异基因造血干细胞移植前后外周血 WT1 基因表达是 AML 的临床相关预后标志物：一项单中心 14 年经验。
WT1 Gene Expression in Peripheral Blood Before and After Allogeneic Stem Cell Transplantation is a Clinically Relevant Prognostic Marker in AML - A Single-center 14-year Experience.
机构信息
Department of Bone Marrow Transplant, Institute of Hematology and Blood Transfusion, Prague, Czech Republic; Institute of Clinical and Experimental Hematology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Department of Bone Marrow Transplant, Institute of Hematology and Blood Transfusion, Prague, Czech Republic; Institute of Clinical and Experimental Hematology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
出版信息
Clin Lymphoma Myeloma Leuk. 2021 Feb;21(2):e145-e151. doi: 10.1016/j.clml.2020.09.008. Epub 2020 Oct 12.
BACKGROUND
This work summarizes our experience with WT1 monitoring before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
PATIENTS AND METHODS
The expression of WT1 gene was measured by real-time polymerase chain reaction in peripheral blood according to the European Leukemia Net recommendations. Between May 2005 and August 2019, we analyzed 147 consecutive patients with acute myeloid leukemia with high WT1 expression at diagnosis, transplanted in first (CR1) or second (CR2) complete remission.
RESULTS
At the time of allo-HSCT, 107 patients had WT1-normal expression (WT1 ≤ 50 copies), and 40 patients had WT1-high expression. The median follow-up was 21 months. The estimated 5-year overall survival and event-free survival was significantly better in the WT1-normal cohort (65% and 57% vs. 37% and 25%; P = .0003 and P < .0001, respectively) and 5-year cumulative incidence of relapse was significantly lower in the WT1-normal group (19% vs. 53%; P < .0001). Five-year non-relapse mortality was not significantly different (20% and 23%). Multivariate analysis revealed WT1-high expression and acute graft-versus-host disease grade 3/4 as significantly negative prognostic factors for OS. Overall, 49 patients developed WT1 molecular relapse in the post-transplant period; in 14 cases, the therapeutic intervention was done. In all but 1 relapsed patient where WT1 minimal residual disease (MRD) was monitored (38 patients), we detected WT1-high levels (sensitivity of 97%).
CONCLUSION
The results of the analysis confirmed our previous experience that WT1 status before allo-HSCT is a strong prognostic factor for both OS and relapse risk. In addition, we confirmed the usefulness of this marker for MRD monitoring after allo-HSCT. The main advantage is the possibility of frequent MRD monitoring in peripheral blood and early bone marrow examination based on WT1-high expression.
背景
本研究总结了我们在异基因造血干细胞移植（allo-HSCT）前后监测 WT1 的经验。
患者与方法
根据欧洲白血病网的建议，通过实时聚合酶链反应（PCR）在外周血中测量 WT1 基因的表达。在 2005 年 5 月至 2019 年 8 月期间，我们分析了 147 例初诊时具有高 WT1 表达的急性髓系白血病患者，这些患者均接受了在首次（CR1）或第二次（CR2）完全缓解后的 allo-HSCT。
结果
在 allo-HSCT 时，107 例患者的 WT1 表达正常（WT1≤50 拷贝），40 例患者的 WT1 表达升高。中位随访时间为 21 个月。WT1 表达正常组的 5 年总生存率和无事件生存率明显更好（65%和 57% vs. 37%和 25%；P=0.0003 和 P<0.0001），WT1 表达正常组的 5 年累积复发率明显更低（19% vs. 53%；P<0.0001）。5 年非复发死亡率无显著差异（20%和 23%）。多变量分析显示，WT1 高表达和急性移植物抗宿主病 3/4 级是 OS 的显著负预后因素。总体而言，在移植后期间有 49 例患者发生 WT1 分子复发，其中 14 例进行了治疗干预。在所有但 1 例监测 WT1 微小残留病（MRD）的复发患者（38 例）中，我们均检测到 WT1 高水平（敏感性为 97%）。
结论
分析结果证实了我们之前的经验，即在 allo-HSCT 之前，WT1 状态是 OS 和复发风险的一个强有力的预后因素。此外，我们还证实了该标志物在 allo-HSCT 后用于 MRD 监测的有效性。主要优点是能够在外周血中频繁监测 MRD，并基于 WT1 高表达进行早期骨髓检查。
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