Clinical Management of Severe Combined Immunodeficiencies

Severe combined immunodeficiency (SCID) is a category of inborn errors of immunity (IEI) characterized by the absence of both T and B lymphocytes function, resulting in life-threatening susceptibility to infections. The curative treatment for SCID is allogenic hematopoietic stem cells transplant (HSCT). An HLA-matched related donor is the preferred option for the transplant, with survival rates reaching up to 90%. Alternative options include matched unrelated donors, haploidentical parents, mismatched related donors, or cord blood donors. The latest guidelines recommend conditioning prior to HSCT, with the optimal conditioning strategy being tailored to each patient based on their specific genetic defect. Since the outcome of HSCT is strongly influenced by the patient’s age and infectious status, early diagnosis and a multidisciplinary approach are crucial to bridge these patients to transplant in the best possible condition. Infection prevention strategies, including antimicrobial prophylaxis against bacteria, viruses, and fungi, immunoglobulin replacement therapy, and strict isolation measures, must be implemented. While live attenuated vaccines are contraindicated, killed and microbial subcomponent vaccines can be safely administered. Gene therapy is also emerging as a safe alternative to allogeneic HSCT for specific genetic conditions causing SCID, such as Adenosine Deaminase Deficiency (ADA)-SCID.