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Improved outcome of HSCT in STAT1 gain-of-function disease following JAK inhibition bridging

Title: Improved outcome of HSCT in STAT1 gain-of-function disease following JAK inhibition bridging
Authors: Buddingh, Emilie Pauline; Slatter, Mary; Aldave Becerra, Juan Carlos; Alonso Garcia, Laura; Asmuth, Erik von; Baris, Safa; Calle-Martín, Oscar de la; Chan, Alice Y.; Chan, Su-Wan Bianca; Chandrakasan, Shanmuganathan; Chellapandian, Deepakbabu; Dara, Jasmeen; Farmand, Susan; Fasth, Anders; Satter, Lisa Forbes; Formankova, Renata; Grunebaum, Eyal; Keogh, Steven J.; Kiykim, Ayça; Kühl, Jörn-Sven; Laberko, Alexandra; Leahy, Timothy Ronan; Lindemans, Caroline; Martinez, Caridad; Martínez-Martínez, Laura; Mitchell, William Glenn; Morris, Emma; Oved, Joseph H.; Polacik, Maria; Rivière, Jacques G.; Roifman, Chaim M.; Kilic, Sara Sebnem; Sedlacek, Petr; Shah, Ami J.; Vong, Linda; Lankester, Arjan C.; Albert, Michael H.; Neven, Bénédicte; Torgerson, Troy; Leiding, Jennifer; Schuetz, Catharina
Contributors: National Institutes of Health; National Institute of Allergy and Infectious Diseases; Office of Rare Diseases Research; National Center for Advancing Translational Sciences; Deutsche Forschungsgemeinschaft
Source: Journal of Human Immunity ; volume 1, issue 3 ; ISSN 3065-8993
Publisher Information: Rockefeller University Press
Publication Year: 2025
Description: 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.
Document Type: article in journal/newspaper
Language: English
DOI: 10.70962/jhi.20250027
DOI: 10.70962/jhi.20250027/1948050/jhi_20250027.pdf
Availability: https://doi.org/10.70962/jhi.20250027; https://rupress.org/jhi/article-pdf/doi/10.70962/jhi.20250027/1948050/jhi_20250027.pdf
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.DEF23A1B
Database: BASE