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Journal of Clinical Immunology

, Volume 35, Issue 6, pp 538–549 | Cite as

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

  • Beata Wolska-Kuśnierz
  • Hanna Gregorek
  • Krystyna Chrzanowska
  • Barbara Piątosa
  • Barbara Pietrucha
  • Edyta Heropolitańska-Pliszka
  • Małgorzata Pac
  • Maja Klaudel-Dreszler
  • Larysa Kostyuchenko
  • Srdjan Pasic
  • Laszlo Marodi
  • Bernd H. Belohradsky
  • Peter Čižnár
  • Anna Shcherbina
  • Sara Sebnem Kilic
  • Ulrich Baumann
  • Markus G. Seidel
  • Andrew R. Gennery
  • Małgorzata Syczewska
  • Bożena Mikołuć
  • Krzysztof Kałwak
  • Jan Styczyński
  • Anna Pieczonka
  • Katarzyna Drabko
  • Anna Wakulińska
  • Benjamin Gathmann
  • Michael H. Albert
  • Urszula Skarżyńska
  • Ewa Bernatowska
  • on behalf of the Inborn Errors Working Party of the Society for European Blood and Marrow Transplantation and the European Society for Immune Deficiencies
Original Research

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 primary immunodeficiencies chromosomal instability hematopoietic stem cell transplantation non-Hodgkin’s lymphoma 

Notes

Acknowledgments

This work was supported in part by grant N N407 1714 34 from the Polish Ministry of Science and Higher Education and by internal grant no. S123/2012 funded by the CMHI, Warsaw, Poland.

Conflict of Interests

Urszula Skarżyńska was supported by EURO-GENE-SCAN 223293 grant, Benjamin Gathmann has served as an ESID Online Database Coordinator, which is supported by industry. The remaining authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Beata Wolska-Kuśnierz
    • 1
  • Hanna Gregorek
    • 2
  • Krystyna Chrzanowska
    • 3
  • Barbara Piątosa
    • 4
  • Barbara Pietrucha
    • 1
  • Edyta Heropolitańska-Pliszka
    • 1
  • Małgorzata Pac
    • 1
  • Maja Klaudel-Dreszler
    • 5
  • Larysa Kostyuchenko
    • 6
  • Srdjan Pasic
    • 7
  • Laszlo Marodi
    • 8
  • Bernd H. Belohradsky
    • 9
  • Peter Čižnár
    • 10
  • Anna Shcherbina
    • 11
  • Sara Sebnem Kilic
    • 12
  • Ulrich Baumann
    • 13
  • Markus G. Seidel
    • 14
    • 15
  • Andrew R. Gennery
    • 16
  • Małgorzata Syczewska
    • 17
  • Bożena Mikołuć
    • 18
  • Krzysztof Kałwak
    • 19
  • Jan Styczyński
    • 20
  • Anna Pieczonka
    • 21
  • Katarzyna Drabko
    • 22
  • Anna Wakulińska
    • 23
  • Benjamin Gathmann
    • 24
  • Michael H. Albert
    • 25
  • Urszula Skarżyńska
    • 1
  • Ewa Bernatowska
    • 1
  • on behalf of the Inborn Errors Working Party of the Society for European Blood and Marrow Transplantation and the European Society for Immune Deficiencies
  1. 1.Department of ImmunologyChildren’s Memorial Health InstituteWarsawPoland
  2. 2.Department of Microbiology and Clinical ImmunologyChildren’s Memorial Health InstituteWarsawPoland
  3. 3.Department of Medical GeneticsChildren’s Memorial Health InstituteWarsawPoland
  4. 4.Histocompatibility LaboratoryChildren’s Memorial Health InstituteWarsawPoland
  5. 5.Gastrology, Hepatology DepartmentChildren’s Memorial Health InstituteWarsawPoland
  6. 6.Western-Ukrainian Centre of Paediatric ImmunologyWestern Ukrainian Specialized Children’s Medical CentreLvivUkraine
  7. 7.Pediatric Immunology, Mother and Child Health Institute, Medical SchoolUniversity of BelgradeBelgradeSerbia
  8. 8.Department of Infectious and Pediatric Immunology, Medical and Health Science CenterUniversity of DebrecenDebrecenHungary
  9. 9.University Childrens HospitalLudwig Maximilians UniversityMunichGermany
  10. 10.1st Pediatric Department, Comenius University Medical FacultyChildren University HospitalBratislavaSlovakia
  11. 11.Department of Сlinical Immunology and AllergyResearch and Clinical Center for Pediatric Hematology, Oncology and ImmunologyMoscowRussia
  12. 12.Department of Paediatric ImmunologyUludag University School of MedicineBursaTurkey
  13. 13.Department of Pediatric Pulmonology and NeonatologyMedical School HannoverHannoverGermany
  14. 14.Department of Pediatrics and Adolescent Medicine, St. Anna Children’s HospitalMedical University of ViennaViennaAustria
  15. 15.Division of Pediatric Hematology-Oncology, Department of Pediatric and Adolescent MedicineMedical University GrazGrazAustria
  16. 16.Institute of Cellular Medicine, Child HealthUniversity of Newcastle upon TyneNewcastle upon TyneUK
  17. 17.Department of Paediatric RehabilitationChildren’s Memorial Health InstituteWarsawPoland
  18. 18.Department of Pediatrics and Developmental Disorders of Children and AdolescentsMedical University BialystokBiałystokPoland
  19. 19.Department of Pediatric HematologyOncology and BMT, Wroclaw Medical UniversityWroclawPoland
  20. 20.Department of Pediatric Hematology and Oncology, Collegium MedicumNicolaus Copernicus UniversityBydgoszczPoland
  21. 21.Department of Pediatric Hematology, Oncology and Haematopoietic Stem Cell TransplantationUniversity of Medical SciencesPoznańPoland
  22. 22.Department of Pediatric Hematology, Oncology and TransplantologyMedical UniversityLublinPoland
  23. 23.Department of OncologyChildren’s Memorial Health InstituteWarsawPoland
  24. 24.Centre of Chronic ImmunodeficiencyUniversity Medical Center Freiburg and University of FreiburgFreiburgGermany
  25. 25.Department of Pediatric Hematology/OncologyDr. von Hauner University Children’s HospitalMunichGermany

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