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

Abstract

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.