Geographical Distribution, Incidence, Malignancies, and Outcome of 136 Eastern Slavic Patients With Nijmegen Breakage Syndrome and NBN Founder Variant c.657_661del5.

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to lymphoid malignancies. The majority of NBS patients are identified with a homozygous five base pair deletion in the Nibrin (NBN) gene (c.657_661del5, p.K219fsX19) with a founder effect observed in Caucasian European populations, especially of Slavic origin. We present here an analysis of a cohort of 136 NBS patients of Eastern Slav origin across Belarus, Ukraine, Russia, and Latvia with a focus on understanding the geographic distribution, incidence of malignancy, and treatment outcomes of this cohort. Our analysis shows that Belarus had the highest prevalence of NBS (2.3 per 1,000,000), followed by Ukraine (1.3 per 1,000,000), and Russia (0.7 per 1,000,000). Of note, the highest concentration of NBS cases was observed in the western regions of Belarus and Ukraine, where NBS prevalence exceeds 20 cases per 1,000,000 people, suggesting the presence of an "Eastern Slavic NBS hot spot." The median age at diagnosis of this cohort ranged from 4 to 5 years, and delay in diagnosis was more pervasive in smaller cities and rural regions. A total of 62 (45%) patients developed malignancies, more commonly in males than females (55.2 vs. 34.2%; p=0.017). In 27 patients, NBS was diagnosed following the onset of malignancies (mean age: 8 years). Malignancies were mostly of lymphoid origin and predominantly non-Hodgkin lymphoma (NHL) (n=42, 68%); 38% of patients had diffuse large B-cell lymphoma. The 20-year overall survival rate of patients with malignancy was 24%. However, females with cancer experienced poorer event-free survival rates than males (16.6% vs. 46.8%, p=0.036). Of 136 NBS patients, 13 underwent hematopoietic stem cell transplantation (HSCT) with an overall survival of 3.5 years following treatment (range: 1 to 14 years). Indications for HSCT included malignancy (n=7) and immunodeficiency (n=6). Overall, 9% of patients in this cohort reached adulthood. Adult survivors reported diminished quality of life with significant physical and cognitive impairments. Our study highlights the need to improve timely diagnosis and clinical management of NBS among Eastern Slavs. Genetic counseling and screening should be offered to individuals with a family history of NBS, especially in hot spot regions.

Hodgkin's Lymphoma in Children and Adolescents: A Saint Petersburg Hodgkin's Lymphoma Group Study.

Purpose. Prospective analysis of the efficacy of the original protocol SPbHL-05 was performed. Patients and Methods. Sixty patients with Hodgkin's lymphoma (HL) aged less than 18 years old were treated in accordance with SPbHL-05 from January 2000, to July 2009. In induction chemotherapy we used VBVP and ABVD schedules followed by involved-field radiotherapy. Fourteen patients (23,3%) with 0-2 adverse factors (the favourable group) received two cycles of chemotherapy (VBVP), 25 children (41,7%) with 3-4 unfavorable signs (the intermediate group) received two cycles of VBVP alternating with two cycles of ABVD, 21 patient (35%) who had 5 or more adverse prognostic factors (the unfavourable group) received three cycles of VBVP alternating with three cycles of ABVD. Results. With a median follow-up of 68 months, overall survival (OS) at 5 years is 91.3%, event-free survival (EFS) is 82.8%. OS in the favourable and intermediate risk group were 100%, EFS were 92,9% and 90,7%, respectively, OS and EFS in unfavourable risk group-77,1% and 55,6%, respectively. Conclusion. The identification of prognostic risk factors and using medicines with less prominent side effects would be of major importance in the development of new strategies of treatment for childhood HL.