Allogeneic HSCT for Symptomatic Female X-linked Chronic Granulomatous Disease Carriers

Research output: Contribution to journalResearch articleContributedpeer-review


  • Christo Tsilifis - , Great North Children's Hospital, Newcastle University (Author)
  • Tuulia Torppa - , Newcastle University (Author)
  • Eleri J. Williams - , Great North Children's Hospital (Author)
  • Michael H. Albert - , Ludwig Maximilian University of Munich (Author)
  • Fabian Hauck - , Ludwig Maximilian University of Munich (Author)
  • Elena Soncini - , Brescia Civil Hospital (Author)
  • Elizabeth Kang - , National Institutes of Health (NIH) (Author)
  • Harry Malech - , National Institutes of Health (NIH) (Author)
  • Catharina Schuetz - , Department of Paediatrics (Author)
  • Horst von Bernuth - , Charité – Universitätsmedizin Berlin (Author)
  • Mary A. Slatter - , Great North Children's Hospital, Newcastle University (Author)
  • Andrew R. Gennery - , Great North Children's Hospital, Newcastle University (Author)


X-linked chronic granulomatous disease (XL-CGD) is an inherited disorder of superoxide production, causing failure to generate the oxidative burst in phagocytes. It is characterized by invasive bacterial and fungal infections, inflammation, and chronic autoimmune disease. While XL-CGD carriers were previously assumed to be healthy, a range of clinical manifestations with significant morbidity have recently been described in a subgroup of carriers with impaired neutrophil oxidative burst due to skewed lyonization. Allogeneic hematopoietic stem cell transplantation (HSCT) is the standard curative treatment for CGD but has rarely been reported in individual symptomatic carriers to date. We undertook a retrospective international survey of outcome of HSCT for symptomatic XL-CGD carriers. Seven symptomatic female XL-CGD carriers aged 1–56 years underwent HSCT in four centers, indicated for severe and recurrent infection, colitis, and autoimmunity. Two patients died from transplant-related complications, following donor engraftment and restoration of oxidative burst. All surviving patients demonstrated resolution of their neutrophil oxidative burst defect with concordant reduction in infection and inflammatory symptoms and freedom from further immunosuppressive therapy. In conclusion, allogeneic HSCT may cure the phagocyte defect in symptomatic XL-CGD carriers and improve their recurrent and disabling infective and inflammatory symptoms but risks transplant-related complications.


Original languageEnglish
Pages (from-to)1964-1973
Number of pages10
JournalJournal of clinical immunology
Issue number8
Publication statusPublished - Nov 2023

External IDs

Mendeley 656ed7ae-2915-325f-89a5-5fe59d52a948
ORCID /0009-0003-6519-0482/work/147142933
PubMed 37620741


ASJC Scopus subject areas


  • Allogeneic HSCT, Chronic granulomatous disease, Lyonization, X-linked carrier, Granulomatous Disease, Chronic/diagnosis, Respiratory Burst, Humans, Neutrophils, Hematopoietic Stem Cell Transplantation, Female, Retrospective Studies