Update on VEXAS and role of allogeneic bone marrow transplant: Considerations on behalf of the Chronic Malignancies Working Party of the EBMT

• Published in: Bone marrow transplantation (Basingstoke) Vol. 57; no. 11; pp. 1642 - 1648
• Main Authors: Gurnari, Carmelo, McLornan, Donal P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2022; Nature Publishing Group
• Subjects: 692/699/1541; 692/699/1670; Algorithms; Anticoagulants; Bone marrow; Bone marrow transplantation; Cell Biology; Cytokines; Enzymes; Genotype & phenotype; Hematological diseases; Hematology; Hematopoietic stem cells; Internal Medicine; Malignancy; Medical prognosis; Medicine; Medicine & Public Health; Monoclonal gammopathy; Morbidity; Mortality; Mutation; Myelodysplastic syndrome; Myelodysplastic syndromes; Pathogenesis; Patients; Phenotypes; Progenitor cells; Proteins; Public Health; Review Article; Signs and symptoms; Stem cell transplantation; Stem Cells; Steroids; Thromboembolism; Thrombosis; Vacuoles
• ISSN: 0268-3369; 1476-5365; 1476-5365
• DOI: 10.1038/s41409-022-01774-8

VEXAS (acronym for Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a fascinating new entity encompassing a variety of clinical manifestations, spanning from auto-inflammatory symptoms to hematologic disorders, including myelodysplastic syndromes and plasma cell dyscrasias. Genetically defined by somatic mutations of the X-linked gene UBA1 in hematopoietic stem and progenitor cells, VEXAS typically manifests in males during the fifth/sixth decade of life. Since its discovery, several groups have documented pleomorphic clinical phenotypes, in addition to a plethora of therapeutic options ( e.g ., JAK inhibitors, hypomethylating agents, and allogeneic stem cell transplant, allo-HCT) in retrospective case series. However, no treatment guidelines have been validated to date, VEXAS patients are typically steroid-dependent and may manifest life-threatening inflammatory symptoms refractory to multiple lines of therapy. To date, the only curative option appears to be allo-HCT in suitable individuals. Nonetheless, this procedure carries an inherent risk of morbidity and mortality that must be judiciously evaluated against a phenotypically diverse disorder where the optimal therapeutic algorithm remains ill-defined. Herein, we provide an overview of the current VEXAS data/ therapeutic evidence and discuss the curative potential of allo-HCT whilst highlighting the efforts required for generation of robust data able to inform therapeutic decisions.