БЦЖ-ассоциированные осложнения у пациентов с первичными иммунодефицитами после аллогенной трансплантации гемопоэтических стволовых клеток

Abstract

BCG (Bacillus Calmette–Guerin) vaccine is widely used for the vaccination of newborns within the first few days of life to prevent mycobacterial infections. However, complications occurring after BCG vaccination in patients with primary immunodeficiencies (PIDs) can lead to serious consequences for their health and life. BCG vaccine-related complications occurring in patients with severe combined immunodeficiency (SCID) and chronic granulomatous disease (CGD) after hematopoietic stem cell transplantation (HSCT) constitute an important problem. The article presents a retrospective observational analysis of 45 patients with SCID and CGD who received BCG vaccination and underwent HSCT. In the post-transplant period, 33 (73.3%) patients had BCG-related complications, either localized or generalized. The presence of BCG vaccine-related complications in the pre-transplant period was a significant predictor of the development of post-transplant complications. The most severe and long-term BCG vaccine-related complications were observed in the patients with SCID: the median time to the resolution of symptoms of BCG infection was 30 days and 100 days in the CGD patients and the SCID patients, respectively (p< 0.001). The severity of BCG vaccine-related complications, the nature of the primary disease and the presence of pre-transplant BCG vaccine-related complications did not affect the overall survival (OS) of the patients: OS for the entire study group was 79.5 ± 6.6%. Non-compliance with antimycobacterial prophylaxis prior to HSCT resulted in severe infections in a number of patients. The treatment of BCG vaccine-related complications included a combination of several antimycobacterial agents, and anti-inflammatory drugs (such as glucocorticoids, interleukin-1 and 6 receptor antagonists) in cases of immune reconstitution inflammatory syndrome (n= 18). The only effective method of prophylaxis of BCG-related infections in patients with SCID and CGD in the pre- and post-transplant period is the exemption of newborns from BCG vaccination based on their family history. Uninterrupted antimycobacterial prophylaxis in vaccinated patients in the pre- and post-transplant period is also important. Furthermore, an effective uniform strategy for the prevention and treatment of BCG vaccine-related complications in PID patients both before and after HSCT is needed.