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J Clin Immunol. 2015 Aug;35(6):538-49. doi: 10.1007/s10875-015-0186-9. Epub 2015 Aug 14.

Nijmegen Breakage Syndrome: Clinical and Immunological Features, Long-Term Outcome and Treatment Options - a Retrospective Analysis.

Author information

1
Department of Immunology, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland. bwolska@interia.pl.
2
Department of Microbiology and Clinical Immunology, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
3
Department of Medical Genetics, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
4
Histocompatibility Laboratory, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
5
Department of Immunology, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
6
Gastrology, Hepatology Department, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
7
Western-Ukrainian Centre of Paediatric Immunology, Western Ukrainian Specialized Children's Medical Centre, Dnisterska Street, 27, Lviv, 79035, Ukraine.
8
Pediatric Immunology, Mother and Child Health Institute, Medical School, University of Belgrade, Radoja Dakica 6-8, 11070, Belgrade, Serbia.
9
Department of Infectious and Pediatric Immunology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary.
10
University Childrens Hospital, Ludwig Maximilians University, Lindwurmstrasse 4, 80337, Munich, Germany.
11
1st Pediatric Department, Comenius University Medical Faculty, Children University Hospital, Mickiewiczova 13th, Bratislava, 813 69, Slovakia.
12
Department of Сlinical Immunology and Allergy, Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, 1 Samori Mashela Str., Moscow, 117917, Russia.
13
Department of Paediatric Immunology, Uludag University School of Medicine, Özlüce Mh., 16120, Bursa, Turkey.
14
Department of Pediatric Pulmonology and Neonatology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
15
Department of Pediatrics and Adolescent Medicine, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
16
Division of Pediatric Hematology-Oncology, Department of Pediatric and Adolescent Medicine, Medical University Graz, Auenbruggerplatz 38, 8036, Graz, Austria.
17
Institute of Cellular Medicine, Child Health, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
18
Department of Paediatric Rehabilitation, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
19
Department of Pediatrics and Developmental Disorders of Children and Adolescents, Medical University Bialystok, 15-089 Jana Kilinskiego str. 1, Białystok, Poland.
20
Department of Pediatric Hematology, Oncology and BMT, Wroclaw Medical University, 50-368 Bujwida Str. 44, Wroclaw, Poland.
21
Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Curie-Skłodowskiej 9 str., Bydgoszcz, Poland.
22
Department of Pediatric Hematology, Oncology and Haematopoietic Stem Cell Transplantation, University of Medical Sciences, Poznań, 60-572 Szpitalna str. 27/33, Poznań, Poland.
23
Department of Pediatric Hematology, Oncology and Transplantology, Medical University, Lublin, 20-093 W. Chodźki str. 2, Lublin, Poland.
24
Department of Oncology, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
25
Centre of Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, Robert-Koch-Str. 1, 79106, Freiburg, Germany.
26
Department of Pediatric Hematology/Oncology, Dr. von Hauner University Children's Hospital, Lindwurmstraße 4, 80337, Munich, Germany.

Abstract

PURPOSE:

Nijmegen Breakage Syndrome (NBS) is a rare inherited condition, characterized by microcephaly, chromosomal instability, immunodeficiency, and predisposition to malignancy. This retrospective study, characterizing the clinical and immunological status of patients with NBS at time of diagnosis, was designed to assess whether any parameters were useful in disease prognosis, and could help determine patients qualified for hematopoietic stem cell transplantation.

METHODS:

The clinical and immunological characteristics of 149 NBS patients registered in the online database of the European Society for Immune Deficiencies were analyzed.

RESULTS:

Of the 149 NBS patients, 91 (61%), of median age 14.3 years, remained alive at the time of analysis. These patients were clinically heterogeneous, with variable immune defects, ranging from negligible to severe dysfunction. Humoral deficiencies predisposed NBS patients to recurrent/chronic respiratory tract infections and worsened long-term clinical prognosis. Eighty malignancies, most of lymphoid origin (especially non-Hodgkin's lymphomas), were diagnosed in 42% of patients, with malignancy being the leading cause of death in this cohort. Survival probabilities at 5, 10, 20 and 30 years of age were 95, 85, 50 and 35%, respectively, and were significantly lower in patients with than without malignancies.

CONCLUSIONS:

The extremely high incidence of malignancies, mostly non-Hodgkin's lymphomas, was the main risk factor affecting survival probability in NBS patients. Because treatment of NBS is very difficult and frequently unsuccessful, the search for an alternative medical intervention such as hematopoietic stem cell transplantation is of great clinical importance.

KEYWORDS:

Nijmegen breakage syndrome; chromosomal instability; hematopoietic stem cell transplantation; non-Hodgkin’s lymphoma; primary immunodeficiencies

PMID:
26271390
DOI:
10.1007/s10875-015-0186-9
[Indexed for MEDLINE]

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