BCG disease in SCID: three decades of experience in a pediatric transplant center

Severe combined immunodeficiency (SCID) patients are highly susceptible to complications following Bacille Calmette-Guérin (BCG) vaccination, yet management of BCG disease during hematopoietic stem cell transplantation (HSCT) remains challenging. This retrospective study analyzed 36 SCID patients with documented BCG vaccination who underwent HSCT at the University Medical Center Ulm between 1983 and 2014, and incorporated data from 15 international centers. Disseminated BCG disease occurred in 64% of patients, and mortality was 28%, with two deaths directly related to BCG complications. The Copenhagen 1331 vaccine strain was associated with longer remission times compared to other strains. Early initiation of multidrug tuberculostatic therapy—preferably more than six weeks before HSCT—correlated with improved outcomes at one year post-transplant. Exacerbations of BCG disease were frequent following HSCT, particularly during immune reconstitution, resembling immune reconstitution inflammatory syndrome. Overall, 75% of patients achieved remission, and locoregional disease resolved significantly earlier than disseminated infection. These findings underscore the importance of early SCID diagnosis, prompt initiation of combination antimycobacterial therapy, and timely HSCT to improve prognosis. Delaying routine BCG vaccination until newborn T-cell screening can prevent severe complications in undiagnosed SCID infants.