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

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. · Journal of Human Immunity (2025) · DOI: 10.70962/jhi.20250027

Resumen

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.