Therapeutic Outcomes in VEXAS Syndrome: A Multicenter Comparative Cohort of Allogeneic Hematopoietic Stem Cell Transplantation and Hypomethylating Agents

First author: Saubia Fathima

Journal: American Journal of Hematology, 2026

Link to the article: https://pubmed.ncbi.nlm.nih.gov/42260942/

Authors of the abstract: Pr Sophie Georgin-Lavialle et Pr Olivier Kosmider

Key points

- In this multicenter cohort of 66 patients with VEXAS syndrome, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was associated with better overall survival than hypomethylating agents (HMAs).

- Allo-HSCT achieved molecular remission in all evaluable patients, compared with 22% under HMAs.

- Corticosteroid withdrawal was markedly more frequent after transplantation than with HMAs.

- HMAs -mainly azacitidine- remained active in some patients, but with a high rate of discontinuation due to toxicity or lack of efficacy.

- These findings support allo-HSCT as a potentially curative strategy in selected patients.

Summary

VEXAS syndrome is an acquired hematoinflammatory disease caused by somatic mutations in the UBA1 gene, affecting mainly men over 50 years of age. It combines systemic autoinflammatory manifestations, cytopenias, and sometimes an associated myelodysplastic syndrome. Management remains challenging, with frequent corticosteroid dependence and often limited effectiveness of steroid-sparing treatments. In this context, this retrospective multicenter U.S. study compared outcomes of two approaches targeting the pathological clone: hypomethylating agents and allogeneic hematopoietic stem cell transplantation.

Sixty-six patients with confirmed VEXAS were included between 2019 and 2025, including 31 treated with allo-HSCT and 35 with an HMA, mainly azacitidine. Indications for therapy were glucocorticoid-refractory inflammation, progressive bone marrow failure or associated myeloid neoplasia, or combinations of these manifestations. The two groups were broadly comparable clinically and biologically, except for older age in the HMA group.

After a median follow-up of 18 months, 14 deaths were observed 3 in the transplant group and 11 in the HMA group. Allo-HSCT was associated with a significant improvement in overall survival, with median survival not reached versus 29.6 months with HMAs, including after adjustment for age and comorbidities. This superiority persisted across several sensitivity analyses, strengthening the robustness of the signal despite methodological limitations inherent to the retrospective design.

Beyond survival, allo-HSCT was associated with major clinical and biological benefit. All evaluable patients achieved molecular remission, with no re-emergence of the UBA1 clone at last follow-up. Corticosteroid discontinuation was also far more frequent after transplantation, with steroid cessation in 58% of patients, versus only 6% with HMAs. By contrast, HMAs showed real but more modest activity, with molecular remission in 22% of evaluable patients and a high treatment discontinuation rate. Nearly one in two patients stopped treatment, mainly due to infections, prolonged cytopenias, toxicity, or lack of response.

Overall, this North American study suggests that allo-HSCT is currently, as expected, the most effective and potentially curative option for eligible patients with VEXAS, particularly in severe disease, steroid dependence, or bone marrow involvement. HMAs may still have a role in patients not immediately eligible for transplant, as bridging therapy or a step toward transplantation, but in this study their benefit appeared more modest and less durable.

Premenstrual syndrome and inflammatory activity in adolescent Familial Mediterranean Fever

• English title: Premenstrual syndrome and inflammatory activity in adolescent familial Mediterranean fever

• First author: Nigar Aliyeva

• Journal: Rheumatology

• Reference: Rheumatology (Oxford). 2026:keag169. doi: 10.1093/rheumatology/keag169. Online ahead of print.

• PubMed link: https://pubmed.ncbi.nlm.nih.gov/41936095/

• Abstracted by: Dr. Catherine Grandpeix-Guyodo

Key points - Premenstrual syndrome and inflammatory activity in adolescent familial Mediterranean fever

1. Premenstrual syndrome (PMS) is less frequent in FMF patients treated with colchicine than in healthy controls.

2. In FMF patients, PMS is associated with higher disease activity, systemic inflammation, and poorer treatment adherence. PMS severity appears to be proportional to the level of inflammation.

3. Colchicine may prevent PMS by reducing inflammation, which could explain the lower prevalence of PMS in colchicine-treated FMF patients compared with controls.

Introduction

PMS is linked to hormonal fluctuations, but immunological and inflammatory mechanisms also seem to contribute to symptom expression. Cytokine fluctuations during the menstrual cycle and the direct activation of the pyrin inflammasome by steroid catabolites support a direct link between reproductive physiology and inflammatory pathways.

However, there are limited clinical data on PMS in adolescents with FMF, and on its association with disease activity or adherence to colchicine treatment.

Patients and methods

This was a prospective, single-center Turkish study comparing adolescents aged 12 to 18 years with and without FMF, focusing on PMS. Menarche had to have occurred at least 6 months earlier; cycles had to be regular and bleeding last fewer than 7 days. FMF patients were required to have two pathogenic MEFV variants. Disease activity score (AIDAI), number of attacks per month (1 versus several), and biological inflammatory markers were collected, along with an assessment of PMS severity (PMSS).

Results

Mean age in both groups was 16 years. Mean height was significantly lower in the FMF group, while weight did not differ. Half of the FMF patients had not experienced a flare in the previous 6 months. Among 40 adolescents with FMF treated with colchicine, only 45% had PMS, compared with 75% among 40 controls. The difference in dysmenorrhea prevalence was not statistically significant, but longer menstruation and heavier bleeding were reported in FMF patients (p<0.05). PMS was more frequent and more severe in controls than in FMF patients.

Among FMF patients, those with PMS had higher AIDAI scores and more frequent FMF attacks. Blood inflammatory markers were also higher in this group. A clear correlation was observed between attack frequency and PMS severity.

There was also an association between PMS frequency and poor adherence to colchicine treatment.

Discussion

PMS appears less frequent in FMF, but PMS symptoms increase with inflammation. This suggests that colchicine, by modulating inflammation, could reduce hormonal symptoms and thus decrease PMS frequency. PMS is also more common in FMF patients with poor adherence to colchicine.

During the menstrual phase, decreased estrogen and increased IL-6 have been shown to intensify inflammation, which aligns with the observation that menstruation can trigger FMF attacks. Colchicine could therefore attenuate inflammatory fluctuations and modulate PMS.

Regarding the higher frequency of heavy bleeding during menstruation in FMF patients, one hypothesis is repeated use of anti-inflammatory drugs.

This study has limitations, including the small cohort size and its single-center design.

Conclusion

PMS is less frequent in FMF patients treated with colchicine than in healthy controls. In FMF patients, PMS is associated with higher disease activity, systemic inflammation, and poorer treatment adherence. Colchicine may prevent PMS by reducing inflammation, which could explain the lower frequency of PMS compared with the control population.

VEXAS syndrome: key points to remember

In this article, Journal des Femmes Santé reviews the causes, symptoms, and management of the disease, with insights from Professor Sophie Georgin-Lavialle, an internist at Tenon Hospital.

VEXAS syndrome is a rare inflammatory disease, first described in 2020. Its name is an acronym standing for Vacuoles, E1 enzyme (UBA1), X-linked, Autoinflammatory, Somatic. It is caused by an acquired (somatic) mutation of the UBA1 gene, located on the X chromosome, leading to excessive chronic inflammation throughout the body.

This disease primarily affects men over the age of 50. Because the mutations are not present at birth, symptoms appear in adulthood (the youngest patient described was 46 years old).

Common symptoms include:

• Anemia

• Persistent fever

• Severe fatigue

• Pain in large joints

• Skin lesions

• Weight loss and loss of appetite

• Cartilage inflammation (ears, nose – chondritis)

• Possible lung involvement

• Markedly elevated inflammatory markers (CRP)

Diagnosis relies on genetic sequencing, which has made it possible to identify many patients who were previously misdiagnosed with other inflammatory or hematological diseases.

There is no typical acute phase: inflammation is continuous, sometimes with flares.

VEXAS syndrome remains poorly understood, particularly regarding why some individuals develop this mutation while others do not.

https://sante.journaldesfemmes.fr/fiches-maladies/2905657-syndrome-vexas-symptomes-traitement-c-est-quoi/