Allogeneic hematopoietic cell transplantation for VEXAS syndrome: results of a multicenter study of the EBMT

Blood Advances, Journal Year: 2024, Volume and Issue: 8(6), P. 1444 - 1448

Published: Feb. 8, 2024

Language: Английский

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Molecular and clinical presentation of UBA1-mutated myelodysplastic syndromes

Blood, Journal Year: 2024, Volume and Issue: 144(11), P. 1221 - 1229

Published: April 30, 2024

Language: Английский

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VEXAS syndrome: complete molecular remission after hypomethylating therapy

Annals of Hematology, Journal Year: 2024, Volume and Issue: 103(3), P. 993 - 997

Published: Jan. 12, 2024

Abstract The VEXAS syndrome, a genetically defined autoimmune disease, associated with various hematological neoplasms has been attracting growing attention since its initial description in 2020. While therapeutic strategies have explored case studies, the optimal treatment strategy is still under investigation and allogeneic cell transplantation considered only curative treatment. Here, we describe 2 patients who achieved complete molecular remission of underlying UBA1 mutant clone outside context HCT. Both received hypomethylating agent azacitidine, deep triggered de-escalation even cessation sustained one them. Prospective studies are necessary to clarify which will benefit most from therapy understand variability response different strategies.

Language: Английский

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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, Journal Year: 2025, Volume and Issue: 206(2), P. 565 - 575

Published: Jan. 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.

Language: Английский

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Efficacy and safety profile of biotechnological agents and Janus kinase inhibitors in VEXAS syndrome: data from the international AIDA Network VEXAS registry

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 19, 2025

VEXAS syndrome, a recently identified systemic autoinflammatory disorder, poses new diagnostic and management challenges. Based on experience with other diseases, anti-interleukin (IL)-1, anti-IL-6, anti-tumor necrosis factor (TNF) biotechnological agents, Janus kinase inhibitors (JAKis) have been widely employed in patients. The aim of this study is to evaluate the global effectiveness safety agents JAKis using data from real-world context. Clinical, laboratory, therapeutic patients were obtained international AIDA Network registry. In total, 69 enrolled study. Among them, 12 (13 treatment courses) received IL-1 inhibitors, administered anti-IL-6 8 (9 treated anti-TNF 16 (17 JAKis. A complete response was observed 3 (23%) anti-IL-1 2 (15%) receiving IL-6 1 patient (11%) TNF 4 (23.5%) mean prednisone (or equivalent) dosage significantly decreased during (p = 0.01), while glucocorticoids changed anti-TNF, JAKi non-significant fashion. total 21 experienced adverse events, which led death (gut perforation, Legionnaires' disease, infectious pneumonia) JAKis; withdrawal required for out along JAKis, represent promising options patients, albeit careful monitoring mandatory control disease activity ensure safety.

Language: Английский

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Latest Insights and Therapeutic Advances in Myelodysplastic Neoplasms

Cancers, Journal Year: 2024, Volume and Issue: 16(8), P. 1563 - 1563

Published: April 19, 2024

Myelodysplastic syndromes/neoplasms (MDSs) encompass a range of hematopoietic malignancies, commonly affecting elderly individuals. Molecular alterations in the stem cell compartment drive disease pathogenesis. Recent advancements genomic profiling have provided valuable insights into biological underpinnings MDSs and expanded therapeutic options, particularly for specific molecularly defined subgroups. This review highlights diagnostic principles, classification updates, prognostic stratification systems, novel treatments, which could inform future clinical trials enhance management adult MDS patients,

Language: Английский

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VEXAS syndrome: is it more a matter of inflammation or hematopoietic clonality? A case series approach to diagnosis, therapeutic strategies and transplant management

Annals of Hematology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Abstract VEXAS syndrome is a complex hemato-inflammatory disorder, driven by somatic mutations in the UBA1 gene within hematopoietic precursor cells. It characterized systemic inflammation, rheumatological manifestations, and frequent association with myelodysplastic (MDS). We present series of four cases, all which include concomitant MDS, each displaying distinct genetic signatures clinical features at diagnosis, focus on their diagnostic therapeutic implications. Our findings underscore importance extending sequencing beyond exon 3 cases strong suspicion. Given rarity non-canonical variants limited annotation, germline tissue control should be considered to differentiate from mutations. Hematological management, including considerations for transplantation, was primarily guided Revised International Prognostic Scoring System (IPSS-R) MDS due absence specific risk stratification system or therapy guidelines. A critical point our discussion role inflammation peri-transplant period; one patient, combination disease-modifying antirheumatic drugs (DMARDs) high-dose corticosteroids before transplant crucial controlling resulting successful stem cell transplantation (HSCT). In contrast, uncontrolled contributed death another patient. These highlight effective management optimizing HSCT outcomes. Additionally, study emphasizes urgent need guidelines syndrome, comprehensive optimal timing transplantation.

Language: Английский

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Efficacy and safety of conventional disease-modifying antirheumatic drugs in VEXAS syndrome: real-world data from the international AIDA network

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 7, 2025

Background VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset autoinflammatory condition resulting in severe, often treatment-refractory inflammation. Currently, there are no established treatment guidelines for syndrome. Objectives To assess the efficacy and safety of conventional disease-modifying antirheumatic drugs (cDMARDs) a cohort patients. Methods Data from patients were obtained International AIDA Network registry. Results 36 evaluated, with 28 (77.8%) treated cDMARDs as monotherapy - concomitant glucocorticoids (GC) 8 (22.2%) receiving combination different plus GC. Complete response (CR), partial (PR), failure to reported 4/22 (18.2%), 11/22 (50%), 7/22 (31.8%) courses, respectively. All GCs at start cDMARD monotherapy, GC discontinuation was observed later. No significant differences dosage 3-month ( p = 0.43), 6-month 0.31), 12-month 0.21) visits. Conversely, sparing resulted be statistically when using methotrexate 0.02). As combinations, cases achieved CR, while PR 5/9 (55.6%). Seventeen adverse events reported, seven which led discontinuation. Conclusion Many report benefit cDMARDs, smaller yet not negligible number exhibit CR; remain viable option this disorder, especially initial low need steroid-sparing effect immediately urgent.

Language: Английский

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Clinical features and treatments of VEXAS syndrome in critical care: a scoping review

Critical Care, Journal Year: 2025, Volume and Issue: 29(1)

Published: April 17, 2025

Abstract Background Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently discovered severe disorder that predominantly affects adult males, characterized by systemic inflammation and hematologic abnormalities. Despite its profound impact on patient outcomes, awareness of VEXAS among critical care providers remains severely limited, often leading to delayed recognition, diagnosis, initiation appropriate treatment. This study aims address this knowledge gap conducting scoping review in the setting. Methods followed PRISMA-ScR guidelines Joanna Briggs Institute methodology, analyzing data from Cochrane CENTRAL, MEDLINE via PubMed, EMBASE, Web Science May 19, 2024. We included studies reported clinical features treatments patients with requiring care. Results Of 1262 reports identified, 78 met inclusion criteria, including 45 case reports/series, 17 observational studies, 15 reviews, one systematic review. Analysis 55 cases revealed median age 69 strong male predominance (54/55). ICU admission rates ranged 28 33%, mortality between 18 40%. Critical manifestations shock, hemophagocytic lymphohistiocytosis, acute respiratory distress syndrome, thrombosis, airway edema. Sepsis was cause death, other causes related organ failure, cardiovascular events, intestinal perforation. Treatment approaches combined conventional measures immunosuppressive immunomodulatory therapies, although infectious complications were frequently reported. Conclusion lack systematically analyzed focusing setting, suggesting significant understanding characteristics optimal for syndrome. Further research focused setting essential improve early develop standardized treatment protocols, ultimately outcomes complex population.

Language: Английский

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The Role of Morphology in Diagnosing MDS with Non-Clonal Cytopenias

Leukemia Research, Journal Year: 2025, Volume and Issue: unknown, P. 107703 - 107703

Published: April 1, 2025

Language: Английский

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