Hypomethylating agents for patients with VEXAS without myelodysplastic syndrome: Clinical outcome and longitudinal follow‐up of vacuolization and UBA1 clonal dynamics

British Journal of Haematology, Год журнала: 2025, Номер 206(2), С. 565 - 575

Опубликована: Янв. 13, 2025

VEXAS syndrome is a haemato-inflammatory disease caused by somatic UBA1 mutations and characterized cytoplasmic vacuoles in myeloid erythroid precursor cells. Although there currently no standard treatment algorithm for VEXAS, patients are generally treated with anti-inflammatory therapies focused on symptom management, only partial effectiveness. Hypomethylating agents (HMA) have shown promise concomitant myelodysplastic (MDS), while the efficacy of HMA without MDS largely unknown. Furthermore, usefulness monitoring variant allele frequency (VAF) or vacuolization cells over course has not been extensively investigated. We evaluated four performed longitudinal analyses VAF during treatment. led to overall clinical improvement, dramatic reduction UBA1, normalization haematological inflammatory markers quantifiable decrease vacuolization, leading us speculate that unlike therapies, may well act as disease-modifying If these findings confirmed further studies, it could lead early use all patients-with MDS.

Язык: Английский

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Case report: VEXAS syndrome: an atypical indolent presentation as sacroiliitis with molecular response to azacitidine

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Май 22, 2024

VEXAS syndrome is a recently described autoinflammatory caused by the somatic acquisition of UBA1 mutations in myeloid precursors and frequently associated with hematologic malignancies, chiefly myelodysplastic syndromes. Disease presentation can mimic several rheumatologic disorders, delaying diagnosis. We describe case atypical resembling late-onset axial spondylarthritis, later progressing to systemic inflammatory chondritis, cutaneous vasculitis, transfusion-dependent anemia, requiring high doses steroids. Ruxolitinib was used as first steroid-sparing strategy without response. However, azacitidine showed activity controlling both inflammation mutant clone. This raises question whether azacitidine’s anti-inflammatory effects are dependent on or independent clonal control. discuss potential relevance molecular remission highlight importance multidisciplinary team for care such complex patients.

Язык: Английский

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

Bone Marrow Transplantation, Год журнала: 2024, Номер 59(10), С. 1423 - 1427

Опубликована: Июль 26, 2024

Язык: Английский

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VEXAS Syndrome: A Comprehensive Review of Current Therapeutic Strategies and Emerging Treatments

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(22), С. 6970 - 6970

Опубликована: Ноя. 19, 2024

VEXAS syndrome is a recently identified autoinflammatory disorder resulting from somatic mutations in the UBA1 gene, leading to complex spectrum of severe inflammatory and hematologic manifestations. The absence established treatment guidelines variability clinical presentation make its management particularly challenging. Current therapeutic approaches are often based on limited evidence, their effectiveness remains inconsistent. This review seeks consolidate existing knowledge strategies for syndrome, offering critical evaluation efficacy addressing gaps current literature. As recognition grows, there an urgent need explore more targeted, effective treatments that can address both aspects disease. By providing comprehensive analysis landscape, this aims guide clinicians researchers toward developing effective, long-term life-threatening condition.

Язык: Английский

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VEXAS, Chediak–Higashi syndrome and Danon disease: myeloid cell endo-lysosomal pathway dysfunction as a common denominator?

Cellular & Molecular Biology Letters, Год журнала: 2025, Номер 30(1)

Опубликована: Янв. 26, 2025

Abstract Vacuolization of hematopoietic precursors cells is a common future several otherwise non-related clinical settings such as VEXAS, Chediak–Higashi syndrome and Danon disease. Although these disorders have priori nothing to do with one other from point view, all share abnormal vacuolization in different cell types including the erythroid/myeloid lineage that likely consequence moderate drastic dysfunctions ubiquitin proteasome system and/or endo-lysosomal pathway. Indeed, genes affected three diseases UBA1, LYST or LAMP2 are known be direct indirect regulators lysosome trafficking function modes autophagy. Furthermore, highly expressed more mature myeloid pointing out their important cells. deficiency for instance associated alterations architecture function. It thus well established disease patients harbor invalidating mutations exhibit giant lysosomes containing undigested materials characteristic defects fusion autophagosomes, feature also found VEXAS CHS. Other similarities regarding include granulocyte monocyte recurrent inflammatory climate. In present review we discuss possibility some manifestations diseases, notably ones consecutive dysfunction pathway myeloid/erythroid progenitors neutrophiles, monocytes macrophages. Finally, propose reacidification way reinducing functionalities autophagy potential approach better management diseases.

Язык: Английский

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Myeloid neoplasm inspired intensive therapy in VEXAS syndrome: A single‐centre experience

British Journal of Haematology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Summary There is still no standard of care and unmet medical needs in refractory/advanced VEXAS (vacuoles myeloid progenitors, E1 ubiquitin activating enzyme, X‐linked, autoinflammatory manifestations somatic) syndrome with or without associated haematological neoplasm. We report the clinical outcome four multirefractory/advanced patients treated acute leukaemia‐like therapeutic approaches. All responded to inflammatory/haematological VEXAS‐related features, which were measurable residual disease response (partial complete). Prospective studies evaluating new effective strategies order reduce clonal burden are warranted.

Язык: Английский

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VEXAS syndrome: A newly identified X-Linked hematoinflammatory disorder – A comprehensive overview of its genetic, molecular, inflammatory, and clinical landscape

Journal of Autoimmunity, Год журнала: 2025, Номер 154, С. 103425 - 103425

Опубликована: Апрель 29, 2025

Язык: Английский

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Clonal hematopoiesis meets an autoinflammatory disease: the new paradigm of VEXAS syndrome

Expert Review of Hematology, Год журнала: 2025, Номер unknown

Опубликована: Май 21, 2025

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an acquired autoinflammatory disorder caused by somatic mutations in the UBA1 gene. Predominantly affecting males over 50, disease presents with systemic inflammation, hematologic abnormalities, and features of clonal hematopoiesis, nearly half patients developing myelodysplastic syndromes (MDS). The interaction between inflammation expansion defines progression, emphasizing need for a comprehensive understanding its pathogenesis management. This review discusses clinical spectrum, genetic landscape, pathogenic mechanisms syndrome. correlation severity explored, alongside role hematopoiesis inflammatory pathways. Current treatments, including corticosteroids, immunosuppressants, JAK inhibitors, azacitidine, are evaluated efficacy limitations. potential allogeneic hematopoietic stem cell transplantation (allo-HSCT) as curative approach also addressed. Literature search was conducted from January 2020 to present using PubMed Scopus databases identify relevant studies. reflects complex autoinflammation hematopoiesis. While targeted therapies offer symptomatic control, responses remain variable. Future strategies should focus on genotype-driven, personalized treatments optimizing allo-HSCT protocols improve patient outcomes disease-modifying potential.

Язык: Английский

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Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: A comprehensive review of cases across different ethnicities

European Journal of Internal Medicine, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) is an autoinflammatory disease associated with mutations in the UBA1 gene. Although has been described many different countries, no studies have investigated origin of patients to determine if universal across ancestries. The aim this study investigate distribution VEXAS syndrome continents and ethnicities. A literature review all reported cases was conducted between October 2020 April 2025 using term 'VEXAS' all-field filter Pubmed Web Science databases. Epidemiological clinical data were collected for included patients. If country not described, it assumed be same as evaluation. subgroup analysis performed whose or ethnicity documented by authors. 674 collected, from four 32 countries. Considering origin, 451 19 Of these, recorded 372 presence Caucasian, Central East Asian, South Middle Eastern, American results support a broad global highlight importance investigating regardless patient's compatible symptoms.

Язык: Английский

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Case report: VEXAS syndrome with excellent response to treatment with azacitidine

Annals of Hematology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 16, 2024

Язык: Английский

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