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, L. Máródi, Bernd H. Belohradsky, Peter Čižnár, Anna Shcherbina, Sara Sebnem Kilic, Ulrich Baumann, Markus G. Seidel, Andrew R. Gennery, Małgorzata Syczewska, Bożena Mikołuć & 9 others Krzysztof Kałwak, Jan Styczyński, Anna Pieczonka, Katarzyna Drabko, Anna Wakulińska, Benjamin Gathmann, Michael H. Albert, Urszula Skarżyńska, Ewa Bernatowska

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)538-549
Number of pages12
JournalJournal of Clinical Immunology
Volume35
Issue number6
DOIs
Publication statusPublished - Aug 14 2015

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Nijmegen Breakage Syndrome
Hematopoietic Stem Cell Transplantation
Neoplasms
Non-Hodgkin's Lymphoma
Survival
Respiratory Tract Infections
Cause of Death
Retrospective Studies
Databases

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Wolska-Kuśnierz, B., Gregorek, H., Chrzanowska, K., Piątosa, B., Pietrucha, B., Heropolitańska-Pliszka, E., ... Bernatowska, E. (2015). Nijmegen Breakage Syndrome: Clinical and Immunological Features, Long-Term Outcome and Treatment Options – a Retrospective Analysis. Journal of Clinical Immunology, 35(6), 538-549. https://doi.org/10.1007/s10875-015-0186-9

Nijmegen Breakage Syndrome : Clinical and Immunological Features, Long-Term Outcome and Treatment Options – a Retrospective Analysis. / Wolska-Kuśnierz, Beata; Gregorek, Hanna; Chrzanowska, Krystyna; Piątosa, Barbara; Pietrucha, Barbara; Heropolitańska-Pliszka, Edyta; Pac, Małgorzata; Klaudel-Dreszler, Maja; Kostyuchenko, Larysa; Pasic, Srdjan; Máródi, L.; Belohradsky, Bernd H.; Čižnár, Peter; Shcherbina, Anna; Kilic, Sara Sebnem; Baumann, Ulrich; Seidel, Markus G.; Gennery, Andrew R.; Syczewska, Małgorzata; Mikołuć, Bożena; Kałwak, Krzysztof; Styczyński, Jan; Pieczonka, Anna; Drabko, Katarzyna; Wakulińska, Anna; Gathmann, Benjamin; Albert, Michael H.; Skarżyńska, Urszula; Bernatowska, Ewa.

In: Journal of Clinical Immunology, Vol. 35, No. 6, 14.08.2015, p. 538-549.

Research output: Contribution to journalArticle

Wolska-Kuśnierz, B, Gregorek, H, Chrzanowska, K, Piątosa, B, Pietrucha, B, Heropolitańska-Pliszka, E, Pac, M, Klaudel-Dreszler, M, Kostyuchenko, L, Pasic, S, Máródi, L, Belohradsky, BH, Čižnár, P, Shcherbina, A, Kilic, SS, Baumann, U, Seidel, MG, Gennery, AR, Syczewska, M, Mikołuć, B, Kałwak, K, Styczyński, J, Pieczonka, A, Drabko, K, Wakulińska, A, Gathmann, B, Albert, MH, Skarżyńska, U & Bernatowska, E 2015, 'Nijmegen Breakage Syndrome: Clinical and Immunological Features, Long-Term Outcome and Treatment Options – a Retrospective Analysis', Journal of Clinical Immunology, vol. 35, no. 6, pp. 538-549. https://doi.org/10.1007/s10875-015-0186-9
Wolska-Kuśnierz B, Gregorek H, Chrzanowska K, Piątosa B, Pietrucha B, Heropolitańska-Pliszka E et al. Nijmegen Breakage Syndrome: Clinical and Immunological Features, Long-Term Outcome and Treatment Options – a Retrospective Analysis. Journal of Clinical Immunology. 2015 Aug 14;35(6):538-549. https://doi.org/10.1007/s10875-015-0186-9
Wolska-Kuśnierz, Beata ; Gregorek, Hanna ; Chrzanowska, Krystyna ; Piątosa, Barbara ; Pietrucha, Barbara ; Heropolitańska-Pliszka, Edyta ; Pac, Małgorzata ; Klaudel-Dreszler, Maja ; Kostyuchenko, Larysa ; Pasic, Srdjan ; Máródi, L. ; Belohradsky, Bernd H. ; Čižnár, Peter ; Shcherbina, Anna ; Kilic, Sara Sebnem ; Baumann, Ulrich ; Seidel, Markus G. ; Gennery, Andrew R. ; Syczewska, Małgorzata ; Mikołuć, Bożena ; Kałwak, Krzysztof ; Styczyński, Jan ; Pieczonka, Anna ; Drabko, Katarzyna ; Wakulińska, Anna ; Gathmann, Benjamin ; Albert, Michael H. ; Skarżyńska, Urszula ; Bernatowska, Ewa. / Nijmegen Breakage Syndrome : Clinical and Immunological Features, Long-Term Outcome and Treatment Options – a Retrospective Analysis. In: Journal of Clinical Immunology. 2015 ; Vol. 35, No. 6. pp. 538-549.
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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.",
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T2 - Clinical and Immunological Features, Long-Term Outcome and Treatment Options – a Retrospective Analysis

AU - Wolska-Kuśnierz, Beata

AU - Gregorek, Hanna

AU - Chrzanowska, Krystyna

AU - Piątosa, Barbara

AU - Pietrucha, Barbara

AU - Heropolitańska-Pliszka, Edyta

AU - Pac, Małgorzata

AU - Klaudel-Dreszler, Maja

AU - Kostyuchenko, Larysa

AU - Pasic, Srdjan

AU - Máródi, L.

AU - Belohradsky, Bernd H.

AU - Čižnár, Peter

AU - Shcherbina, Anna

AU - Kilic, Sara Sebnem

AU - Baumann, Ulrich

AU - Seidel, Markus G.

AU - Gennery, Andrew R.

AU - Syczewska, Małgorzata

AU - Mikołuć, Bożena

AU - Kałwak, Krzysztof

AU - Styczyński, Jan

AU - Pieczonka, Anna

AU - Drabko, Katarzyna

AU - Wakulińska, Anna

AU - Gathmann, Benjamin

AU - Albert, Michael H.

AU - Skarżyńska, Urszula

AU - Bernatowska, Ewa

PY - 2015/8/14

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N2 - 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.

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KW - non-Hodgkin’s lymphoma

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