Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Am J Hematol. 2020 Feb;95(2):144-150. doi: 10.1002/ajh.25671. Epub 2019 Nov 19.
The minimal or measurable residual disease (MRD) status following induction/consolidation chemotherapy is an important prognostic endpoint in adult patients with newly diagnosed acute lymphoblastic leukemia (ALL). However, the optimal time-point (TP) of MRD assessment and its impact on outcome remains unclear. We analyzed 215 patients with newly diagnosed Philadelphia negative B-cell ALL who received intensive chemotherapy, and had available MRD assessment by multicolor flow cytometry at two separate TPs. The median time to first TP (1TP) and second TP (2TP) were 24 and 110 days, respectively. At 1TP, 148 patients (68%) were MRD negative and 67 (32%) were positive. Of the 148 patients with negative MRD at 1TP, 147 (99%) maintained it through 2TP. Patients who were MRD negative at both TPs, early MRD responders, had the 3-year event-free survival (EFS), and overall survival (OS) rates of 65% and 76%, respectively. Patients with improved MRD status from positive to negative, late MRD responders, had lower 3-year EFS and OS rates, 42% and 58%, respectively (P = .001). Multivariate analysis showed that KMT2A (MLL) rearrangement and MRD positivity at 1TP were the only factors correlated with worse OS. In conclusion, the earlier achievement of MRD negative remission is a stronger prognostic factor for survival.
在新诊断的成人急性淋巴细胞白血病（ALL）患者中，诱导/巩固化疗后微小残留病（MRD）状态是一个重要的预后终点。然而，MRD 评估的最佳时间点（TP）及其对结局的影响仍不清楚。我们分析了 215 例新诊断的费城染色体阴性 B 细胞 ALL 患者，他们接受了强化化疗，并在两个单独的 TP 点通过多色流式细胞术进行了可评估的 MRD。首次 TP（1TP）和第二次 TP（2TP）的中位时间分别为 24 天和 110 天。在 1TP 时，148 例患者（68%）MRD 阴性，67 例（32%）MRD 阳性。在 1TP 时，148 例 MRD 阴性患者中有 147 例（99%）通过 2TP 维持 MRD 阴性。在两个 TP 时均为 MRD 阴性的患者，早期 MRD 应答者，3 年无事件生存率（EFS）和总生存率（OS）分别为 65%和 76%。MRD 状态从阳性转为阴性的患者，晚期 MRD 应答者，3 年 EFS 和 OS 率分别为 42%和 58%（P =.001）。多变量分析表明，KMT2A（MLL）重排和 1TP 时的 MRD 阳性是与 OS 较差相关的唯一因素。总之，更早实现 MRD 阴性缓解是生存的一个更强的预后因素。
