BCG-Related Immune Reconstitution Inflammatory Syndrome and Delayed Donor Chimerism After Allogeneic HSCT in T-B-NK+ SCID: A Successful Report of Steroid-Sparing Management.

BACKGROUND

Severe combined immunodeficiency (SCID) is a life-threatening disorder that requires early hematopoietic stem cell transplantation (HSCT). In regions where Bacillus Calmette-Guérin (BCG) vaccination is routinely administered at birth, disseminated BCG disease significantly complicates the clinical course in infants. Post-HSCT, immune reconstitution inflammatory syndrome (IRIS) poses an additional challenge, particularly in patients with active mycobacterial infections and mixed chimerism.

CASE PRESENTATION: We describe a female infant with T-B-NK+ SCID who developed disseminated BCG disease after routine BCG vaccination. At 6 months, she underwent HSCT from an HLA-matched sibling without a conditioning regimen, according to the EBMT/ESID guidelines for T-B-NK SCID. Donor chimerism was undetectable on two early occasions (days +14 and +28), initially raising concerns of graft failure. During this window, the patient developed paradoxical BCG-related IRIS, progressive lymphadenitis, and fever, which ultimately coincided with the first emergence of donor cells rather than graft loss. Corticosteroids were withheld because of the risk of infection and rejection. Instead, escalation of multidrug antimycobacterial therapy (intensified by adding amikacin and clarithromycin) led to clinical improvement. Subsequent testing demonstrated stable mixed donor chimerism (21% at +40, 23% at +60, and 51% at 8 months) with progressive donor T-cell reconstitution and the absence of graft-versus-host disease (GVHD). At the most recent follow-up, ~16 months after HSCT, the patient remained clinically well.

CONCLUSION

This case highlights the diagnostic and therapeutic dilemmas in managing SCID patients with BCG disease after HSCT. Early negative chimerism does not always predict graft failure, and paradoxical IRIS should be considered when clinical deterioration coincides with immune recovery after HSCT. Our findings suggest that conservative corticosteroid-sparing management with intensified antimycobacterial therapy may improve outcomes.