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

M. Teresa de la Morena*, David Leonard, Troy R. Torgerson, Otavio Cabral-Marques, Mary Slatter, Asghar Aghamohammadi, Sharat Chandra, Luis Murguia-Favela, Francisco A. Bonilla, Maria Kanariou, Rongras Damrongwatanasuk, Caroline Y. Kuo, Christopher C. Dvorak, Isabelle Meyts, Karin Chen, Lisa Kobrynski, Neena Kapoor, Darko Richter, Daniela DiGiovanni, Fatima DhallaEvangelia Farmaki, Carsten Speckmann, Teresa Español, Anna Shcherbina, Imelda Celine Hanson, Jiri Litzman, John M. Routes, Melanie Wong, Ramsay Fuleihan, Suranjith L. Seneviratne, Trudy N. Small, Ales Janda, Liliana Bezrodnik, Reinhard Seger, Andrea Gomez Raccio, J. David M Edgar, Janet Chou, Jordan K. Abbott, Joris van Montfrans, Luis Ignacio González-Granado, Nancy Bunin, Necil Kutukculer, Paul Gray, Gisela Seminario, Srdjan Pasic, Victor Aquino, Christian Wysocki, Hassan Abolhassani, Morna Dorsey, Charlotte Cunningham-Rundles, Alan P. Knutsen, John Sleasman, Beatriz Tavares Costa Carvalho, Antonio Condino-Neto, Eyal Grunebaum, Helen Chapel, Hans D. Ochs, Alexandra Filipovich, Mort Cowan, Andrew Gennery, Andrew Cant, Luigi D. Notarangelo, Chaim M. Roifman

*Corresponding author for this work

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1282-1292
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume139
Issue number4
DOIs
StatePublished - Apr 1 2017

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Keywords

  • CD40 ligand
  • Karnofsky/Lansky scores
  • X-linked hyper-IgM syndrome
  • defects in class-switch recombination
  • hematopoietic cell transplantation
  • long-term outcomes
  • primary immunodeficiency

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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., ... Roifman, C. M. (2017). Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation. Journal of Allergy and Clinical Immunology, 139(4), 1282-1292. https://doi.org/10.1016/j.jaci.2016.07.039