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Minimal Residual Disease at First Achievement of Complete Remission Predicts Outcome in Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

机译:首次完全缓解后实现的最小残留疾病可预测费城染色体阴性急性淋巴细胞白血病成人患者的结果。

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摘要

We evaluated the prognostic effect of minimal residual disease at first achievement of complete remission (MRD at CR1) in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL). A total of 97 patients received treatment in our center between 2007 and 2012 were retrospectively reviewed in this study. Patients were divided into two arms according to the post-remission therapy (chemotherapy alone or allogeneic hematopoietic stem cell transplantation (allo-HSCT)) they received. MRD was detected by four-color flow cytometry. We chose 0.02% and 0.2% as the cut-off points of MRD at CR1 for risk stratification using receiver operating characteristic analysis. The 3-year overall survival (OS) and leukemia free survival (LFS) rates for the whole cohort were 46.2% and 40.5%. MRD at CR1 had a significantly negative correlation with survival in both arms. Three-year OS rates in the chemotherapy arm were 70.0%, 25.2%, 0% (P = 0.003) for low, intermediate, and high levels of MRD at CR1, respectively. Three-year OS rates in the transplant arm were 81.8%, 64.3%, 27.3% (P = 0.005) for low, intermediate, and high levels of MRD at CR1, respectively. Multivariate analysis confirmed that higher level of MRD at CR1 was a significant adverse factor for OS and LFS. Compared with chemotherapy alone, allo-HSCT significantly improved LFS rates in patients with intermediate (P = 0.005) and high (P = 0.022) levels of MRD at CR1, but not patients with low level of MRD at CR1 (P = 0.851). These results suggested that MRD at CR1 could strongly predict the outcome of adult ALL. Patients with intermediate and high levels of MRD at CR1 would benefit from allo-HSCT.
机译:我们评估了费城染色体阴性急性淋巴细胞白血病(ALL)的成年患者在首次完全缓解(CR1时达到MRD)时最小残留病的预后效果。本研究回顾性分析了2007年至2012年间在我们中心接受治疗的97位患者。根据他们接受的缓解后治疗(单独的化学治疗或同种异体造血干细胞移植(allo-HSCT))将患者分为两部分。通过四色流式细胞仪检测MRD。我们使用接收器工作特征分析,选择0.02%和0.2%作为CR1的MRD临界点,以进行风险分层。整个队列的3年总生存率和无白血病生存率分别为46.2%和40.5%。 CR1处的MRD与两组生存率均呈显着负相关。对于CR1,MRD的低,中和高水平,化疗组的三年OS率分别为70.0%,25.2%,0%(P = 0.003)。对于CR1,MRD的低,中和高水平,移植组的三年OS发生率分别为81.8%,64.3%,27.3%(P = 0.005)。多变量分析证实,CR1处较高的MRD水平是OS和LFS的重要不利因素。与单独化疗相比,同种异体造血干细胞移植显着提高了CR1时MRD中级(P = 0.005)和高(P = 0.022)患者的LFS率,而CR1中MRD较低的患者(P = 0.851)不能显着提高LFS率。这些结果表明CR1的MRD可以强烈预测成人ALL的预后。在CR1处于MRD中高水平的患者将受益于allo-HSCT。

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