Allogeneic hematopoietic stem cell transplantation for VEXAS syndrome: A review and a case report

Background VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by somatic UBA1 mutations and frequently complicated by myelodysplastic syndrome (MDS). Conventional immunosuppressive and anti-inflammatory therapies are often ineffective, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment, although its optimal timing and donor selection remain uncertain. Case Presentation A 67-year-old man with VEXAS syndrome and MDS harboring UBA1 (p.M41T) and EZH2 mutations, refractory to azacitidine and corticosteroids, successfully underwent allo-HSCT from a one-antigen–mismatched related donor. Post-transplant chronic graft-versus-host disease was well controlled with ruxolitinib. Methods and Results We reviewed eight studies comprising 45 allo-HSCT recipients with VEXAS syndrome. The median age at transplantation was 59 years, and patients had received a median of five prior systemic therapies. MDS was present in 53.3% of cases, while 42.2% underwent transplantation for VEXAS without overt hematologic malignancy. The most frequent UBA1 variant was p.Met41Val (37.8%). At last follow-up, 84.4% of patients were alive, with resolution of inflammatory manifestations in most cases. Conclusion Allo-HSCT represents a curative option for refractory VEXAS syndrome. Comprehensive genetic profiling may aid in identifying candidates for early transplantation. If early transplantation is required, human leukocyte antigen-mismatched donors may be selected.