Extended Data Table 1 Clinical characteristics of the San Raffaele cohort of patients with VEXAS syndrome
From: Mechanisms of hematopoietic clonal dominance in VEXAS syndrome
- Between June 2021 and December 2023, 9 male patients (median age 71 years, range 66–84 years) were diagnosed with VEXAS syndrome after molecular genetic confirmation of mutation in the UBA1 gene exon 3 at San Raffaele Hospital (Milan, Italy). All patients were managed by a multidisciplinary team of hematologists and rheumatologists. The reasons for referral were either autoinflammatory signs and symptoms (including mainly fever, skin lesions and polychondritis) or progressive cytopenia (primarily macrocytic anemia). Mean diagnostic delay between symptom onset and/or laboratory abnormality detection subsequently attributed to VEXAS syndrome was 42 months (range 3–100 months). Identified UBA1 gene mutations were p.Met41Leu (n = 2), p.Met41Thr (n = 3), p.Met41Val (n = 3) and splice site c.118-1G ⟶ C (n = 1). All patients underwent next-generation sequencing for myeloid neoplasm mutations from the PB, which disclosed pathogenic or probably pathogenic somatic variants in two patients: one patient carried a single DNMT3A mutation, whereas the other had mutations in DNMT3A, ASXL1 and ZRSR2. At VEXAS syndrome diagnosis, five patients had already been diagnosed with MDS, whereas three patients developed MDS during the follow-up. All but one were already on steroid treatment at the first evaluation. In addition, six patients had already been treated with different combinations of immunosuppressive and disease-modifying drugs. A total of four patients was treated with erythropoietin; of these, two discontinued the treatment because of a loss of response. Vacuolization was found in BM cells in eight of nine patients. PT1 and PT6 died, respectively, at 35 and 10 months after diagnosis as a result of VEXAS-related complications.
- ILD, interstitial lung disease; DVT, deep vein thrombosis; ICUS, idiopathic cytopenia of undetermined significance; CCUS, clonal cytopenia of undetermined significance; MDS-LB, myelodysplastic neoplasia with low blasts; GC, glucocorticoids; CSA, ciclosporin A; Ruxo, ruxolitinib; CNK, nanakinumab; ANK, anakinra; MTX, methotrexate; Tofa, tofacitinib; AZT, azathioprine; LEN, lenalidomide; HCQ, hydroxycloroquine; TCZ, tocilizumab; AZA, 5-azacytidine; EPO, erythropoietin. ┼, only oncogenic and potentially oncogenic variants are reported.
