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Leukemia-associated immunophenotypes subdivided in "categories of specificity" improve the sensitivity of minimal residual disease in predicting relapse in acute myeloid leukemia.
Cytometry Part B: Clinical Cytometry ( IF 2.3 ) Pub Date : 2019-11-07 , DOI: 10.1002/cyto.b.21855
Giovanni Rossi 1 , Vincenzo Giambra 2 , Maria M Minervini 1 , Chiara De Waure 3 , Silvia Mancinelli 3 , Michele Ciavarella 2 , Nicola P Sinisi 1 , Potito R Scalzulli 1 , Angelo M Carella 1 , Nicola Cascavilla 1
Affiliation  

BACKGROUND The assessment of minimal residual disease (MRD) by flow cytometry (FC) has a prognostic impact in acute myeloid leukemia (AML), despite the low sensitivity in predicting relapse. Nonetheless, the role of leukemic-associated immunophenotypes (LAIPs)-related specificity on the sensitivity of MRD has not been clarified yet. In this respect, we accomplished this study. METHODS LAIP-frequencies of bone marrow samples from healthy donors and patients after treatment were quantified and subdivided in "categories of specificity" named as: "strong," "good," and "weak." At the following, the diagnostic performance of MRD was investigated in terms of sensitivity, specificity, predictive values, likelihood ratio (LR). RESULTS "Strong" LAIPs were identified by CD7, CD2, CD4, and CD56 markers while "weak" LAIPs, independently of coexpressed markers, were mainly observed in CD33+ cells. MRD identified patients with significantly low DFS and OS but showed a low sensitivity in predicting relapse. Interestingly, majority of recurrences was noticed in patients with two LAIPs and lacking of "strong" LAIPs or only with one "good" LAIP. Thus, only patients showing one "strong" or two "good" LAIPs were considered suitable for MRD monitoring and selected to be further investigated. In this subset, positive MRD predicted a poor prognosis. Moreover, a higher sensitivity, negative predictive value (NPV) and LR- were observed after comparison with the previous series. CONCLUSIONS These data highlight the relevant role of LAIP classification in "categories of specificity" in improving the sensitivity of MRD as assessed by FC.

中文翻译:

细分为“特异性类别”的与白血病相关的免疫表型提高了最小残留疾病在预测急性髓细胞性白血病复发中的敏感性。

背景技术尽管预测复发的敏感性较低,但通过流式细胞术(FC)评估最小残留疾病(MRD)对急性髓细胞性白血病(AML)的预后有影响。然而,白血病相关免疫表型(LAIPs)相关特异性在MRD敏感性中的作用尚未阐明。在这方面,我们完成了这项研究。方法对来自健康供体和治疗后患者的骨髓样品的LAIP频率进行定量,并细分为“特异性”,分别为“强”,“好”和“弱”。接下来,就敏感性,特异性,预测值,似然比(LR)方面对MRD的诊断性能进行了研究。结果通过CD7,CD2,CD4,CD56和CD56标记,而“弱” LAIP则独立于共表达标记,主要在CD33 +细胞中观察到。MRD确定了DFS和OS明显较低的患者,但预测复发的敏感性较低。有趣的是,大多数复发是在患有两个LAIP且缺乏“强” LAIP或仅伴有一个“好” LAIP的患者中发现的。因此,只有表现出一个“强”或两个“好” LAIP的患者才被认为适合MRD监测,并被选择进行进一步研究。在这一亚组中,MRD阳性预后不良。此外,与以前的系列比较后,观察到更高的灵敏度,阴性预测值(NPV)和LR-。结论这些数据强调了LAIP分类在“特异性分类”中的相关作用。
更新日期:2019-11-07
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