Purpose: Bacillus Calmette-Guerin (BCG) is a live attenuated vaccine with the potential of causing severe iatrogenic complications in patients with primary immunodeficiency diseases (PID) before and after hematopoietic stem cell transplantation (HSCT). We aim to investigate risk factors of post-HSCT BCG-related complications in PID patients.
Methods: A retrospective analysis of pediatric PID patients who had received the BCG vaccine and underwent HSCT at Hadassah-Hebrew University Medical Center, between 2007 and 2019.
Results: We found 15/36 (41.67%) patients who developed post-HSCT BCG-related complications. The most significant risk factor for developing BCG-related complications was T cell deficiency (47.6% of the non-complicated vs 83.3% of the BCGitis and 100% of the BCGosis groups had T cell lymphopenia, p = 0.013). None of the chronic granulomatous patients developed BCG-related manifestation post-transplant. Among T cell-deficient patients, lower NK (127 vs 698 cells/μl, p = 0.04) cell counts and NK-SCID were risk factors for ongoing post-HSCT BCGosis, as was pretransplant disseminated BCGosis (33.3% of patients with BCGosis vs none of the non-BCGosis patients, p = 0.04). Immune reconstitution inflammatory syndrome (IRIS) was observed in 3/5 patients with Omenn syndrome. Prophylactic antimycobacterial treatment was not proven effective.
Conclusion: BCG vaccination can cause significant morbidity and mortality in the post-transplant T cell-deficient patient, especially in the presence of pre-transplant disease. Taking a detailed medical history prior to administering, the BCG vaccine is crucial for prevention of this complication.
Keywords: BCG vaccination; hematopoietic stem cell transplantation; immune reconstitution inflammatory syndrome; primary immune deficiency; severe combined immunodeficiency.