Optimizing approaches to hematopoietic stem cell transplantation in children with Nijmegen breakage syndrome. A single-center experience

Introduction. Nijmegen breakage syndrome (NBS) belongs to a group of congenital disorders characterized by spontaneous chromosomal instability, immunodeficiency, predisposition to malignancies and increased sensitivity to specific DNA-damaging agents. The only curative treatment for patients with NBS is hematopoietic stem cell transplantation (HSCT) which is, however, associated with a high risk of endothelial toxicity and severe graft-versus-host disease. If previously HSCT was performed mainly in patients with oncologic complications, now recent statistical data and the implementation of neonatal screening support the necessity of early HSCT. A shift in the field of stem cell transplantation toward conditioning regimens aimed to reduce toxicity and risk of secondary malignancies may result in persistent mixed chimerism and insufficient antitumor effects in NBS patients with cancer. Currently, there are no standardized guidelines regarding the timing of HSCT, the selection of conditioning regimens or graft-versus-host disease prophylaxis in NBS. Aim: to demonstrate the evolution of HSCT approaches in children with NBS at a single center and to perform a retrospective analysis of therapeutic effectiveness with the assessment of long-term outcomes. Materials and methods. Over a 23-year period, 9 children with NBS underwent HSCT at the Russian Children’s Clinical Hospital. Results. The overall 10-year post-transplant survival rate was 0.67 (95% confidence interval 0.56–0.78). There were 3 transplant-related deaths. Most of the patients maintain mixed chimerism and require immunoglobulin replacement therapy. Conclusion. Taking into account the current trends and advances, HSCT approaches for NBS patients have been improved leading to better treatment outcomes. However, given the specific features of the disorder, further research is still needed to develop rational therapeutic strategies.