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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

Bone Marrow Transplantation volume 57, pages 1642–1648 (2022)Cite this article

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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.

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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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Authors and Affiliations

  1. Translational Hematology and Oncology Research Department, Taussig Cancer Center, Cleveland Clinic, Cleveland, USA

    Carmelo Gurnari

  2. Department of Biomedicine and Prevention, PhD in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy

    Carmelo Gurnari

  3. Department of Stem Cell Transplantation and Haematology, University College London Hospitals, London, UK

    Donal P. McLornan

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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 57, 1642–1648 (2022). https://doi.org/10.1038/s41409-022-01774-8

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