Outcomes in Children with Primary Immunodeficiencies Undergoing HSCT Complicated By BCG-Osis

Introduction BCG vaccination is an important global health measure in countries with endemic tuberculosis but poses significant risks when administered to patients with Severe Combined Immune Deficiency (SCID) or genetic defects associated with Mendelian Susceptibility to Mycobacterial Diseases (MSMD). A study by Marciano et al. reported that BCG-osis occurred in over 50% of BCG-vaccinated patients with SCID. The impact of this infection on allogeneic hematopoietic stem cell transplant (HSCT) outcomes is unclear. Importantly, BCG-directed antimicrobial regimens are variable and little is known about whether these drugs impact engraftment when administered at the time of transplant. Methods Our study retrospectively reviewed transplant outcomes for children with primary immunodeficiencies (PIDs) complicated by BCG-osis between 2013 and 2019. Data analyzed include diagnosis, conditioning regimen, antimicrobial therapies, severity of BCG disease, survival and donor engraftment. Results 5 patients underwent allogeneic HSCT complicated by BCG-osis. Patient demographics and BCG treatment details are shown in Table 1. Patients received reduced intensity conditioning (RIC) with alemtuzumab/fludarabine/melphalan (n=3) or a reduced toxicity myeloablative conditioning (MAC) regimen with alemtuzumab/fludarabine/busulfan (n=2). All patients engrafted in less than 15 days with at least 99% whole blood donor chimerism. Two patients subsequently developed mixed chimerism. Both had SCID and received RIC. Whole blood donor chimerism for all patients is shown in Figure 1 and sorted T-cell donor chimerism for patients with mixed chimerism is shown in Figure 2. Four out of five patients (80%) remain alive at a median follow up of 894 days (range 92-2152 days). Conclusion Our experience suggests that children with PIDs undergoing HSCT complicated by BCG-osis have favorable outcomes with BCG-directed antimicrobial therapy. In addition, BCG-directed antimicrobial therapy was well tolerated and did not immediately appear to affect engraftment in our study. Patients who received MAC had durable donor chimerism. Expected mixed chimerism was observed in patients with SCID who received RIC, but donor T-cell chimerism was durable. As post-transplant BCG-osis occurred in several patients, our experience suggests that antimicrobial therapy is likely needed for several months until immune reconstitution is achieved.