Prevalence and outcome of VEXAS syndrome in unrelated hematopoietic cell transplantation for bone marrow failure

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.

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Publication Details

Journal
Clinical and Experimental Medicine
Published
2025-08-22
DOI
https://doi.org/10.1007/s10238-025-01832-7
Primary Topic
Otitis Media and Relapsing Polychondritis
Type
article
Field-Weighted Citation Impact
0.00

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article

Prevalence and outcome of VEXAS syndrome in unrelated hematopoietic cell transplantation for bone marrow failure

Tatsuya Imi, Seishi Ogawa, Kazuyoshi Hosomichi, Ken‐ichi Matsuoka et al.
Clinical and Experimental Medicine
Otitis Media and Relapsing Polychondritis
article

Prevalence and outcome of VEXAS syndrome in unrelated hematopoietic cell transplantation for bone marrow failure

Tatsuya Imi, Seishi Ogawa, Kazuyoshi Hosomichi, Ken‐ichi Matsuoka, Keisuke Kataoka, Natsumi Fushida, Hideyuki Nakazawa, Yoshitaka Zaimoku, Eriko Morishita, Tatsuo Ichinohe, Tetsuya Nishida, Fumihiko Ishimaru, Toshihiro Miyamoto, Yasuhito Nannya, Keishi Mizuguchi, Makoto Onizuka, Hiroki Mizumaki, Miku Kobayashi, Noriko Doki, Takashi Matsushita, Hiroki Mura, Hiroki Yoshino, Yasunori Ueda, Yoshiyuki Takahashi, Hiroko Ikeda, Tatsuya Hatada, Takahiro Fukuda, Takashi Koike, Yoshio Kano, Yoshiko Atsuta, Yuta Katayama
article en

Abstract

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.

Clinical and Experimental MedicineVol. 25(1)
Kanazawa University (JP), Hiroshima University (JP), Tokai University (JP), Shinshu University (JP), Tokyo University of Pharmacy and Life Sciences (JP), Aichi Medical University (JP), Keio University (JP), Kyoto University (JP), Japanese Red Cross Society, Japan (JP), Tokyo Metropolitan Komagome Hospital (JP), Kurashiki Central Hospital (JP), Okayama University Hospital (JP), Kanazawa University Hospital (JP), Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital (JP), Japanese Red Cross Nagoya Daiichi Hospital (JP), The Japanese Data Center for Hematopoietic Cell Transplantation (JP), Nagoya University (JP), The University of Tokyo (JP), Kindai University (JP)
Nippon Shinyaku, Kanazawa University, Ministry of Education, Culture, Sports, Science and Technology
Openalex Percentile: Top 67%
Otitis Media and Relapsing Polychondritis
DOIOpen Access PDFOpenAlex
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