Hematopoietic stem cell transplantation positively affects the natural history of cancer in Nijmegen breakage syndrome.

PURPOSE Nijmegen breakage syndrome (NBS) is a DNA repair disorder with a high predisposition to hematological 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 two hundred forty-one (n=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 (IQR, 13.7-21.5) years. The probability of 20-year overall 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). Forty-nine NBS patients underwent HSCT, including fourteen patients transplanted before malignancy. NBS patients 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). Among patients who underwent pre- emptive transplantation, only one patient developed cancer, which is 6.7 times lower as compared to non-transplanted patients (incidence rate ratio 0.149 (95% CI: 0.138-0.162), p<0.0001). CONCLUSIONS There is a beneficial effect of HSCT on the long-term survival of NBS patients transplanted in their first complete remission of cancer.