Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation Journal Article


Authors: de la Morena, M. T.; Leonard, D.; Torgerson, T. R.; Cabral-Marques, O.; Slatter, M.; Aghamohammadi, A.; Chandra, S.; Murguia-Favela, L.; Bonilla, F. A.; Kanariou, M.; Damrongwatanasuk, R.; Kuo, C. Y.; Dvorak, C. C.; Meyts, I.; Chen, K.; Kobrynski, L.; Kapoor, N.; Richter, D.; DiGiovanni, D.; Dhalla, F.; Farmaki, E.; Speckmann, C.; Español, T.; Shcherbina, A.; Hanson, I. C.; Litzman, J.; Routes, J. M.; Wong, M.; Fuleihan, R.; Seneviratne, S. L.; Small, T. N.; Janda, A.; Bezrodnik, L.; Seger, R.; Raccio, A. G.; Edgar, J. D. M.; Chou, J.; Abbott, J. K.; van Montfrans, J.; González-Granado, L. I.; Bunin, N.; Kutukculer, N.; Gray, P.; Seminario, G.; Pasic, S.; Aquino, V.; Wysocki, C.; Abolhassani, H.; Dorsey, M.; Cunningham-Rundles, C.; Knutsen, A. P.; Sleasman, J.; Costa Carvalho, B. T.; Condino-Neto, A.; Grunebaum, E.; Chapel, H.; Ochs, H. D.; Filipovich, A.; Cowan, M.; Gennery, A.; Cant, A.; Notarangelo, L. D.; Roifman, C. M.
Article Title: Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation
Abstract: Background X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency with high morbidity and mortality compared with those seen in healthy subjects. Hematopoietic cell transplantation (HCT) has been considered a curative therapy, but the procedure has inherent complications and might not be available for all patients. Objectives We sought to collect data on the clinical presentation, treatment, and follow-up of a large sample of patients with XHIGM to (1) compare long-term overall survival and general well-being of patients treated with or without HCT along with clinical factors associated with mortality and (2) summarize clinical practice and risk factors in the subgroup of patients treated with HCT. Methods Physicians caring for patients with primary immunodeficiency diseases were identified through the Jeffrey Modell Foundation, United States Immunodeficiency Network, Latin American Society for Immunodeficiency, and Primary Immune Deficiency Treatment Consortium. Data were collected with a Research Electronic Data Capture Web application. Survival from time of diagnosis or transplantation was estimated by using the Kaplan-Meier method compared with log-rank tests and modeled by using proportional hazards regression. Results Twenty-eight clinical sites provided data on 189 patients given a diagnosis of XHIGM between 1964 and 2013; 176 had valid follow-up and vital status information. Sixty-seven (38%) patients received HCT. The average follow-up time was 8.5 ± 7.2 years (range, 0.1-36.2 years). No difference in overall survival was observed between patients treated with or without HCT (P = .671). However, risk associated with HCT decreased for diagnosis years 1987-1995; the hazard ratio was significantly less than 1 for diagnosis years 1995-1999. Liver disease was a significant predictor of overall survival (hazard ratio, 4.9; 95% confidence limits, 2.2-10.8; P < .001). Among survivors, those treated with HCT had higher median Karnofsky/Lansky scores than those treated without HCT (P < .001). Among patients receiving HCT, 27 (40%) had graft-versus-host disease, and most deaths occurred within 1 year of transplantation. Conclusion No difference in survival was observed between patients treated with or without HCT across all diagnosis years (1964-2013). However, survivors treated with HCT experienced somewhat greater well-being, and hazards associated with HCT decreased, reaching levels of significantly less risk in the late 1990s. Among patients treated with HCT, treatment at an early age is associated with improved survival. Optimism remains guarded as additional evidence accumulates. © 2016 American Academy of Allergy, Asthma & Immunology
Keywords: cd40 ligand; primary immunodeficiency; hematopoietic cell transplantation; long-term outcomes; defects in class-switch recombination; karnofsky/lansky scores; x-linked hyper-igm syndrome
Journal Title: Journal of Allergy and Clinical Immunology
Volume: 139
Issue: 4
ISSN: 0091-6749
Publisher: Mosby Elsevier  
Date Published: 2017-04-01
Start Page: 1282
End Page: 1292
Language: English
DOI: 10.1016/j.jaci.2016.07.039
PROVIDER: scopus
PMCID: PMC5374029
PUBMED: 27697500
DOI/URL:
Notes: Article -- Export Date: 2 May 2017 -- Source: Scopus
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  1. Trudy Small
    215 Small