Wang Lulu, Chen Rongrong, Li Li, Zhu Lixia, Huang Xianbo, Ye Xiujin
Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, Zhejiang, China.
Program in Clinical Medicine, School of Medicine of Zhejiang University Hangzhou, Zhejiang, China.
Am J Cancer Res. 2022 May 15;12(5):2216-2225. eCollection 2022.
To investigate the prognostic implication of minimal residual disease (MRD) evaluation in chronic myelomonocytic leukemia (CMML), we conducted a restropective study included a total of 174 CMML patients in our hospital from January 2010 to March 2021. In which 50/174 (29%) bone marrow samples were conducted by multiparameter flow cytometry (FCM) assessed MRD analysis after the first three cycles of treatment and were included in this study. MRD was detected by six- to eight-colour FCM. The achievement of early MRD negativity had better clinical outcomes in patients with CMML, which fared better prognosis in terms of not only PFS (P=0.006) but also OS (P=0.02) after the first cycle, and PFS (P=0.023 and P=0.041) after the second and third cycles, whereas no significantly influence in OS. In addition, MRD negative after initial treatment remained its independent prognostic value associated with PFS (adjusted hazard ratio [HR] 0.161, 95 CI 0.035-0.738; P=0.019) and OS (adjusted HR 0.136; 95 CI 0.017-1.077; P=0.059), indicating that patients with MRD-negative after the initial treatment alone could obtain the greatest clinical benefit. According to MRD level, the patients were divided into 4 different groups: very low risk (fewer than 10 cells) in 15 cases, low risk (10 to 10 cells) in 6; and 6 were at intermediate risk (fewer than 10 to 10 cells). The rest of 23 patients were were assigned to the high-risk grades (more than 10 residual cells), we find this risk stratification model is significantly associated with better PFS (P=0.002) but marginal significantly associated with OS (P=0.068). Notably, patients with DNMT3A mutation fared a shorter PFS in the MRD positive subgroup (P=0.068). MRD is highly predictive of prognosis, and its combination with molecular profile may help identify patients at increased risk for progression to further improve the management of patients with CMML. Large-scaled investigations are warranted to validate our conclusions and its potential in clinical practice.
为了研究微小残留病（MRD）评估在慢性粒单核细胞白血病（CMML）中的预后意义，我们进行了一项回顾性研究，纳入了2010年1月至2021年3月期间我院共174例CMML患者。其中，50/174（29%）例骨髓样本在治疗的前三个周期后通过多参数流式细胞术（FCM）进行了MRD分析，并纳入本研究。通过六色至八色FCM检测MRD。CMML患者中早期MRD转阴具有更好的临床结局，在第一个周期后不仅无进展生存期（PFS，P=0.006）而且总生存期（OS，P=0.02）方面预后更好，在第二个和第三个周期后PFS方面（P=0.023和P=0.041）也是如此，而对OS无显著影响。此外，初始治疗后MRD阴性在PFS（调整后风险比[HR]0.161，95%置信区间0.035 - 0.738；P=0.019）和OS（调整后HR 0.136；95%置信区间0.017 - 1.077；P=0.059）方面仍具有独立的预后价值，表明仅初始治疗后MRD阴性的患者可获得最大的临床益处。根据MRD水平，将患者分为4个不同组：极低风险（少于10个细胞）15例，低风险（10至10个细胞）6例；中风险（少于10至10个细胞）6例。其余23例患者被归为高风险等级（多于10个残留细胞），我们发现这种风险分层模型与更好的PFS显著相关（P=0.002），但与OS边缘显著相关（P=0.068）。值得注意的是，DNMT3A突变患者在MRD阳性亚组中的PFS较短（P=0.068）。MRD对预后具有高度预测性，其与分子特征相结合可能有助于识别进展风险增加的患者，以进一步改善CMML患者的管理。有必要进行大规模研究以验证我们的结论及其在临床实践中的潜力。
