Department of Clinical Immunology and Allergy, Flinders Medical Centre, Bedford Park, South Australia, Australia.
School of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.
Clin Rheumatol. 2024 Nov;43(11):3565-3575. doi: 10.1007/s10067-024-07160-7. Epub 2024 Sep 30.
Vacuolation, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a multisystem disease due to a genetic mutation in the ubiquitin-activating enzyme (UBA1). Allogeneic haematopoietic stem cell transplantation (allo-HSCT) offers both therapeutic and cure but also carries significant risks. A review of VEXAS and HSCT cases was undertaken. Thirty-three patients were identified; majority males (n = 32, 97.0%), median time from symptoms to HSCT: 3 years (IQR 2.0-4.8) and median age of 59 years (IQR 52.5-65.5). UBA1 mutation Met41Thr was most common (11/32, 34.4%). The median variant allele frequency was 56.5% (IQR 43.0-73.5) with no correlation with increasing age. Prior to HSCT, 4.5 (IQR 2.8-6) treatments were trialled. Peripheral blood HSCT (30/31, 96.8%) and HLA-matched, unrelated donor (18/32, 56.3%) were most common. Conditioning regimens varied, with reduced intensity treatment with fludarabine as a co-agent most frequently administered (12/31, 38.7%). Both acute and/or chronic GVHD (18/32, 56.3%) and infections were common (12/32, 37.5%). Overall, 27 individuals (81.8%) were alive, and those undergoing HSCT prospectively had median follow up of 9 months (IQR 3.8-14.4). Of the six deceased, infection was implicated in four. In 11 cases with post-HSCT molecular data, a complete eradication of UBA1 mutation was reported. In summary, while consensus treatment strategy regarding VEXAS is lacking, this review highlights HSCT may remain not only a therapeutic option but also enable cure. However, considerations regarding comorbidities, concurrent haematological disorders as well as overall risks of GVHD and infections need to be made. Key points • Very few reported prospective cases of VEXAS and allogeneic haematopoietic stem cell transplantation (allo-HSCT) have been reported. • While risks of graft versus host disease and infection remain barriers, this treatment modality remains an option for selected patients. • Allo-HSCT is the only treatment strategy which can remove the UBA1 mutation.
空泡化、E1 酶、X 连锁、自炎症、体细胞 (VEXAS) 综合征是一种多系统疾病，由泛素激活酶 (UBA1) 的基因突变引起。异基因造血干细胞移植 (allo-HSCT) 既具有治疗作用，也能根治，但也存在重大风险。我们对 VEXAS 和 HSCT 病例进行了回顾。共确定了 33 例患者；大多数为男性 (n = 32，97.0%)，从症状到 HSCT 的中位时间为 3 年 (IQR 2.0-4.8)，中位年龄为 59 岁 (IQR 52.5-65.5)。UBA1 突变 Met41Thr 最为常见 (11/32，34.4%)。中位变异等位基因频率为 56.5% (IQR 43.0-73.5)，与年龄增加无关。在 HSCT 之前，有 4.5 (IQR 2.8-6) 种治疗方法进行了试验。外周血 HSCT (30/31，96.8%)和 HLA 匹配的无关供体 (18/32，56.3%)最为常见。预处理方案各不相同，最常使用含有氟达拉滨的减强度治疗作为协同剂 (12/31，38.7%)。急性和/或慢性移植物抗宿主病 (18/32，56.3%)和感染均很常见 (12/32，37.5%)。总体而言，有 27 人 (81.8%)存活，前瞻性接受 HSCT 的患者中位随访时间为 9 个月 (IQR 3.8-14.4)。在 6 例死亡患者中，有 4 例与感染有关。在 11 例有 HSCT 后分子数据的病例中，报告了 UBA1 突变的完全消除。总之，尽管 VEXAS 的共识治疗策略尚未确定，但本综述强调 HSCT 不仅仍然是一种治疗选择，而且还可以实现根治。然而，需要考虑合并症、同时存在的血液系统疾病以及移植物抗宿主病和感染的总体风险。关键点• 非常少的 VEXAS 和异基因造血干细胞移植 (allo-HSCT) 的前瞻性病例报告。• 虽然移植物抗宿主病和感染的风险仍然是障碍，但这种治疗方式仍然是某些患者的选择。• allo-HSCT 是唯一可以消除 UBA1 突变的治疗策略。
