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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Emilie Pauline Buddingh - , Leiden University Medical Centre (LUMC) (Author)
  • Mary Slatter - , Newcastle upon Tyne Hospitals NHS Foundation Trust (Author)
  • Juan Carlos Aldave Becerra - , Hospital Nacional Edgardo Rebagliati Martins (Author)
  • Laura Alonso Garcia - , Vall d'Hebron Research Institute (VHIR) (Author)
  • Erik von Asmuth - , Leiden University Medical Centre (LUMC) (Author)
  • Safa Baris - , Marmara University (Author)
  • Oscar de la Calle-Martín - , Autonomous University of Barcelona (Author)
  • Alice Y Chan - , University of California at San Francisco (Author)
  • Su-Wan Bianca Chan - , KK Women's and Children's Hospital (Author)
  • Shanmuganathan Chandrakasan - , Children's Healthcare of Atlanta (Author)
  • Deepakbabu Chellapandian - , Johns Hopkins All Children's Hospital (Author)
  • Jasmeen Dara - , University of California at San Francisco (Author)
  • Susan Farmand - , University Hospital Hamburg Eppendorf (Author)
  • Anders Fasth - , University of Gothenburg (Author)
  • Lisa Forbes Satter - , Texas Children's Hospital Houston (Author)
  • Renata Formankova - , University Hospital Motol (Author)
  • Eyal Grunebaum - , Hospital for Sick Children (Author)
  • Steven J Keogh - , The Children's Hospital at Westmead (Author)
  • Ayça Kiykim - , Istanbul University Cerrahpaşa (Author)
  • Jörn-Sven Kühl - , University Hospital Leipzig (Author)
  • Alexandra Laberko - , Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology (Author)
  • Timothy Ronan Leahy - , Children’s Health Ireland at Crumlin (Author)
  • Caroline Lindemans - , University Medical Center (UMC) Utrecht (Author)
  • Caridad Martinez - , Texas Children's Hospital Houston (Author)
  • Laura Martínez-Martínez - , Hospital de la Santa creu i Sant Pau, Autonomous University of Barcelona (Author)
  • William Glenn Mitchell - , Children's Healthcare of Atlanta (Author)
  • Emma Morris - , University College London (Author)
  • Joseph H Oved - , Memorial Sloan-Kettering Cancer Center (Author)
  • Maria Polacik - , Department of Paediatrics, University Center for Rare Diseases (Author)
  • Jacques G Rivière - , Vall d'Hebron Research Institute (VHIR) (Author)
  • Chaim M Roifman - , Hospital for Sick Children (Author)
  • Sara Sebnem Kilic - , Bursa Uludağ University (Author)
  • Petr Sedlacek - , University Hospital Motol (Author)
  • Ami J Shah - , Stanford University (Author)
  • Linda Vong - , Hospital for Sick Children (Author)
  • Arjan C Lankester - , Leiden University Medical Centre (LUMC) (Author)
  • Michael H Albert - , Haunersches Kinderspital in Munich (Author)
  • Bénédicte Neven - , INSERM - Institut national de la santé et de la recherche médicale, Necker–Enfants Malades Hospital (Author)
  • Troy Torgerson - , Allen Institute for Immunology (Author)
  • Jennifer Leiding - , Johns Hopkins All Children's Hospital (Author)
  • Catharina Schuetz - , Department of Paediatrics, German Center for Child and Adolescent Health (DZKJ) - Partner Site Leipzig/Dresden, University Center for Rare Diseases (Author)

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.

Details

Original languageEnglish
Article numbere20250027
JournalJournal of human immunity
Volume1
Issue number3
Publication statusPublished - 1 Sept 2025
Peer-reviewedYes

External IDs

PubMedCentral PMC12551681
ORCID /0009-0003-6519-0482/work/196687562
unpaywall 10.70962/jhi.20250027