期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 143, 期 6, 页码 2238-2253出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2018.12.1010
关键词
CD40 ligand; hematopoietic stem cell transplantation; X-linked hyper-IgM syndrome; primary immunodeficiency
资金
- ESID Medium Term Fellowship
- Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID)
- Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Bethesda, Maryland [U54-AI082973, R13-AI094943]
- CEREDIH
- French Ministry of Health
- National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust
- Newcastle University
Background: CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary, Pneumocystis and Cryptosporidium species infections. Long-term survival with supportive therapy is poor. Currently, the only curative treatment is hematopoietic stem cell transplantation (HSCT). Objective: We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics. Methods: We retrospectively collected data on 130 patients who underwent HSCT for CD40L deficiency between 1993-2015. We analyzed outcome and variables' relevance with respect to survival and cure. Results: Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were 78.2%, 58.1%, and 72.3% 5 years after HSCT. Results were better in transplantations performed in 2000 or later and in children less than 10 years old at the time of HSCT. Pre-existing organ damage negatively influenced outcome. Sclerosing cholangitis was the most important risk factor. After 2000, superior OS was achieved with matched donors. Use of myeloablative regimens and HSCT at 2 years or less from diagnosis associated with higher OS and DFS. EFS was best with matched sibling donors, myeloablative conditioning (MAC), and bone marrow-derived stem cells. Most rejections occurred after reduced-intensity or nonmyeloablative conditioning, which associated with poor donor cell engraftment. Mortality occurred mainly early after HSCT, predominantly from infections. Among survivors who ceased immunoglobulin replacement, T-lymphocyte chimerism was 50% or greater donor in 85.2%. Conclusion: HSCT is curative in patients with CD40L deficiency, with improved outcome if performed before organ damage development. MAC is associated with better OS, EFS, and DFS. Prospective studies are required to compare the risks of HSCT with those of lifelong supportive therapy.
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