Jean‐Baptiste Rieu

Supplemental Table 1. Characteristics of AML patients. Supplemental Table 2. Flow cytometry antibodies. Supplemental Table 3. Multivariate Cox regression analysis of factors contributing to overall survival of AML patients. Supplemental Table 4. Multivariate Cox regression analysis of factors contributing to leukemia free survival of AML patients. Supplemental Table 5. Multivariate Cox regression analysis of factors contributing to overall survival of AML patients including the association of bulk and LSC MRD parameters. Supplemental Table 6. Multivariate Cox regression analysis of factors contributing to leukemia free survival of AML patients including the association of bulk and LSC MRD parameters.

Supplemental figure 1. Flow chart for sample availability of patients included in our study and their outcome. Supplemental figure 2. Supplemental figure 3. Size of LSC nodes in CD34+CD38- subpopulation in AML-CD34+ and AMLCD34- populations. Mann-Whitney test. Supplemental figure 4. LSC phenotypic profiles according to MRD status. Normalized MFI of CD34, CD38, CD45RA, CD135 and CD133 in LSC nodes used to measure LSC MRD. Mann-Whitney tests. Supplemental figure 5. Landmark analysis at 6 months of the impact of HSCT according to MRD status. Supplemental figure 6. Evaluation of immunophenotypic markers in chemoresistant and chemosensitive AML patients at diagnosis. Supplemental figure 7. Evaluation of LSC phenotypic markers in clinically relevant AML patients in relation to Figure 4.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a severe monogenic disorder caused by somatic mutations in ubiquitin-like modifier activating enzyme 1 (UBA1), characterized by inflammation, cytopenias, and frequent association with myelodysplastic neoplasms (MDS). Steroid dependence is common, and targeted therapies have demonstrated limited efficacy. Azacitidine (AZA), a hypomethylating agent used in MDS, has shown potential in VEXAS syndrome but data remain limited. This multicenter retrospective study assessed AZA efficacy and safety in 88 patients with genetically confirmed VEXAS syndrome from FRENVEX (French VEXAS study group), 80% meeting World Health Organization 2022 MDS criteria. Inflammatory response rates were 41% at 6 months and 54% at 12 months, regardless of MDS status. A total of 50 (61%) patients achieved inflammatory response, with 70% occurring at 6 months, suggesting a delayed median response. Among responders, relapse-free survival on AZA was 90% at 1 year and 85% at 5 years. Of the 12 responders who discontinued AZA, 9 relapsed after a median of 3.1 years (range, 0.4-5.6), with effective reexposure in 4 of 5 patients. Hematological responses included red blood cell transfusion independence in 65% and platelet improvement in 77% of patients. Molecular response, defined as a ≥25% reduction in UBA1 variant allele frequency (VAF), was observed in 65% of patients, all of whom achieved inflammatory and hematological responses; and VAF dropped to <2% in 43% of cases. Infections (34%) and cytopenias (36%) were common, particularly during the first 3 cycles. This study establishes AZA as an effective therapy for VEXAS syndrome, improving inflammation, cytopenias, and UBA1 clonal burden, warranting larger prospective trials.

Durable responses with front-line rituximab in autoimmune cytopenias associated with indolent B-Cell clones.