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

Abstract

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.

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Fig. 1: Vacuoles of hematopoietic precursors in a patient with VEXAS syndrome and MDS-MLD.
Fig. 2: Diagnostic algorithm of VEXAS.
Fig. 3: Patient, disease-specific and treatment-related factors influencing the allo-HCT decision-making process in VEXAS.

Data availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

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Acknowledgements

This work was supported by a grant from the Edward P. Evans Foundation (to CG). The Authors thank Dr. Heesun J. Rogers for providing histopathology pictures.

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CG and DPM conceived the idea and wrote the manuscript.

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Correspondence to Donal P. McLornan.

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Gurnari, C., McLornan, D.P. Update on VEXAS and role of allogeneic bone marrow transplant: Considerations on behalf of the Chronic Malignancies Working Party of the EBMT. Bone Marrow Transplant (2022). https://doi.org/10.1038/s41409-022-01774-8

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