposited: 16/09/2025
ISSN (print): 2473-9529
ISSN (electronic): 2473-9537
Publisher: American Society of Hematology
URL: https://doi.org/10.1182/bloodadvances.2025016158
DOI: 10.1182/bloodadvances.2025016158
Data Access Statement: The data used in this study are not publicly available, but deidentified data may be available upon reasonable request from the authors (Christo Tsilifis, email: c.tsilifis@ nhs.net).
PubMed id: 40540800
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