Department of Hematology, Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Hematology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Biol Blood Marrow Transplant. 2019 Oct;25(10):1925-1932. doi: 10.1016/j.bbmt.2019.05.033. Epub 2019 Jun 4.
The absence of relevant guidelines for Wilms tumor 1 (WT1) gene quantification as a measurable residual disease (MRD) assessment for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) has limited the widespread use in practice. We investigated optimal time points, thresholds, and candidates for the bone marrow WT1 MRD assay in 425 consecutive patients with AML who underwent allo-HSCT. WT1 expression kinetics before allo-HSCT and at 1 or 3 months after allo-HSCT were determined by real-time PCR using the European LeukemiaNet (ELN) normalized method. Relapsed patients had significantly higher WT1 levels before allo-HSCT and at 3 months after allo-HSCT. The best time point for the WT1 MRD assay was before allo-HSCT by the receiver operating characteristic curve. Among various thresholds, 250 copies recommended from ELN researchers were mostly predictive of post-transplant relapse. In multivariate analysis, WT1 MRD positivity independently predicted relapse, resulting in inferior survival. In subgroup analyses, pretransplant WT1 MRD positivity was predictive of post-transplant relapse in the intermediate group, whereas WT1 MRD positivity occurred at 3 months after allo-HSCT in favorable and adverse risk groups. Among MRD-positive patients before allo-HSCT, all patients who were MRD positive at 3 months relapsed within 6 months. The WT1 MRD assay before allo-HSCT or 3 months after allo-HSCT is useful for predicting post-transplant relapse with a different significance in each risk group by time points, showing the benefit of multiple tests over time. Such monitoring is particularly available in patients with AML without specific molecular targets.
由于缺乏针对接受异基因造血干细胞移植（allo-HSCT）的急性髓系白血病（AML）患者的 Wilms 肿瘤 1 （WT1）基因定量作为可测量残留疾病（MRD）评估的相关指南，因此该方法在实践中的广泛应用受到限制。我们研究了 425 例连续接受 allo-HSCT 的 AML 患者的骨髓 WT1-MRD 检测的最佳时间点、阈值和候选物。通过使用欧洲白血病网（ELN）标准化方法的实时 PCR 确定 allo-HSCT 前和 allo-HSCT 后 1 或 3 个月的 WT1 表达动力学。复发患者在 allo-HSCT 前和 allo-HSCT 后 3 个月的 WT1 水平明显更高。通过受试者工作特征曲线，WT1-MRD 检测的最佳时间点是 allo-HSCT 前。在各种阈值中，ELN 研究人员推荐的 250 拷贝最能预测移植后复发。在多变量分析中，WT1-MRD 阳性独立预测复发，导致生存不良。在亚组分析中，移植前 WT1-MRD 阳性预测中间组移植后复发，而在有利和不利风险组中，WT1-MRD 阳性发生在 allo-HSCT 后 3 个月。在 allo-HSCT 前 WT1-MRD 阳性的患者中，所有在 3 个月时 WT1-MRD 阳性的患者在 6 个月内均复发。allo-HSCT 前或 allo-HSCT 后 3 个月的 WT1-MRD 检测可通过时间点预测移植后复发，在每个风险组中具有不同的意义，表明随着时间的推移多次检测的益处。这种监测在没有特定分子靶点的 AML 患者中尤其可用。
