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Allogeneic HSCT for Symptomatic Female X-linked Chronic Granulomatous Disease Carriers
Christo Tsilifis1,2, Tuulia Torppa3, Eleri J Williams4
1Paediatric Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Ward 3, Newcastle Upon Tyne, NE1 4LP, UK. c.tsilifis@nhs.net.
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Hematopoietic stem cell transplantation (HSCT) can cure symptomatic X-linked chronic granulomatous disease (XL-CGD) carriers by restoring neutrophil oxidative burst, reducing infections and inflammation, despite transplant risks.
Area of Science:
- Immunology
- Genetics
- Hematology
Background:
- X-linked chronic granulomatous disease (XL-CGD) is an inherited phagocyte disorder affecting superoxide production.
- XL-CGD carriers were thought to be asymptomatic, but some exhibit morbidity due to skewed lyonization and impaired oxidative burst.
- Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for XL-CGD but rarely used in symptomatic carriers.
Purpose of the Study:
- To evaluate the outcomes of allogeneic HSCT in symptomatic female XL-CGD carriers.
- To assess the efficacy of HSCT in resolving infections, inflammation, and autoimmunity in this patient subgroup.
Main Methods:
- Retrospective international survey of seven symptomatic XL-CGD carriers (aged 1-56 years) who underwent HSCT across four centers.
- Data collected on indications for HSCT, transplant complications, engraftment, oxidative burst restoration, and clinical outcomes.
Main Results:
- Two of seven patients died from transplant-related complications.
- Surviving patients showed restored neutrophil oxidative burst, reduced infections, and decreased inflammatory symptoms.
- HSCT led to resolution of colitis and autoimmunity, with cessation of immunosuppressive therapy in survivors.
Conclusions:
- Allogeneic HSCT can be a curative option for symptomatic XL-CGD carriers, effectively addressing phagocyte defects and associated severe symptoms.
- While HSCT offers significant clinical improvement, it carries risks of transplant-related complications that must be carefully managed.
Abstract:
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.
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