Published Online: January 14, 2015
Immunodeficiency can be defined as a breakdown of the immune system. Common variable immunodeficiency (CVID) is the most frequent immunodeficiency, and is characterized by recurrent infections (e.g. sinusitis, bronchitis) and reduced antibody (immunoglobulin) levels. Most patients have a good prognosis and quality of life once they receive treatment with immunoglobulin substitution. However, some CVID patients have a more severe dysregulation of the immune system associated with enlarged lymph nodes, chronic diarrhea, lung disease or blood count abnormalities. It was observed that the latter have a compromised life expectancy, despite immunoglobulin treatment. In addition, some CVID patients have a higher risk of developing malignant disease. As the cells responsible for the immune system are generated in the bone marrow, curing CVID seems possible with bone marrow transplantation or stem cell transplantation (HSCT), as has been well established for other immunodeficiencies.
Recently published in The Journal of Allergy and Clinical Immunology (JACI), Wehr and colleagues conducted the first study summarizing the experience of HSCT in patients with CVID. Fourteen centers from Europe, the US, and Japan contributed 25 patients, all of which were transplanted in the last two decades.
All surviving patients had a complete or partial resolution of the condition they were transplanted for, e.g. lymphoma was cured, gastrointestinal disease resolved or lung disease ameliorated. However, 52% of patients (13/25 patients) died within 20 months after transplantation. The high mortality was most likely due to the severe illness of some patients at the time of HSCT and due to the fact that transplantation was considered too late as a treatment option.
In contrast, CVID patients transplanted for lymphoma had a better survival rate (83%, 5/6 patients) and all surviving patients were cured from the lymphoma.
A serious complication of HSCT is graft-versus-host-disease (GvHD), which is the attack of transplanted cells on the recipient’s cells. For unknown reasons, in CVID patients the frequency and severity of GVHD was higher than expected, based on other studies transplanting non-CVID patients.
Interestingly, only half of the surviving patients were cured from the antibody deficiency and the other half remained on immunoglobulin replacement despite a successful reconstitution with the donor’s immune system. This observation suggests that in some patients there might be contributing factors to the origin of CVID outside of the hematopoietic system.
In conclusion, severe complications from CVID of the gastrointestinal tract or the lung may improve with HSCT, and potentially the antibody deficiency can be cured. However, in the last two decades the procedure has been associated with a high mortality rate and a high incidence of GvHD. Therefore careful patient selection and refinement of the transplantation procedure is critical and needs further study. A study initiative by the authors is underway.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.