Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Department of Hematology, Tottori Prefectural Central Hospital, Tottori, Japan.
Transplantation. 2019 Oct;103(10):2201-2210. doi: 10.1097/TP.0000000000002662.
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.
We retrospectively assessed the impact of the pretransplant WT1 mRNA level on survival after allo-HCT in non-CR AML patients.
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.
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.
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。
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。
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。
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。