Wang Yu, Xue Yu-Juan, Jia Yue-Ping, Zuo Ying-Xi, Lu Ai-Dong, Zhang Le-Ping
Department of Pediatrics, Peking University People's Hospital, Peking University, Beijing, China.
Front Oncol. 2021 Feb 5;10:596677. doi: 10.3389/fonc.2020.596677. eCollection 2020.
While the role of minimal residual disease (MRD) assessment and the significance of achieving an MRD-negative status during treatment have been evaluated in previous studies, there is limited evidence on the significance of MRD re-emergence without morphological relapse in acute lymphoblastic leukemia (ALL). We sought to determine the clinical significance of MRD re-emergence in pediatric ALL patients.
Between 2005 and 2017, this study recruited 1126 consecutive patients newly diagnosed with ALL. Flow cytometry was performed to monitor MRD occurrence during treatment.
Of 1030 patients with MRD-negative results, 150 (14.6%) showed MRD re-emergence while still on morphological complete remission (CR). Patients with white blood cell counts of ≥50 × 10/L ( = 0.033) and MRD levels of ≥0.1% on day 33 ( = 0.012) tended to experience MRD re-emergence. The median re-emergent MRD level was 0.12% (range, 0.01-10.00%), and the median time to MRD re-emergence was 11 months (range, <1-52 months). Eighty-five (56.6%) patients subsequently developed relapse after a median of 4.1 months from detection of MRD re-emergence. The median re-emergent MRD level was significantly higher in the relapsed cohort than in the cohort with persistent CR (1.05% vs. 0.48%, = 0.005). Of the 150 patients, 113 continued to receive chemotherapy and 37 underwent transplantation. The transplantation group demonstrated a significantly higher 2-year overall survival (88.7 ± 5.3% vs. 46.3 ± 4.8%, 0.001) and cumulative incidence of relapse (23.3 ± 7.4% vs. 64.0 ± 4.6%, 0.001) than the chemotherapy group.
MRD re-emergence during treatment was associated with an adverse outcome in pediatric ALL patients. Transplantation could result in a significant survival advantage for these patients.
虽然既往研究已评估了微小残留病（MRD）评估的作用以及治疗期间达到MRD阴性状态的意义，但关于急性淋巴细胞白血病（ALL）中无形态学复发的MRD再次出现的意义的证据有限。我们试图确定MRD再次出现在儿童ALL患者中的临床意义。
2005年至2017年期间，本研究招募了1126例新诊断为ALL的连续患者。在治疗期间进行流式细胞术以监测MRD的发生情况。
在1030例MRD阴性结果的患者中，150例（14.6%）在仍处于形态学完全缓解（CR）时出现了MRD再次出现。白细胞计数≥50×10⁹/L（P = 0.033）且第33天MRD水平≥0.1%（P = 0.012）的患者倾向于出现MRD再次出现。再次出现的MRD水平中位数为0.12%（范围，0.01 - 10.00%），MRD再次出现的中位时间为11个月（范围，<1 - 52个月）。其中85例（56.6%）患者在检测到MRD再次出现后中位4.1个月后随后复发。复发队列中再次出现的MRD水平中位数显著高于持续CR队列（1.05%对0.48%，P = 0.005）。在这150例患者中，113例继续接受化疗，37例接受了移植。移植组的2年总生存率（88.7±5.3%对46.3±4.8%，P = 0.001）和累积复发率（23.3±7.4%对64.0±4.6%，P = 0.001）均显著高于化疗组。
治疗期间MRD再次出现与儿童ALL患者的不良预后相关。移植可为这些患者带来显著的生存优势。
