Improved outcome of HSCT in STAT1 gain-of-function disease following JAK inhibition bridging
Publication date
2025-09-01
Authors
Buddingh, Emilie Pauline
Slatter, Mary
Becerra, Juan Carlos Aldave
Garcia, Laura Alonso
von Asmuth, Erik
Baris, Safa
de la Calle-Martín, Oscar
Chan, Alice Y.
Chan, Su Wan Bianca
Chandrakasan, Shanmuganathan
Editors
Advisors
Supervisors
Document Type
Article
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Abstract
Germline gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) are associated with infections, including chronic mucocutaneous candidiasis and autoimmunity. Morbidity is high, and disease manifestations can be life-threatening. Curative allogeneic hematopoietic stem cell transplantation (HSCT) historically has had poor outcomes. We identified 36 patients with STAT1 GOF disease, receiving 40 HSCT procedures in 2010–2023, in a combined effort of the EBMT-IEWP and the PIDTC. Median age at first transplant was 11 years (range 1–33). Indications for HSCT were combined immunodeficiency, severe and/or refractory infections, and autoimmunity. Acute GvHD occurred in 22/40 HSCT procedures; 5 patients suffered from grade III/IV acute GvHD. One patient had chronic GvHD. Overall survival was 72.2%, and event-free survival was 55.6%, markedly improved from an earlier report on HSCT for STAT1 GOF disease. Patients with an HCT-CI score of 1 or higher had worse outcome. Pre-treatment with Janus kinase (JAK) inhibitors was associated with better event-free survival.
Keywords
Inborn errors of immunity, Severe immunodeficiencies, Therapeutics, Immunology, Immunology and Allergy, Genetics(clinical)
Citation
Buddingh, E P, Slatter, M, Becerra, J C A, Garcia, L A, von Asmuth, E, Baris, S, de la Calle-Martín, O, Chan, A Y, Chan, S W B, Chandrakasan, S, Chellapandian, D, Dara, J, Farmand, S, Fasth, A, Satter, L F, Formankova, R, Grunebaum, E, Keogh, S J, Kiykim, A, Kühl, J S, Laberko, A, Leahy, T R, Lindemans, C, Martinez, C, Martínez-Martínez, L, Mitchell, W G, Morris, E, Oved, J H, Polacik, M, Rivière, J G, Roifman, C M, Kilic, S S, Sedlacek, P, Shah, A J, Vong, L, Lankester, A C, Albert, M H, Neven, B, Torgerson, T, Leiding, J, Schuetz, C & Inborn Errors Working Party (IEWP), European Society for Blood and Marrow Transplantation (EBMT) and Primary Immunodeficiency Treatment Consortium (PIDTC) 2025, 'Improved outcome of HSCT in STAT1 gain-of-function disease following JAK inhibition bridging', Journal of human immunity, vol. 1, no. 3, e20250027. https://doi.org/10.70962/jhi.20250027