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急性髓系白血病未缓解患者移植前 WT1 mRNA 水平与异基因造血细胞移植后死亡率的比例关系。

The Proportional Relationship Between Pretransplant WT1 mRNA Levels and Risk of Mortality After Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Not in Remission.

机构信息

Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.

Department of Hematology, Tottori Prefectural Central Hospital, Tottori, Japan.

出版信息

Transplantation. 2019 Oct;103(10):2201-2210. doi: 10.1097/TP.0000000000002662.

Abstract

BACKGROUND

The relationship between the expression levels of Wilms' tumor-1 gene (WT1) mRNA in peripheral blood before allogeneic hematopoietic cell transplantation (allo-HCT) and risk of mortality in acute myeloid leukemia (AML) patients in noncomplete remission (non-CR) remains quite elusive.

METHODS

We retrospectively assessed the impact of the pretransplant WT1 mRNA level on survival after allo-HCT in non-CR AML patients.

RESULTS

A total of 125 AML patients, including 46 non-CR patients (36.8%), were analyzed. On multivariate analysis of non-CR AML patients, WT1 mRNA ≥5000 copies/μg RNA was significantly related to increased risk of mortality (hazard ratio, 2.7; 95% confidence interval, 1.3-5.5; P = 0.008). Furthermore, in the entire cohort, log10-transformed WT1 mRNA before allo-HCT was found to be significantly associated with the increased risk of mortality irrespective of whether the disease status was CR or non-CR, using Akaike's information criterion. As the pretransplant WT1 mRNA level elevated, the hazard ratio of mortality monotonically increased in a nonlinear manner regardless of remission status, suggesting that WT1 mRNA level in peripheral blood might reflect tumor burden.

CONCLUSIONS

This study demonstrated that the pretransplant WT1 mRNA level was a powerful prognostic factor in allo-HCT even for non-CR AML patients, and there may be a WT1 mRNA threshold in non-CR patients for benefiting from allo-HCT.

摘要

背景

异基因造血细胞移植(allo-HCT)前外周血 Wilms 瘤基因-1 基因(WT1)mRNA 表达水平与非完全缓解(non-CR)急性髓系白血病(AML)患者的死亡率之间的关系仍不太明确。

方法

我们回顾性评估了 allo-HCT 前 WT1 mRNA 水平对非 CR AML 患者移植后生存的影响。

结果

共分析了 125 例 AML 患者,包括 46 例非 CR 患者(36.8%)。对非 CR AML 患者进行多变量分析,WT1 mRNA≥5000 拷贝/μg RNA 与死亡率增加显著相关(危险比,2.7;95%置信区间,1.3-5.5;P=0.008)。此外,在整个队列中,使用赤池信息量准则发现,allo-HCT 前 log10 转化的 WT1 mRNA 与死亡率增加显著相关,无论疾病状态是 CR 还是非 CR。随着移植前 WT1 mRNA 水平的升高,死亡风险比呈非线性单调增加,无论缓解状态如何,这表明外周血中的 WT1 mRNA 水平可能反映肿瘤负荷。

结论

本研究表明,移植前 WT1 mRNA 水平是 allo-HCT 中即使对非 CR AML 患者也是一个强有力的预后因素,非 CR 患者可能存在一个从 allo-HCT 中获益的 WT1 mRNA 阈值。

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