Successful allogeneic hematopoietic stem cell transplantation in patients with VEXAS syndrome: a 2-center experience

Abstract

The recently described vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is caused by somatic mutations in UBA1. Patients with VEXAS syndrome display late-onset autoinflammatory symptoms, usually refractory to treatment, and hematologic abnormalities. The identification of an easily-accessible specific marker (UBA1 mutations) is of particular interest as it allows the convergence of various inflammatory and hematological symptoms in a unique clinico-biological entity and gives the opportunity to design specific treatment strategies. Here we retrospectively identified 6 patients with VEXAS syndrome who underwent allogeneic hematopoietic stem cell transplantation (ASCT). To date, no treatment guidelines have been validated. In 4 patients, ASCT was guided by life-threatening autoinflammatory symptoms that were refractory to multiple therapies. Three patients are in durable complete remission 32, 38, and 37 months after ASCT. Two others are in complete remission response after 3 and 5 months. One unfortunately died post-ASCT. This report suggests that ASCT could be a curative option in patients with VEXAS syndrome and severe manifestations. Considering the complications and side effects of the procedure as well as the existence of other potential treatment, clinical trials are needed to define the subgroup of patients who will benefit from this strategy and its place in the therapeutic arsenal against VEXAS syndrome.

Figure 1.

Molecular and cytomorphologic diagnosis in patients with VEXAS syndrome. (A) The Sanger sequencing chromatograms for the UBA1 (NM_0033334) mutations: c.121 A>G, p.Met41Val (n = 2); c.121 A>C, p.Met41Leu (n = 1); c.122 T>C, p.Met41Thr (n = 1). (B) Characteristic vacuoles in erythroid and granulocytic precursor cells in BM from all UBA1-mutated patients (May-Grümwald-Giemsa stain). (C) Variant allele frequencies (VAFs) for putative somatic variants identified by high-throughput sequencing. Because of their location on the X chromosome, VAFs for UBA1 (black boxes) and ZRSR2 are divided by 2 to allow their representation on the same graph. UPN, unit patient number.