Yuan Xiaolin, Ni Lihong, Chen Ting, Wu Yibo, Lai Xiaoyu, Liu Lizhen, Xu Zhengli, Xu Yajing, Yang Tingting, Lu Ying, Cao Weijie, Chen Yi, Miao Kourong, Ouyang Guifang, Yang Luxin, Zhang Xi, Wang Yu, Luo Yi
Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China; Department of Hematology, Zhejiang Cancer Hospital & Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China.
Department of Hematology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.
Transplant Cell Ther. 2025 Aug 5. doi: 10.1016/j.jtct.2025.07.012.
Acute myeloid leukemia with NUP98 rearrangements (NUP98r) is associated with poor prognosis, and while allo-HSCT remains the primary curative approach, its efficacy in NUP98r patients is still uncertain. The prognostic impact of NUP98 fusion partners, accompanying genetic alterations, and NUP98r dynamics is unclear.
We retrospectively analyzed 56 adult patients with NUP98r AML undergoing allo-HSCT across multiple centers. Primary outcomes included overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR).
The most common NUP98r were NUP98::HOXA9 and NUP98::NSD1. With a median follow-up of 755 days, the 2-year CIR, DFS, and OS rates were 28.4%, 69.8%, and 73.0%. Pre-transplant NUP98r status demonstrated no significant association with outcomes in complete remission patients, while nonremission status correlated with higher CIR and reduced survival. NUP98r positivity at 1 month post-HSCT predicted higher 2-year CIR (60.0% versus 21.5%, P = .013), reduced DFS (40.0% versus 78.5%, P = .008) and OS (40.0% versus 84.5%, P = .003). Outcomes worsened at 3 and 6 months, with 100% CIR in the NUP98r positive at 6 months. Multivariable analysis confirmed 1-month post-HSCT NUP98r positivity as an independent predictor of relapse and mortality, whereas pre-transplant NUP98r status lacked prognostic significance.
Patients with detectable NUP98r post-HSCT showed higher relapse risk and mortality, indicating the necessity for early molecular surveillance and early intervention trials in this high-risk subgroup.
伴有核孔蛋白98重排（NUP98r）的急性髓系白血病预后较差，虽然异基因造血干细胞移植（allo-HSCT）仍是主要的治愈方法，但其在NUP98r患者中的疗效仍不确定。NUP98融合伴侣、伴随的基因改变以及NUP98r动态变化的预后影响尚不清楚。
我们对多个中心接受allo-HSCT的56例成年NUP98r急性髓系白血病患者进行了回顾性分析。主要结局包括总生存期（OS）、无病生存期（DFS）和累积复发率（CIR）。
最常见的NUP98r是NUP98::HOXA9和NUP98::NSD1。中位随访755天，2年CIR、DFS和OS率分别为28.4%、69.8%和73.0%。移植前NUP98r状态在完全缓解患者中与结局无显著相关性，而非缓解状态与较高的CIR和较低的生存率相关。HSCT后1个月时NUP98r阳性预测2年CIR更高（60.0%对21.5%，P = 0.013）、DFS降低（40.0%对78.5%，P = 0.008）和OS降低（40.0%对84.5%，P = 0.003）。3个月和6个月时结局恶化，6个月时NUP98r阳性患者的CIR为100%。多变量分析证实HSCT后1个月时NUP98r阳性是复发和死亡的独立预测因素，而移植前NUP98r状态缺乏预后意义。
HSCT后可检测到NUP98r的患者显示出较高的复发风险和死亡率，表明有必要对这一高危亚组进行早期分子监测和早期干预试验。
