Rossi Giovanni, Minervini Maria Marta, Melillo Lorella, di Nardo Francesco, de Waure Chiara, Scalzulli Potito Rosario, Perla Gianni, Valente Daniela, Sinisi Nicola, Cascavilla Nicola
Department of Hematology and Stem Cell Transplant Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, v.le Cappuccini 1, 71013, San Giovanni Rotondo, Italy,
Ann Hematol. 2014 Jul;93(7):1149-57. doi: 10.1007/s00277-014-2029-9. Epub 2014 Feb 20.
In acute myeloid leukemia (AML), the detection of minimal residual disease (MRD) as well as the degree of log clearance similarly identifies patients with poor prognosis. No comparison was provided between the two approaches in order to identify the best one to monitor follow-up patients. In this study, MRD and clearance were assessed by both multiparameter flow cytometry (MFC) and WT1 expression at different time points on 45 AML patients achieving complete remission. Our results by WT1 expression showed that log clearance lower than 1.96 after induction predicted the recurrence better than MRD higher than 77.0 copies WT1/10(4) ABL. Conversely, on MFC, MRD higher than 0.2 % after consolidation was more predictive than log clearance below 2.64. At univariate and multivariate analysis, positive MRD values and log clearance below the optimal cutoffs were associated with a shorter disease-free survival (DFS). At the univariate analysis, positive MRD values were also associated with overall survival (OS). Therefore, post-induction log clearance by WT1 and post-consolidation MRD by MFC represented the most informative approaches to identify the relapse. At the optimal timing of assessment, positive MRD and log-clearance values lower than calculated thresholds similarly predicted an adverse prognosis in AML.
在急性髓系白血病(AML)中,微小残留病(MRD)的检测以及对数清除程度同样可识别出预后不良的患者。为了确定监测随访患者的最佳方法,未对这两种方法进行比较。在本研究中,对45例达到完全缓解的AML患者在不同时间点通过多参数流式细胞术(MFC)和WT1表达评估MRD和清除情况。我们通过WT1表达得出的结果显示,诱导后对数清除低于1.96比WT1/10⁴ABL高于77.0拷贝的MRD能更好地预测复发。相反,在MFC检测中,巩固治疗后MRD高于0.2%比对数清除低于2.64更具预测性。在单变量和多变量分析中,MRD阳性值和对数清除低于最佳临界值与无病生存期(DFS)较短相关。在单变量分析中,MRD阳性值也与总生存期(OS)相关。因此,诱导后通过WT1检测的对数清除和巩固治疗后通过MFC检测的MRD是识别复发最具信息量的方法。在最佳评估时机,MRD阳性和对数清除值低于计算阈值同样预示着AML患者预后不良。