First successful allogeneic hematopoietic stem cell transplantation in STING-associated vasculopathy of infancy-A...

Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is a monogenic autoinflammatory disorder caused by gain-of-function mutations in TMEM173, leading to constitutive STING activation and persistent type I interferon signaling. Affected children develop early-onset cutaneous vasculopathy, systemic inflammation, and progressive interstitial lung disease, often refractory to standard immunosuppressive treatments. Janus kinase (JAK) inhibitors offer partial transient control, with risk of irreversible organ damage. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) could cure SAVI by replacing the mutant immune system, but experience is very limited. We report a 6-year-old boy with SAVI carrying the TMEM173 p.N154S mutation who failed multiple JAK inhibitors, including ruxolitinib, tofacitinib, and baricitinib and developed worsening lung fibrosis and cutaneous ulcers. He underwent allo-HSCT from a fully HLA-matched sibling after myeloablative conditioning. Engraftment was rapid. By 12 months post hematopoietic stem cell transplantation (HSCT), vasculitic skin lesions had healed, lung disease was stable, and inflammatory markers normalized, and cellular and humoral immunity reconstituted, including recovery of CD8⁺ central memory T cells and IgG and IgA. No graft-versus-host disease or major infections were observed. A transient autoimmune hemolytic anemia resolved with corticosteroids. This first successful SAVI allo-HSCT suggests curative potential via a durable immune reconstitution approach in selected patients with severe, treatment-refractory SAVI.