Shi Xiao-lan, Tang Xiao-wen, Wei Xiao-ai, Zhao Bing-rui, Zhou Qian-lan, Ye Fan, Lu Yu-xia, Sun Xing-wei, Zhu Ming-qing, Shen Wen-hong, Qiu Hui-ying, Sun Ai-ning, Wu De-pei
Department of Hematology, First Affiliated Hospital, Soochow University, Jiangsu Institute of Hematology; Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou 215006, China.
Zhonghua Yi Xue Za Zhi. 2011 Oct 18;91(38):2692-6.
To explore the relationship between minimal residual disease (MRD) and the outcome of patients with high-risk acute leukemia (AL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT).
By 4/5-color multi-parameter flow cytometry (MFC, CD45/SSC gating) for detecting MRD at pre-(day-30) and post-transplant (day +30, +60, +100, 6 months, 9 months and 12 months), the investigators retrospectively analyzed the MRD levels and the prognosis of 90 high-risk patients. According to the MRD cutoff value of 0.1%, the low-level and high-level groups were defined. In the high-level group, the patients were divided into two sub groups according to the subsequent treatment (intervention therapy group and non-intervention therapy group).
MRD pre-transplant had no predictive value for the clinical outcome. The patients with high levels of MRD post-transplant (+60 d and +100 d) showed higher relapse rates than those of the low-level group. In addition, regarding MRD +100 d post-transplant, differences were significant among 3 groups (high-level MRD and intervention therapy group, high-level MRD and non-intervention therapy group and low-level MRD group) including 1-year relapse-free survival (RFS) (100% vs 60.87% vs 91.30%, P < 0.05) and 3-year RFS (85.71% vs 44.72% vs 68.48%, P < 0.05). The median time from first high level MRD detected to clinical relapse was 2.5 (1 - 26) months. In the high level MRD group (+100 d post-transplant), 7 of 30 patients received intervention therapy without relapse. However another 23 patients had no intervention treatment and 11 of them relapsed latter (P < 0.05).
The MFC-based quantification of MRD post-transplant reveals important prognostic information in patients with high-risk AL. MRD check point at day +100 (cutoff: 0.1%) may discriminate different risk populations. Those patients with MRD levels ≥ 0.1% should receive early intervention at an early stage and a low tumor burden so as to reduce the relapse rate and boost survival.
探讨微小残留病（MRD）与接受异基因造血干细胞移植（HSCT）的高危急性白血病（AL）患者预后的关系。
通过4/5色多参数流式细胞术（MFC，CD45/SSC设门）在移植前（第30天）和移植后（第30、60、100天，6个月、9个月和12个月）检测MRD，研究者回顾性分析了90例高危患者的MRD水平及预后。根据MRD临界值0.1%，定义低水平组和高水平组。在高水平组中，根据后续治疗将患者分为两个亚组（干预治疗组和非干预治疗组）。
移植前MRD对临床结局无预测价值。移植后（第60天和第100天）MRD水平高的患者复发率高于低水平组。此外，关于移植后第100天的MRD，三组（高水平MRD与干预治疗组、高水平MRD与非干预治疗组和低水平MRD组）之间的差异具有统计学意义，包括1年无复发生存率（RFS）（100%对60.87%对91.30%，P<0.05）和3年RFS（85.71%对44.72%对68.48%，P<0.05）。从首次检测到高水平MRD至临床复发的中位时间为2.5（1 - 26）个月。在高水平MRD组（移植后第100天），30例患者中有7例接受干预治疗且未复发。然而，另外23例患者未接受干预治疗，其中11例随后复发（P<0.05）。
基于MFC对移植后MRD进行定量分析可揭示高危AL患者的重要预后信息。移植后第100天的MRD检查点（临界值：0.1%）可区分不同风险人群。那些MRD水平≥0.1%的患者应在早期且肿瘤负荷较低时接受早期干预，以降低复发率并提高生存率。
