State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China; National Clinical Research Center for Blood Disease, Tianjin, China; Leukemia Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
National Clinical Research Center for Blood Disease, Tianjin, China.
Exp Hematol. 2021 Apr;96:63-72.e3. doi: 10.1016/j.exphem.2021.01.007. Epub 2021 Jan 29.
Minimal residual disease (MRD) levels monitored by polymerase chain reaction are associated with outcomes in acute myeloid leukemia with RUNX1-RUNX1T1. The objectives of our study were to quantitatively compare the predictive value of MRD reduction and absolute copies and assess the influence of other prognostic factors on MRD. A total of 224 consecutive patients with RUNX1-RUNX1T1 aged ≤55 years were included in the MRD study. Patients received different induction regimens including conventional- or intermediate-dose cytarabine plus low-dose daunorubicin and omacetaxine mepesuccinate or daunorubicin at 60 mg/m/day on days 1-3. As continuous variables, both MRD reduction and absolute MRD level were significantly associated with cumulative incidence of relapse (CIR; hazard ratio [HR] = 1.610, 95% confidence interval [CI]: 1.370-1.890, p < 0.001, and HR = 1.170, 95% CI: 1.120-1.230, p < 0.001, respectively). For the CIR, the area under the curves (AUCs) of MRD reduction and absolute MRD level after the first consolidation chemotherapy were 0.629 and 0.629, respectively. Intermediate-dose cytarabine induction (HR = 0.494; p = 0.039 for CIR, HR, 0.451; p = 0.014 for RFS, and HR, 0.262; p = 0.006 for OS) remained significantly associated with outcomes after adjusting for MRD reduction after the first consolidation therapy (HR = 1.456, p < 0.001, for CIR; HR = 1.467, p = 0.001, for relapse-free survival; and HR = 1.468, p = 0.014, for overall survival) in multivariate analyses. In conclusion, the prognostic significance of MRD after the first consolidation therapy was influenced by the induction regimen in acute myeloid leukemia with RUNX1-RUNX1T1.
通过聚合酶链反应监测微小残留病 (MRD) 水平与 RUNX1-RUNX1T1 急性髓系白血病的结果相关。我们研究的目的是定量比较 MRD 减少和绝对拷贝的预测价值，并评估其他预后因素对 MRD 的影响。共有 224 例年龄≤55 岁的 RUNX1-RUNX1T1 患者纳入 MRD 研究。患者接受不同的诱导方案，包括常规或中剂量阿糖胞苷联合低剂量柔红霉素和奥马曲星甲磺酸盐或柔红霉素 60mg/m/天，第 1-3 天。作为连续变量，MRD 减少和绝对 MRD 水平与累积复发率 (CIR; 风险比 [HR] = 1.610, 95%置信区间 [CI]: 1.370-1.890, p < 0.001 和 HR = 1.170, 95% CI: 1.120-1.230, p < 0.001) 显著相关。对于 CIR，第一次巩固化疗后 MRD 减少和绝对 MRD 水平的曲线下面积 (AUC) 分别为 0.629 和 0.629。中剂量阿糖胞苷诱导 (HR = 0.494; p = 0.039 用于 CIR，HR = 0.451; p = 0.014 用于 RFS，和 HR = 0.262; p = 0.006 用于 OS) 在调整第一次巩固治疗后 MRD 减少后，与结局仍显著相关 (HR = 1.456, p < 0.001 用于 CIR; HR = 1.467, p = 0.001 用于无复发生存率；和 HR = 1.468, p = 0.014 用于总生存) 在多变量分析中。总之，急性髓系白血病中 RUNX1-RUNX1T1 患者第一次巩固治疗后 MRD 的预后意义受诱导方案的影响。
