TY - JOUR
T1 - Improved outcome of HSCT in STAT1 gain-of-function disease following JAK inhibition bridging
AU - Buddingh, Emilie Pauline
AU - Slatter, Mary
AU - Becerra, Juan Carlos Aldave
AU - Garcia, Laura Alonso
AU - von Asmuth, Erik
AU - Baris, Safa
AU - de la Calle-Martín, Oscar
AU - Chan, Alice Y.
AU - Chan, Su Wan Bianca
AU - Chandrakasan, Shanmuganathan
AU - Chellapandian, Deepakbabu
AU - Dara, Jasmeen
AU - Farmand, Susan
AU - Fasth, Anders
AU - Satter, Lisa Forbes
AU - Formankova, Renata
AU - Grunebaum, Eyal
AU - Keogh, Steven J.
AU - Kiykim, Ayça
AU - Kühl, Jörn Sven
AU - Laberko, Alexandra
AU - Leahy, Timothy Ronan
AU - Lindemans, Caroline
AU - Martinez, Carad
AU - Martínez-Martínez, Laura
AU - Mitchell, William Glenn
AU - Morris, Emma
AU - Oved, Joseph H.
AU - Polacik, Maria
AU - Rivière, Jacques G.
AU - Roifman, Chaim M.
AU - Kilic, Sara Sebnem
AU - Sedlacek, Petr
AU - Shah, Ami J.
AU - Vong, Linda
AU - Lankester, Arjan C.
AU - Albert, Michael H.
AU - Neven, Bénédicte
AU - Torgerson, Troy
AU - Leiding, Jennifer
AU - Schuetz, Catharina
N1 - Publisher Copyright:
© 2025 Buddingh et al.
PY - 2025/9/1
Y1 - 2025/9/1
N2 - 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.
AB - 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.
KW - Inborn errors of immunity
KW - Severe immunodeficiencies
KW - Therapeutics
UR - https://www.scopus.com/pages/publications/105039313502
U2 - 10.70962/jhi.20250027
DO - 10.70962/jhi.20250027
M3 - Article
AN - SCOPUS:105039313502
SN - 3065-8993
VL - 1
JO - Journal of human immunity
JF - Journal of human immunity
IS - 3
M1 - e20250027
ER -