Vidriales María-Belén, Pérez-López Estefanía, Pegenaute Carlota, Castellanos Marta, Pérez José-Juan, Chandía Mauricio, Díaz-Mediavilla Joaquín, Rayón Consuelo, de Las Heras Natalia, Fernández-Abellán Pascual, Cabezudo Miguel, de Coca Alfonso García, Alonso Jose M, Olivier Carmen, Hernández-Rivas Jesús M, Montesinos Pau, Fernández Rosa, García-Suárez Julio, García Magdalena, Sayas María-José, Paiva Bruno, González Marcos, Orfao Alberto, San Miguel Jesús F
Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain; Instituto de Biología Molecular y Celular del Cáncer (CIC-CSIC), Salamanca, Spain.
Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain.
Leuk Res. 2016 Jan;40:1-9. doi: 10.1016/j.leukres.2015.10.002. Epub 2015 Oct 22.
The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥ 0.1%; ≥ 0.01-0.1%; and <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p=0.002). Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p=0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics.
微小残留病(MRD)分析在急性髓系白血病(AML)中的临床应用尚未明确。我们使用多参数流式细胞术分析了306例非急性早幼粒细胞白血病(APL)AML患者诱导治疗完全缓解后MRD水平的预后影响。首先,我们验证了我们之前提出的MRD阈值(≥0.1%;≥0.01 - 0.1%;<0.01)的预后价值,5年无复发生存率(RFS)分别为38%、50%和71%(p = 0.002)。细胞遗传学是AML中最相关的预后因素,然而中等风险细胞遗传学代表了一个需要其他生物标志物进行风险分层的灰色区域,并且我们表明MRD评估可区分三个预后亚组(p = 0.03)。此外,MRD评估产生了关于有利和不利细胞遗传学的相关信息,因为具有有利细胞遗传学但MRD水平高的患者预后较差,而具有不利细胞遗传学但未检测到MRD的患者克服了不良预后。有趣的是,在MRD水平为中等或高的患者中,与化疗相比,强化移植改善了结局,而强化治疗类型并未影响MRD水平低的患者的结局。多变量分析显示年龄、MRD和细胞遗传学为独立变量。此外,基于MRD水平和细胞遗传学生成了一个在临床实践中易于使用的评分系统。