Nijmegen Breakage Syndrome: Clinical and Immunological Features, Long-Term Outcome and Treatment Options - a Retrospective Analysis.
OBJECTIVE
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.
Department of Immunology, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland. bwolska@interia.pl.
Beata
B
Wolska-Kuśnierz
Department of Microbiology and Clinical Immunology, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
Hanna
H
Gregorek
Department of Medical Genetics, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
Krystyna
K
Chrzanowska
Histocompatibility Laboratory, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
Barbara
B
Piątosa
Department of Immunology, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
Barbara
B
Pietrucha
Department of Immunology, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
Edyta
E
Heropolitańska-Pliszka
Department of Immunology, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
Małgorzata
M
Pac
Gastrology, Hepatology Department, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
Maja
M
Klaudel-Dreszler
Western-Ukrainian Centre of Paediatric Immunology, Western Ukrainian Specialized Children's Medical Centre, Dnisterska Street, 27, Lviv, 79035, Ukraine.
Larysa
L
Kostyuchenko
Pediatric Immunology, Mother and Child Health Institute, Medical School, University of Belgrade, Radoja Dakica 6-8, 11070, Belgrade, Serbia.
Srdjan
S
Pasic
Department of Infectious and Pediatric Immunology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary.
Laszlo
L
Marodi
University Childrens Hospital, Ludwig Maximilians University, Lindwurmstrasse 4, 80337, Munich, Germany.
Bernd H
BH
Belohradsky
1st Pediatric Department, Comenius University Medical Faculty, Children University Hospital, Mickiewiczova 13th, Bratislava, 813 69, Slovakia.
Peter
P
Čižnár
Department of Сlinical Immunology and Allergy, Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, 1 Samori Mashela Str., Moscow, 117917, Russia.
Anna
A
Shcherbina
Department of Paediatric Immunology, Uludag University School of Medicine, Özlüce Mh., 16120, Bursa, Turkey.
Sara Sebnem
SS
Kilic
Department of Pediatric Pulmonology and Neonatology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Ulrich
U
Baumann
Department of Pediatrics and Adolescent Medicine, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.|Division of Pediatric Hematology-Oncology, Department of Pediatric and Adolescent Medicine, Medical University Graz, Auenbruggerplatz 38, 8036, Graz, Austria.
Markus G
MG
Seidel
Institute of Cellular Medicine, Child Health, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Andrew R
AR
Gennery
Department of Paediatric Rehabilitation, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
Małgorzata
M
Syczewska
Department of Pediatrics and Developmental Disorders of Children and Adolescents, Medical University Bialystok, 15-089 Jana Kilinskiego str. 1, Białystok, Poland.
Bożena
B
Mikołuć
Department of Pediatric Hematology, Oncology and BMT, Wroclaw Medical University, 50-368 Bujwida Str. 44, Wroclaw, Poland.
Krzysztof
K
Kałwak
Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Curie-Skłodowskiej 9 str., Bydgoszcz, Poland.
Jan
J
Styczyński
Department of Pediatric Hematology, Oncology and Haematopoietic Stem Cell Transplantation, University of Medical Sciences, Poznań, 60-572 Szpitalna str. 27/33, Poznań, Poland.
Anna
A
Pieczonka
Department of Pediatric Hematology, Oncology and Transplantology, Medical University, Lublin, 20-093 W. Chodźki str. 2, Lublin, Poland.
Katarzyna
K
Drabko
Department of Oncology, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
Anna
A
Wakulińska
Centre of Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, Robert-Koch-Str. 1, 79106, Freiburg, Germany.
Benjamin
B
Gathmann
Department of Pediatric Hematology/Oncology, Dr. von Hauner University Children's Hospital, Lindwurmstraße 4, 80337, Munich, Germany.
Michael H
MH
Albert
Department of Immunology, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
Urszula
U
Skarżyńska
Department of Immunology, Children's Memorial Health Institute, 04-730 Av. Dzieci Polskich 20, Warsaw, Poland.
Ewa
E
Bernatowska
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D043171:Chromosomal Instability; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007153:Immunologic Deficiency Syndromes; D007223:Infant; D008228:Lymphoma, Non-Hodgkin; D008297:Male; D008831:Microcephaly; D049932:Nijmegen Breakage Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult
Nijmegen breakage syndrome; chromosomal instability; hematopoietic stem cell transplantation; non-Hodgkin’s lymphoma; primary immunodeficiencies