Zaimoku Yoshitaka, Imi Tatsuya, Hatada Tatsuya, Mizumaki Hiroki, Mura Hiroki, Yoshino Hiroki, Kano Yui, Kobayashi Miku, Morishita Eriko, Fushida Natsumi, Matsushita Takashi, Mizuguchi Keishi, Ikeda Hiroko, Nannya Yasuhito, Ogawa Seishi, Hosomichi Kazuyoshi, Doki Noriko, Katayama Yuta, Koike Takashi, Matsuoka Ken-Ichi, Nishida Tetsuya, Takahashi Yoshiyuki, Kataoka Keisuke, Nakazawa Hideyuki, Ueda Yasunori, Fukuda Takahiro, Ichinohe Tatsuo, Ishimaru Fumihiko, Onizuka Makoto, Atsuta Yoshiko, Miyamoto Toshihiro
Department of Hematology, Kanazawa University Hospital, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.
Innovative Clinical Research Center, Kanazawa University, Kanazawa, Japan.
Clin Exp Med. 2025 Aug 22;25(1):300. doi: 10.1007/s10238-025-01832-7.
VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic) is a recently identified clonal disorder caused by somatic UBA1 mutations in hematopoietic stem cells, leading to bone marrow failure (BMF) and systemic inflammation. We screened 1771 patients with BMF who underwent unrelated hematopoietic cell transplantation in Japan between 1995 and 2020 using multitarget real-time PCR. The diagnoses included myelodysplastic syndrome (MDS, n = 1139), myeloproliferative neoplasms (n = 125), plasma cell neoplasms (n = 23), acquired BMF (n = 395), and congenital BMF (n = 89). Pathogenic UBA1 mutations were detected in two male patients with MDS (aged 48 and 63 years), corresponding to a prevalence of 0.11% in the overall cohort and 0.18% in MDS cases; an additional 70-year-old male was diagnosed outside of the cohort. All three underwent unrelated bone marrow transplantation following fludarabine and busulfan-based conditioning. The first and third patients died of idiopathic pneumonia syndrome 5 and 28 months after transplantation. In the third patient, UBA1-mutant cells persisted at low frequency in skin graft-versus-host disease tissue despite clearance from his blood. The second patient survived without relapse or graft-versus-host disease at 28 months. Although VEXAS syndrome is rare among unrelated HCT recipients with malignant and non-malignant BMF in the historical cohort, HCT is positioned as a potentially curative, yet high-risk strategy. Additional studies are essential to refine patient selection, optimize transplant timing, and improve management strategies to mitigate risk and enhance survival. Therefore, the role of tissue-residual UBA1-mutant clones in post-transplant complications warrants further investigation.
VEXAS综合征（空泡、E1酶、X连锁、自身炎症性和体细胞性）是一种最近发现的克隆性疾病，由造血干细胞中的体细胞UBA1突变引起，导致骨髓衰竭（BMF）和全身炎症。我们使用多靶点实时PCR对1995年至2020年期间在日本接受非亲缘造血细胞移植的1771例BMF患者进行了筛查。诊断包括骨髓增生异常综合征（MDS，n = 1139）、骨髓增殖性肿瘤（n = 125）、浆细胞肿瘤（n = 23）、获得性BMF（n = 395）和先天性BMF（n = 89）。在两名患有MDS的男性患者（年龄分别为48岁和63岁）中检测到致病性UBA1突变，在整个队列中的患病率为0.11%，在MDS病例中的患病率为0.18%；另有一名70岁男性在队列之外被诊断出。所有三名患者在接受基于氟达拉滨和白消安的预处理后均接受了非亲缘骨髓移植。第一名和第三名患者分别在移植后5个月和28个月死于特发性肺炎综合征。在第三名患者中，尽管其血液中UBA1突变细胞已清除，但在皮肤移植物抗宿主病组织中仍以低频率持续存在。第二名患者在28个月时存活，无复发或移植物抗宿主病。尽管在历史队列中，VEXAS综合征在患有恶性和非恶性BMF的非亲缘造血细胞移植受者中很少见，但造血细胞移植被认为是一种潜在的治愈性但高风险的策略。进一步的研究对于优化患者选择、确定最佳移植时机以及改进管理策略以降低风险和提高生存率至关重要。因此，组织残留的UBA1突变克隆在移植后并发症中的作用值得进一步研究。
