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.

Belarusian Research Center for Pediatric Oncology and Hematology Minsk Belarus

Center for International Blood and Marrow Transplant Department of Medicine Medical College of Wisconsin Milwaukee Wisconsin

Department of Biostatistics and Translational Medicine Medical University of Lodz Lodz Poland

Department of Clinical Immunology and Allergology St Anne's University Hospital in Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Hematology Oncology and Internal Medicine Medical University of Warsaw Warsaw Poland

Department of Hematopoietic Stem Cell Transplantation Dmitriy Rogachev National Center for Pediatric Hematology Oncology and Immunology Moscow Russia

Department of Immunology and Hematopoietic Stem Cell Transplantation Federal Research Center for Pediatric Hematology Oncology and Immunology Moscow Russia

Department of Immunology Children's Memorial Health Institute Warsaw Poland

Department of Internal Medicine Pneumonology Allergology and Clinical Immunology Central Clinical Hospital of the Ministry of National Defense Military Institute of Medicine Warsaw Poland

Department of Medical Genetics The Children's Memorial Health Institute Warsaw Poland

Department of Microbiology and Clinical Immunology The Children's Memorial Health Institute Warsaw Poland

Department of Oncology Children's Memorial Health Institute Warsaw Poland

Department of Pediatric Hematology and Oncology Collegium Medicum Nicolaus Copernicus University Torun Bydgoszcz Poland

Department of Pediatric Hematology and Oncology Comenius University and National Institute of Children's Diseases Bratislava Slovakia

Department of Pediatric Hematology and Oncology Oslo University Hospital Oslo Norway

Department of Pediatric Hematology and Oncology University Hospital Heidelberg Germany

Department of Pediatric Hematology Oncology and Bone Marrow Transplantation Wroclaw Medical University Wroclaw Poland

Department of Pediatric Hematology Oncology and Transplantology Medical University of Lublin Poland

Department of Pediatric Immunology Western Ukrainian Specialized Children's Medical Centre Lviv Ukraine

Department of Pediatric Oncology and Hematology Federal Research Center for Pediatric Hematology Oncology and Immunology Moscow Russia

Department of Pediatric Oncology Hematology and Clinical Immunology Medical Faculty Center of Child and Adolescent Health Heinrich Heine University Düsseldorf Germany

Department of Pediatric Oncology Poznan University of Medical Sciences Poznan Poland

Department of Pediatric Oncology University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Pediatrics Hannover Medical School Hannover Germany

Department of Radiation Oncology Dana Farber Cancer Institute Boston Massachusetts

Department of Transplantation Institute of Pediatrics Jagiellonian University Medical College Krakow Poland

Department Pediatrics Oncology and Hematology Medical University of Lodz Lodz Poland

Dr von Hauner University Children's Hospital Ludwig Maximilians University Munich Germany

Great Ormond Street Hospital for Children NHS Foundation Trust London United Kingdom

Histocompatibility Laboratory Children's Memorial Health Institute Warsaw Poland

Pediatric Department St Olav University Hospital Trondheim Norway

Pediatric Immunology Division Department of Pediatrics Uludag University Medical Faculty Bursa Turkey

Research Unit Pediatric Hematology and Immunology Division of Pediatric Hematology Oncology Department of Pediatrics and Adolescent Medicine Medical University Graz Graz Austria

Translational and Clinical Research Institute Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle United Kingdom

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