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新诊断的急性髓系白血病患者在接受异基因造血干细胞移植缓解诱导后早期WT1 mRNA降低的临床结果

Clinical Outcomes of Early WT1 mRNA Reduction After Remission Induction in Newly Diagnosed Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

作者信息

Tsushima Takafumi, Kimeda Chiharu, Yoda Natsumi, Matsuo Kosuke, Tanaka Kazusuke, Hatanaka Yasuhito, Matsumoto Rena, Shimoji Sonoko, Utsu Yoshikazu, Masuda Shin-Ichi, Aotsuka Nobuyuki

机构信息

Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, Narita, Japan.

Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, Narita, Japan.

出版信息

Transplant Cell Ther. 2025 Mar;31(3):168.e1-168.e12. doi: 10.1016/j.jtct.2024.12.007. Epub 2024 Dec 16.

DOI:10.1016/j.jtct.2024.12.007
PMID:39694194
Abstract

Wilms' Tumor 1 (WT1) mRNA is a non-specific marker of measurable residual disease in acute myeloid leukemia (AML). Few studies have focused on the prognostic value of WT1 mRNA after initial remission induction of patients with AML who have received transplant treatments. Thus, we retrospectively analyzed the clinical features and prognostic impact of WT1 mRNA reduction in patients with AML after initial remission induction at our hospital. We classified the reduction in WT1 mRNA levels using logarithmic stratification, with particular focus on the prognostic impact of a 3-log reduction after initial remission induction. This single-center, retrospective, observational study included 71 consecutive patients with AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between April 2013 and June 2023 and had WT1 mRNA quantified. Patients were grouped based on whether a 3-log reduction was observed during follow-up (N=30) or not (N=41). Among patients who did not achieve a 3-log reduction, European Leukemia Net (ELN) 2022 adverse risk was more common, and fewer patients showed complete hematological responses at transplantation. Patients who reached a 3-log reduction in WT1 mRNA after the initial remission induction had significantly longer overall survival (OS) and progression-free survival (PFS) and a lower relapse rate than patients who had not reached a 3-log reduction (2-year OS: 79.7% vs. 27.5%, 2-year PFS: 83.1% vs. 11.7% and 2-year cumulative relapse rate: 5.9% vs. 81.2%). In multivariate analysis, a 3-log reduction in WT1 mRNA after initial remission induction and ELN 2022 adverse risk by genetics were significantly associated with OS and PFS. We identified that patients with AML undergoing HSCT with an early and deep 3-log reduction in WT1 mRNA after initial remission induction were associated with low relapse rates and better long-term prognosis. Our data highlight the importance of WT1 mRNA reduction after initial remission induction.

摘要

肾母细胞瘤1(WT1)mRNA是急性髓系白血病(AML)中可测量残留病的非特异性标志物。很少有研究关注接受移植治疗的AML患者初始缓解诱导后WT1 mRNA的预后价值。因此,我们回顾性分析了我院AML患者初始缓解诱导后WT1 mRNA降低的临床特征及其对预后的影响。我们使用对数分层对WT1 mRNA水平的降低进行分类,特别关注初始缓解诱导后3-log降低的预后影响。这项单中心、回顾性、观察性研究纳入了2013年4月至2023年6月期间连续71例接受异基因造血干细胞移植(allo-HSCT)且WT1 mRNA定量的AML患者。根据随访期间是否观察到3-log降低将患者分组(n = 30)或未观察到(n = 41)。在未实现3-log降低的患者中,欧洲白血病网络(ELN)2022不良风险更为常见,移植时显示完全血液学缓解的患者较少。初始缓解诱导后WT1 mRNA达到3-log降低的患者总生存期(OS)和无进展生存期(PFS)显著更长,复发率低于未达到3-log降低的患者(2年OS:79.7%对27.5%,2年PFS:83.1%对11.7%,2年累积复发率:5.9%对81.2%)。多因素分析中,初始缓解诱导后WT1 mRNA 3-log降低和ELN 2022遗传学不良风险与OS和PFS显著相关。我们发现,初始缓解诱导后WT1 mRNA早期且深度降低3-log的接受HSCT的AML患者复发率低,长期预后较好。我们的数据突出了初始缓解诱导后WT1 mRNA降低的重要性。

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