Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2021 Jan 15;27(2):575-584.
doi: 10.1158/1078-0432.CCR-20-2574. Epub 2020 Oct 20.

Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome

Beata Wolska-Kusnierz #  1 , Agata Pastorczak #  2 , Wojciech Fendler  3   4 , Anna Wakulinska  5 , Bozena Dembowska-Baginska  5 , Edyta Heropolitanska-Pliszka  1 , Barbara Piątosa  6 , Barbara Pietrucha  1 , Krzysztof Kałwak  7 , Marek Ussowicz  7 , Anna Pieczonka  8 , Katarzyna Drabko  9 , Monika Lejman  9 , Sylwia Koltan  10 , Jolanta Gozdzik  11 , Jan Styczynski  10 , Alina Fedorova  12 , Natalia Miakova  13 , Elena Deripapa  14 , Larysa Kostyuchenko  15 , Zdenka Krenova  16 , Eva Hlavackova  16   17 , Andrew R Gennery  18 , Karl-Walter Sykora  19 , Sujal Ghosh  20 , Michael H Albert  21 , Dmitry Balashov  22 , Mary Eapen  23 , Peter Svec  24 , Markus G Seidel  25 , Sara S Kilic  26 , Agnieszka Tomaszewska  27 , Ewa Wiesik-Szewczyk  28 , Alexandra Kreins  29 , Johann Greil  30 , Jochen Buechner  31 , Bendik Lund  32 , Hanna Gregorek  33 , Krystyna Chrzanowska #  34 , Wojciech Mlynarski #  35
Affiliations
Multicenter Study

Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome

Beata Wolska-Kusnierz et al. Clin Cancer Res. .

Abstract

Purpose: Nijmegen breakage syndrome (NBS) is a DNA repair disorder with a high predisposition to hematologic malignancies.

Experimental design: We describe the natural history of NBS, including cancer incidence, risk of death, and the potential effectiveness of hematopoietic stem cell transplantation (HSCT) in preventing both pathologies: malignancy and immunodeficiency.

Results: Among 241 patients with NBS enrolled in the study from 11 countries, 151 (63.0%) patients were diagnosed with cancer. Incidence rates for primary and secondary cancer, tumor characteristics, and risk factors affecting overall survival (OS) were estimated. The cumulative cancer incidence was 40.21% ± 3.5% and 77.78% ± 3.4% at 10 years and 20 years of follow-up, respectively. Most of the tumors n = 95 (62.9%) were non-Hodgkin lymphomas. Overall, 20 (13.2%) secondary malignancies occurred at a median age of 18 (interquartile range, 13.7-21.5) years. The probability of 20-year overall survival (OS) for the whole cohort was 44.6% ± 4.5%. Patients who developed cancer had a shorter 20-year OS than those without malignancy (29.6% vs. 86.2%; P < 10-5). A total of 49 patients with NBS underwent HSCT, including 14 patients transplanted before malignancy. Patients with NBS with diagnosed cancer who received HSCT had higher 20-year OS than those who did not (42.7% vs. 30.3%; P = 0.038, respectively). In the group of patients who underwent preemptive transplantation, only 1 patient developed cancer, which is 6.7 times lower as compared with nontransplanted patients [incidence rate ratio 0.149 (95% confidence interval, 0.138-0.162); P < 0.0001].

Conclusions: There is a beneficial effect of HSCT on the long-term survival of patients with NBS transplanted in their first complete remission of cancer.

PubMed Disclaimer

References

    1. Chrzanowska KH, Gregorek H, Dembowska-Bagińska B, Kalina MA, Digweed M. Nijmegen breakage syndrome (NBS). Orphanet J Rare Dis. 2012;7:13.
    1. Varon R VC, Platzer M, Cerosaletti KM, Chrzanowska KH, Saar K, Beckmann G, et al. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell. 1998;93:467–76.
    1. Varon R, Seemanova E, Chrzanowska K, Hnateyko O, Piekutowska-Abramczuk D, Krajewska-Walasek M, et al. Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations. Eur J Hum Genet. 2000;8:900–2.
    1. de Miranda NF, Björkman A, Pan-Hammarström Q. DNA repair: the link between primary immunodeficiency and cancer. Ann N Y Acad Sci. 2011;1246:50–63.
    1. 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. J Clin Immunol. 2015;35:538–49.

Publication types