Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Assessing the efficacy of allogeneic hematopoietic cell transplantation in VEXAS syndrome: results of a systematic review and meta-analysis

Bone Marrow Transplantation volume 59, pages 1423–1427 (2024) Cite this article

Subjects

Abstract

VEXAS syndrome is an X-linked monogenic disease with adult-onset inflammatory disease and myeloid dysplasia, with clinical presentation ensuing in the fifth decade of life or later. Inflammatory symptoms associated with VEXAS syndrome are treated with several lines of therapy, eventually requiring allogeneic hematopoietic cell transplantation (allo-HCT). No evidence from randomized controlled trials exists on allo-HCT versus other treatments in patients not responding to front-line therapy(ies). We show results of a systematic review/meta-analysis (SR/MA) following a search using EMBASE, PUBMED/MEDLINE and Web of Science on April 5, 2024. We extracted outcomes based on benefits (overall response rate (ORR), complete remission (CR), event-free survival (EFS) and overall survival (OS), and harms (non-relapse mortality (NRM) and acute and chronic graft-versus-host disease (GVHD)). The search identified 88 studies. Four studies (39 patients) met inclusion criteria. Median follow-up time after allo-HCT ranged from 8 to 18.5 months. Pooled EFS and OS rates were 56% and 86%, respectively. Pertaining to harms, pooled NRM rate was 14%. Pooled rates of acute and chronic GVHD were 42% and 13%, respectively. Allo-HCT is an effective treatment for VEXAS syndrome. We hope these results would increase awareness about this underdiagnosed and underreported disease.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
The alternative text for this image may have been generated using AI.
Fig. 2
The alternative text for this image may have been generated using AI.
Fig. 3
The alternative text for this image may have been generated using AI.
Fig. 4
The alternative text for this image may have been generated using AI.

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this published article.

References

  1. Beck DB, Ferrada MA, Sikora KA, Ombrello AK, Collins JC, Pei W, et al. Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. N Engl J Med. 2020;383:2628–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Grayson PC, Patel BA, Young NS. VEXAS syndrome. Blood. 2021;137:3591–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Poulter JA, Collins JC, Cargo C, De Tute RM, Evans P, Ospina Cardona D, et al. Novel somatic mutations in UBA1 as a cause of VEXAS syndrome. Blood. 2021;137:3676–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Obiorah IE, Patel BA, Groarke EM, Wang W, Trick M, Ombrello AK, et al. Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1. Blood Adv. 2021;5:3203–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bourbon E, Heiblig M, Gerfaud Valentin M, Barba T, Durel CA, Lega JC, et al. Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood. 2021;137:3682–4.

    Article  CAS  PubMed  Google Scholar 

  6. Gurnari C, Pagliuca S, Durkin L, Terkawi L, Awada H, Kongkiatkamon S, et al. Vacuolization of hematopoietic precursors: an enigma with multiple etiologies. Blood. 2021;137:3685–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Vitale A, Caggiano V, Martin-Nares E, Frassi M, Dagna L, Hissaria P, et al. Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry. Semin Arthritis Rheum. 2024;66:152430.

    Article  CAS  PubMed  Google Scholar 

  8. Casal Moura M, Baqir M, Tandon YK, Samec MJ, Hines AS, Reichard KK, et al. Pulmonary manifestations in VEXAS syndrome. Respir Med. 2023;213:107245.

    Article  PubMed  Google Scholar 

  9. Mekinian A, Zhao LP, Chevret S, Desseaux K, Pascal L, Comont T, et al. A Phase II prospective trial of azacitidine in steroid-dependent or refractory systemic autoimmune/inflammatory disorders and VEXAS syndrome associated with MDS and CMML. Leukemia. 2022;36:2739–42.

    Article  PubMed  Google Scholar 

  10. Raaijmakers M, Hermans M, Aalbers A, Rijken M, Dalm V, van Daele P, et al. Azacytidine Treatment for VEXAS Syndrome. Hemasphere. 2021;5:e661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sockel K, Gotze K, Ganster C, Bill M, Georgi JA, Balaian E, et al. VEXAS syndrome: complete molecular remission after hypomethylating therapy. Ann Hematol. 2024;103:993–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Heiblig M, Ferrada MA, Koster MJ, Barba T, Gerfaud-Valentin M, Mekinian A, et al. Ruxolitinib is more effective than other JAK inhibitors to treat VEXAS syndrome: a retrospective multicenter study. Blood. 2022;140:927–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Loschi M, Roux C, Sudaka I, Ferrero-Vacher C, Marceau-Renaut A, Duployez N, et al. Allogeneic stem cell transplantation as a curative therapeutic approach for VEXAS syndrome: a case report. Bone Marrow Transpl. 2022;57:315–8.

    Article  Google Scholar 

  14. Al-Hakim A, Poulter JA, Mahmoud D, Rose AMS, Elcombe S, Lachmann H, et al. Allogeneic haematopoietic stem cell transplantation for VEXAS syndrome: UK experience. Br J Haematol. 2022;199:777–81.

    Article  PubMed  Google Scholar 

  15. Diarra A, Duployez N, Fournier E, Preudhomme C, Coiteux V, Magro L, et al. Successful allogeneic hematopoietic stem cell transplantation in patients with VEXAS syndrome: a 2-center experience. Blood Adv. 2022;6:998–1003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gurnari C, Koster L, Baaij L, Heiblig M, Yakoub-Agha I, Collin M, et al. Allogeneic hematopoietic cell transplantation for VEXAS syndrome: results of a multicenter study of the EBMT. Blood Adv. 2024;8:1444–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Mangaonkar A, Langer KJ, Lasho T, Finke C, Litzow MR, Hogan WJ, et al. Pilot Prospective Study of Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Vexas Syndrome. Transplant Cell Ther. 2024;30:S292.

    Article  Google Scholar 

  18. Wells GASB, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses Ontario, Canada. 2024. Available from: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

  19. StataCorp. 18.5 ed. Texas, USA: StataCorp LLC; 2023.

  20. Deeks J, Higgins J, Altman D. Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JPTTJ, Chandler J, Cumpston M, Li T, Page MJ, Welch VA editors. Cochrane Handbook for Systematic Reviews of Interventions, version 6.4 (updated August 2023). United Kingdom: Cochrane, 2023.

  21. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology-Oncology and O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA

    Razan Mohty & Omer Jamy

  2. Research Methodology and Biostatistics Core, Office of Research Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    Tea Reljic & Ambuj Kumar

  3. Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program and Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL, USA

    Nayef Abdel-Razeq, Talha Badar & Mohamed A. Kharfan-Dabaja

  4. King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

    Mahmoud Aljurf

Authors
  1. Razan Mohty
    View author publications

    Search author on:PubMed Google Scholar

  2. Tea Reljic
    View author publications

    Search author on:PubMed Google Scholar

  3. Nayef Abdel-Razeq
    View author publications

    Search author on:PubMed Google Scholar

  4. Omer Jamy
    View author publications

    Search author on:PubMed Google Scholar

  5. Talha Badar
    View author publications

    Search author on:PubMed Google Scholar

  6. Ambuj Kumar
    View author publications

    Search author on:PubMed Google Scholar

  7. Mahmoud Aljurf
    View author publications

    Search author on:PubMed Google Scholar

  8. Mohamed A. Kharfan-Dabaja
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Study concept: RM, TR, AK, and MAK-D. Study design: RM, TR, NA-R, AK, MA, MAK-D. Data collection: RM, TR, NA-R, AK, MAK-D. Statistical analysis: TR and AK. Interpretation of results: RM, TR, NA-R, OJ, TB, AK, MA, MAK-D. Manuscript writing: RM, TR, NA-R, OJ, TB, AK, MA, MAK-D.

Corresponding author

Correspondence to Mohamed A. Kharfan-Dabaja.

Ethics declarations

Competing interests

RM, TR, NA-R, TB, AK and MA report no relevant conflicts of interest. OJ reports advisory board participation for Ascentage pharma. MAK-D reports research/grant support from Bristol Myers Squibb, Novartis and Pharmacyclics; Lecture/Honoraria from Kite Pharma.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohty, R., Reljic, T., Abdel-Razeq, N. et al. Assessing the efficacy of allogeneic hematopoietic cell transplantation in VEXAS syndrome: results of a systematic review and meta-analysis. Bone Marrow Transplant 59, 1423–1427 (2024). https://doi.org/10.1038/s41409-024-02375-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41409-024-02375-3

This article is cited by

Search

Advanced search

Quick links