Allogenic haematopoietic stem cell transplantation in VEXAS: A review of 33 patients.

Vacuolation, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a multisystem disease due to a genetic mutation in the ubiquitin-activating enzyme (UBA1). Allogeneic haematopoietic stem cell transplantation (allo-HSCT) offers both therapeutic and cure but also carries significant risks. A review of VEXAS and HSCT cases was undertaken. Thirty-three patients were identified; majority males (n = 32, 97.0%), median time from symptoms to HSCT: 3 years (IQR 2.0-4.8) and median age of 59 years (IQR 52.5-65.5). UBA1 mutation Met41Thr was most common (11/32, 34.4%). The median variant allele frequency was 56.5% (IQR 43.0-73.5) with no correlation with increasing age. Prior to HSCT, 4.5 (IQR 2.8-6) treatments were trialled. Peripheral blood HSCT (30/31, 96.8%) and HLA-matched, unrelated donor (18/32, 56.3%) were most common. Conditioning regimens varied, with reduced intensity treatment with fludarabine as a co-agent most frequently administered (12/31, 38.7%). Both acute and/or chronic GVHD (18/32, 56.3%) and infections were common (12/32, 37.5%). Overall, 27 individuals (81.8%) were alive, and those undergoing HSCT prospectively had median follow up of 9 months (IQR 3.8-14.4). Of the six deceased, infection was implicated in four. In 11 cases with post-HSCT molecular data, a complete eradication of UBA1 mutation was reported. In summary, while consensus treatment strategy regarding VEXAS is lacking, this review highlights HSCT may remain not only a therapeutic option but also enable cure. However, considerations regarding comorbidities, concurrent haematological disorders as well as overall risks of GVHD and infections need to be made. Key points • Very few reported prospective cases of VEXAS and allogeneic haematopoietic stem cell transplantation (allo-HSCT) have been reported. • While risks of graft versus host disease and infection remain barriers, this treatment modality remains an option for selected patients. • Allo-HSCT is the only treatment strategy which can remove the UBA1 mutation.