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J Allergy Clin Immunol. 2017 Apr;139(4):1282-1292. doi: 10.1016/j.jaci.2016.07.039. Epub 2016 Sep 30.

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

Author information

1
University of Texas Southwestern Medical Center and Children's Medical Center, Children's Health, Dallas, Tex. Electronic address: maite.delamorena@utsouthwestern.edu.
2
University of Texas Southwestern Medical Center and Children's Medical Center, Children's Health, Dallas, Tex.
3
University of Washington and Seattle Children's Research Institute, Seattle, Wash.
4
Department of Rheumatology, University of Lübeck, Lübeck, Germany.
5
Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
6
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
7
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
8
Hospital for Sick Children, Toronto, Ontario, Canada.
9
Boston Children's Hospital, Boston, Mass.
10
Sophia Children's Hospital Athens, Athens, Greece.
11
University of South Florida, All Childrens FL, St Petersburg, Fla.
12
Geffen SOM at David Geffen School of Medicine at UCLA, Los Angeles, Calif.
13
UC San Francisco, San Francisco, Calif.
14
University Hospitals Leuven, Leuven, Belgium.
15
University of Utah School of Medicine, Salt Lake City, Utah.
16
Emory University, Atlanta, Ga.
17
Children's Hospital Los Angeles, Keck School of Medicine, Los Angeles, Calif.
18
University Hospital Center, Zagreb, Croatia.
19
Hospital de Niños Dr Ricardo Gutierrez, Buenos Aires, Argentina.
20
University of Oxford, Oxford, United Kingdom.
21
Ippokration General Hospital, Thessaloniki, Greece.
22
Department of Pediatrics and Adolescent Medicine, Center for Chronic Immunodeficiency University Medical Center, Freiburg, Germany.
23
Hospital Vall d'Hebron, Barcelona, Spain.
24
Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
25
Baylor/Texas Children's Hospital, Houston, Tex.
26
Department of Clinical Immunology and Allergology, St Anne's University Hospital in Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
27
Children's Hospital of Wisconsin, Milwaukee, Wis.
28
Children's Hospital at Westmead, Sydney, Australia.
29
Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Ill.
30
Royal Free Hospital, London, United Kingdom.
31
Memorial Sloan-Kettering Cancer Center, New York, NY.
32
University Hospital Motol, Prague, Czech Republic.
33
Lucerne, Switzerland.
34
Regional Immunology Service, Belfast, United Kingdom.
35
Children's Hospital Boston, Boston, Mass.
36
National Jewish Health, Denver, Colo.
37
Division Pediatrics, Pediatrische Immunologie en Infectieziekten, Wilhelmina Children's Hospital, UMC Utrecht, Utrecht, The Netherlands.
38
Unidad de Immunodeficiencias Primarias y la Unidad de Hematología y Oncología Pediátrica, Instituto de Investigacíon Hospital 12 de Octubre, Madrid, Spain.
39
Children's Hospital of Philadelphia, Philadelphia, Pa.
40
Ege University Faculty of Medicine, Izmir, Turkey.
41
Sydney Children's Hospital, Randwick, Australia.
42
Mother & Child Health Institute, Belgrade, Serbia.
43
Mount Sinai Hospital, New York, NY.
44
Saint Louis University, St Louis, Mo.
45
Duke University, Durham, NC.
46
Division of Allergy-Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil.
47
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
48
Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Md.

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.

KEYWORDS:

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

PMID:
27697500
PMCID:
PMC5374029
DOI:
10.1016/j.jaci.2016.07.039
[Indexed for MEDLINE]
Free PMC Article

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