Primary immunodeficiencies
Chronic granulomatous disease: Overview and hematopoietic stem cell transplantation

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Chronic granulomatous disease (CGD) still causes significant morbidity and mortality. The difficulty in considering high-risk yet curative treatments, such as allogeneic bone marrow transplantation, lies in the unpredictable courses of both CGD and bone marrow transplantation in different patients. Some patients with CGD can have frequent infections, granulomatous or autoimmune disorders necessitating immunosuppressive therapy, or both but also experience long periods of relative good health. However, the risk of death is clearly higher in patients with CGD of all types, and the complications of CGD short of death can still cause significant morbidity. Therefore, with recent developments and improvements, bone marrow transplantation, previously considered an experimental or high-risk procedure, has emerged as an important option for patients with CGD. We will discuss the complications of CGD that result in significant morbidity and mortality, particularly the most common infections and autoimmune/inflammatory complications, as well as their typical management. We will then discuss the status of bone marrow transplantation.

Section snippets

Infection

Despite the significant progress made in antibiotic and antifungal therapy and prophylaxis, patients with CGD still have serious infections. Most large studies have shown an infection rate of around 0.15 to 0.3 per year.4, 5, 6 The US National Institutes of Health (NIH) has followed more than 250 patients with CGD over almost 40 years, the majority of whom were given diagnoses after infections of the skin, lymph node, lung, or liver. A small group of patients (approximately 5%) were identified

Inflammatory complications and autoimmunity in patients with CGD

Dysregulated inflammation in patients with CGD typically occurs in response to a trigger and might be due to either increased proinflammatory or decreased anti-inflammatory mediators. Patients with CGD frequently experience inflammatory complications, and some might have autoimmune problems.30

Other than infection, a characteristic feature of CGD is granulomatous inflammation. CGD granulomas are typically noncaseating, are composed of multinucleated giant cells, and can be found in multiple

Hematopoietic stem cell transplantation for patients with CGD

Currently, the only known cure for CGD is allogeneic hematopoietic cell transplantation. Historically, this has only been reluctantly offered because of the risks of procedure-related morbidity and mortality. Additionally, unrelated donor transplantations were riskier than sibling transplantations, and the pool of donors was limited. From 1973, when the first CGD bone marrow transplant was performed, until now, the results of 99 transplantations, not including cord blood recipients, have been

Discussion

Allogeneic stem cell transplantation for CGD is becoming more common and reflects increased overall success. Survival has increased from approximately 85% before 2000 to 90% to 95% based on recently reported outcomes and our own results, even with the use of unrelated donors. In fact, outcomes with perfectly HLA-matched unrelated donors appear to approach, if not equal, those using HLA sibling donors. This suggests that donor availability should not be limiting for transplantation in patients

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    Series editors: Donald Y. M. Leung, MD, PhD, and Dennis K. Ledford, MD

    Supported by the Intramural Research Program of the NIH, the National Institute of Allergy and Infectious Diseases.

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