Li Z R, Zhao T, Liu Y R, Wang Y Z, Xu L P, Zhang X H, Wang Y, Jiang H, Chen Y Y, Chen H, Han W, Yan C H, Wang J, Jia J S, Huang X J, Jiang Q
Peking University People's Hospital, Peking University Institute of Hematology, Beijing 100044, China.
Zhonghua Xue Ye Xue Za Zhi. 2019 Jul 14;40(7):554-560. doi: 10.3760/cma.j.issn.0253-2727.2019.07.004.
To explore the significance of minimal residual disease (MRD) in predicting prognosis and guiding therapy of adults with Philadelphia-chromosome negative acute lymphoblastic leukemia (Ph(-) ALL) in high-risk. Data of newly diagnosed adults with Ph(-) ALL in high-risk who achieved CR were reviewed. Variables associated with outcome were identified by COX regression model and Landmark analysis. A total of 177 patients, 99 (56%) cases male with a median age of 40 years (range, 16-65 years) were included in this study. Of them, 95 (54%) patients received allo-HSCT in CR(1). Multivariate analyses showed that MRD negativity after the first cycle of consolidation (=0.52, 95% 0.30-0.89, =0.017) and achieving CR within 4 weeks (=0.43, 95% 0.24-0.79, =0.006) were the factors significantly-associated with longer DFS, and allo-HSCT was associated with both longer DFS (=0.13, 95% 0.08-0.22, <0.001) and OS (=0.24, 95% 0.15-0.41, <0.001) . Landmark analysis was performed on 121 patients, of 85 patients achieving MRD negativity after the first cycle of consolidation, multivariate analyses showed that MRD negativity after the third cycle of consolidation was significantly-associated with longer DFS (=0.18, 95% 0.05-0.64, =0.008) and OS (=0.14, 95% 0.04-0.50, =0.003) . For the patients achieving MRD negativity after both the first and the third cycles of consolidation, the 3-year DFS rate in the allo-HSCT cohort had a higher trend compared with that in the chemotherapy cohort (75.2% 51.3%, =0.082) , however, the 3-year OS rates in the 2 cohorts were similar (72.7% 68.7%, =0.992) . In those with MRD positivity after the first and/or the third cycle of consolidation, 3-year DFS (64.8% 33.3%, =0.006) and OS (77.0% 33.3%, =0.028) rates in the allo-HSCT cohort were significantly higher than those in the chemotherapy cohort, and similar to those in the cohort achieving MRD negativity after both the first and the third cycles of consolidation and receiving allo-HSCT. MRD negativity after the first cycle of consolidation was a predictor for better outcome in adults with Ph(-) ALL in high-risk. The survival advantage of the allo-HSCT cohort was not pronounced compared with that in the chemotherapy cohort even in those with high-risk features but achieving MDR negativity after both the first and third cycles of consolidation. However, allo-HSCT could be a good option for the patients with MRD positivity after the first and/or the third cycle of consolidation.
探讨微小残留病（MRD）在预测高危费城染色体阴性成人急性淋巴细胞白血病（Ph(-) ALL）预后及指导治疗中的意义。回顾性分析初诊高危Ph(-) ALL且达到完全缓解（CR）的成人患者资料。通过COX回归模型和地标性分析确定与预后相关的变量。本研究共纳入177例患者，其中99例（56%）为男性，中位年龄40岁（范围16 - 65岁）。其中，95例（54%）患者在CR1期接受了异基因造血干细胞移植（allo-HSCT）。多因素分析显示，巩固治疗第一周期后MRD阴性（=0.52，95% 0.30 - 0.89，=0.017）以及在4周内达到CR（=0.43，95% 0.24 - 0.79，=0.006）是与更长无病生存期（DFS）显著相关的因素，allo-HSCT与更长的DFS（=0.13，95% 0.08 - 0.22，<0.001）和总生存期（OS）（=0.24，95% 0.15 - 0.41，<0.001）均相关。对121例患者进行地标性分析，在85例巩固治疗第一周期后达到MRD阴性的患者中，多因素分析显示巩固治疗第三周期后MRD阴性与更长的DFS（=0.18，95% 0.05 - 0.64，=0.008）和OS（=0.14，95% 0.04 - 0.50，=0.003）显著相关。对于巩固治疗第一周期和第三周期后均达到MRD阴性的患者，allo-HSCT队列的3年DFS率与化疗队列相比有更高趋势（75.2% 51.3%，=0.082），然而，两个队列的3年OS率相似（72.7% 68.7%，=0.992）。在巩固治疗第一周期和/或第三周期后MRD阳性的患者中，allo-HSCT队列的3年DFS（64.8% 33.3%，=0.006）和OS（77.0% 33.3%，=0.028）率显著高于化疗队列，且与巩固治疗第一周期和第三周期后均达到MRD阴性并接受allo-HSCT的队列相似。巩固治疗第一周期后MRD阴性是高危Ph(-) ALL成人患者预后较好的预测指标。即使在具有高危特征但巩固治疗第一周期和第三周期后均达到MRD阴性的患者中，allo-HSCT队列与化疗队列相比生存优势并不明显。然而，对于巩固治疗第一周期和/或第三周期后MRD阳性的患者，allo-HSCT可能是一个较好的选择。
