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

• Type of Material: Article
• Authors: M. Teresa de la Morena, University of Texas Southwestern Medical Center; David Leonard, University of Texas Southwestern Medical Center; Troy R. Torgerson, University of Washington; Otavio Cabral-Marques, University of Lubeck; Mary Slatter, Royal Victoria Infirmary; Asghar Aghamohammadi, Tehran University of Medical Sciences; Sharat Chandra, Cincinnati Children’s Hospital Medical Center; Luis Murguia-Favela, Hospital for Sick Children; Francisco A. Bonilla, Boston Children’s Hospital; Maria Kanariou, Sophia Children’s Hospital Athens; Rongras Damrongwatanasuk, University of South Florida; Caroline Y. Kuo, UCLA; Christopher C. Dvorak, UC San Francisco; Isabelle Meyts, University Hospitals Leuven; Karin Chen, University of Utah; Lisa Kobrynski, Emory University; Neena Kapoor, Children’s Hospital Los Angeles; Darko Richter, University Hospital Center, Zagreb; Daniela DiGiovanni, Hospital de Niños; Fatima Dhalla, University of Oxford; Evangelia Farmaki, Ippokration General Hospital; Carsten Speckmann, Center for Chronic Immunodeficiency University Medical Center, Freiburg; Teresa Espanol, Hospital Vall d’Hebron; Anna Scherbina, Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow; Imelda Celine Hanson, Baylor/Texas Children’s Hospital, Houston; Jiri Litzman, St Anne’s University Hospital in Brno; John M. Routes, Children’s Hospital of Wisconsin; Melanie Wong, Children’s Hospital at Westmead; Ramsay Fuleihan, Ann and Robert H Lurie Children’s Hospital of Chicago; Suranjith L. Seneviratne, Royal Free Hospital, London; Trudy N. Small, Memorial Sloan-Kettering Cancer Center; Ales Janda, University Hospital Motol, Prague; Liliana Bezrodnik, Hospital de Niños; Reinhard Seger, Lucerne, Switzerland; Andrea Gomez Raccio, Hospital de Niños; J. David M. Edgar, Regional Immunology Service, Belfast; Janet Chou, Children’s Hospital Boston; Jordan K. Abbott, National Jewish Health, Denver; Joris van Montfrans, UMC Utrecht; Luis Ignacio Gonzalez-Granado, Instituto de Investigacíon Hospital; Nancy Bunin, Children’s Hospital of Philadelphia; Necil Kutukculer, Ege University; Paul Gray, Sydney Children’s Hospital; Gisela Seminario, Hospital de Niños; Srdjan Pasic, Mother & Child Health Institute, Belgrade; Victor Aquino, University of Texas Southwestern Medical Center; Christian Wysocki, University of Texas Southwestern Medical Center; Hassan Abolhassani, Tehran University of Medical Sciences; Morna Dorsey, UC San Francisco; Charlotte Cunningham-Rundles, Mount Sinai Hospital; Alan P. Knutsen, Saint Louis University; John Sleasman, Duke University, Durham; Beatriz Tavares Costa Carvalho, Federal University of São Paulo; Antonio Condino-Neto, University of São Paulo; Eyal Grunebaum, the Hospital for Sick Children, Toronto; Helen Chapel, University of Oxford; Hans D. Ochs, University of Washington and Seattle Children’s Research Institute; Alexandra Filipovich, Cincinnati Children’s Hospital Medical Center; Mort Cowan, UC San Francisco; Andrew Gennery, Royal Victoria Infirmary, Newcastle upon Tyne; Andrew Cant, Royal Victoria Infirmary, Newcastle upon Tyne; Luigi D. Notarangelo, National Institutes of Health; Chaim Roifman, the Hospital for Sick Children, Toronto
• Language: English
• Date: 2017-04
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 American Academy of Allergy, Asthma & Immunology
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jaci.2016.07.039
• Title of Journal or Parent Work: Journal of Allergy and Clinical Immunology
• ISSN: 0091-6749
• Volume: 139
• Issue: 4
• Start Page: 1282
• End Page: 1292
• Grant/Funding Information: Supported by a grant from Jeffrey Modell Foundation (to M.d.l.M.).; The Primary Immune Deficiency Treatment Consortium (PIDTC) is supported by the National Institutes of Health Office of Rare Diseases, National Center for Advancing Translational Sciences and National, Institute of Allergy and Infectious Disease grants U54 AI 082973 and R13AI094943.
• Keywords: CHRONIC GRANULOMATOUS-DISEASE; Allergy; BONE-MARROW-TRANSPLANTATION; CD40 LIGAND DEFICIENCY; T-CELLS; hematopoietic cell transplantation; primary immunodeficiency; long-term outcomes; Karnofsky/Lansky scores; EUROPEAN EXPERIENCE; Life Sciences & Biomedicine; PRIMARY IMMUNODEFICIENCY DISEASES; CD40 ligand; X-linked hyper-IgM syndrome; Science & Technology; WISKOTT-ALDRICH-SYNDROME; HYPERIMMUNOGLOBULINEMIA-M; defects in class-switch recombination; SINGLE-CENTER EXPERIENCE; Immunology; DEFECTIVE EXPRESSION
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

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.