Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2025 Aug 26;9(16):4126-4135.
doi: 10.1182/bloodadvances.2025016158.

Allogeneic hematopoietic stem cell transplantation for STAT3 hyper-IgE syndrome: a worldwide study

Christo Tsilifis  1   2 , Johannes Raedler  3 , Joanna Renke  4   5 , Michael Medinger  6 , Alexandra Laberko  7 , Ásgeir Haraldsson  8 , Niraj Patel  9 , Peter Ciznar  10 , Melanie Wong  11 , Steven J Keogh  12 , Paul Gray  13   14 , Richard Mitchell  15   16 , Venetia Bigley  2   17 , Suzanne Elcombe  18 , Fabian Hauck  3 , Michael H Albert  3 , Eleni Tholouli  19 , Archana Herwadkar  20 , Shuayb Elkhalifa  21   22 , Chris Kosmidis  23 , Giorgio Callisti  24 , Lauri M Burroughs  25 , Karin Chen  26 , Ben Carpenter  27   28 , Thomas A Fox  27   28 , Emma C Morris  27   28   29 , Ramya Uppuluri  30 , Revathi Raj  30 , Masakatsu Yanagimachi  31   32 , Emilie P Buddingh  33 , Christina Oikonomopoulou  34 , Corina Gonzalez  35 , Dimana Dimitrova  36 , Jennifer A Kanakry  36 , Danielle Arnold  35 , Sung-Yun Pai  35 , Mary A Slatter  1   2 , Mark S Pearce  37 , Austen Worth  38 , Alexandra F Freeman  39 , Andrew R Gennery  1   2
Affiliations
Multicenter Study

Allogeneic hematopoietic stem cell transplantation for STAT3 hyper-IgE syndrome: a worldwide study

Christo Tsilifis et al. Blood Adv. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
OS at 5 years for all patients.
Figure 2.
Figure 2.
EFS at 5 years for all patients. Events were defined as graft failure, chronic GVHD of any grade, and death.
Figure 3.
Figure 3.
Donor chimerism kinetics by conditioning regimen, and comparison of serum IgE. (A) Latest donor chimerism by cell line for surviving patients stratified by conditioning regimen backbone. (B) Comparison of pre-HSCT and post-HSCT serum IgE (kU/L) by Wilcoxon matched-pairs signed rank test. (C) Latest donor chimerism by cell line for surviving patients. Horizontal line represents median. (D) Proportion of patients with full (>90%) vs mixed chimerism by conditioning regimen backbone. (E) Proportion of patients with full (>90%) vs mixed chimerism by age at HSCT. Bu, busulfan; Mel, melphalan; Treo, treosulfan.
See this image and copyright information in PMC

References

    1. Holland SM, DeLeo FR, Elloumi HZ, et al. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007;357(16):1608–1619. - PubMed
    1. Minegishi Y, Saito M, Tsuchiya S, et al. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature. 2007;448(7157):1058–1062. - PubMed
    1. Gernez Y, Freeman AF, Holland SM, et al. Autosomal dominant hyper-IgE syndrome in the USIDNET Registry. J Allergy Clin Immunol Pract. 2018;6(3):996–1001. - PMC - PubMed
    1. Renner ED, Puck JM, Holland SM, et al. Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity. J Pediatr. 2004;144(1):93–99. - PubMed
    1. Chandesris M-O, Melki I, Natividad A, et al. Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey. Medicine (Baltimore) 2012;91(4):e1–e19. - PMC - PubMed

Publication types

MeSH terms

Substances