Multilineage Dysplasia as Assessed by Immunophenotype in Acute Myeloid Leukemia: A Prognostic Tool in a Genetically Undefined Category.
Multilineage Dysplasia as Assessed by Immunophenotype in Acute Myeloid Leukemia: A Prognostic Tool in a Genetically Undefined Category.
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DOI：
10.3390/cancers12113196
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发表时间：
2020-10-30
期刊：
影响因子：
5.2
通讯作者：
Bosi A
中科院分区：
文献类型：
--
作者：
Mannelli F;Bencini S;Piccini M;Gianfaldoni G;Bonetti MI;Peruzzi B;Caporale R;Scappini B;Pancani F;Ponziani V;Signori L;Zizza M;Annunziato F;Bosi A
多谱系不典型增生在急性髓系白血病中的预后作用仍存在争议。我们工作的目的是通过替代传统形态学方法的技术（多参数流式细胞术）来研究发育不良。为此，我们使用了免疫表型评分（IPS），能够通过在对照组中获得的与正常轮廓的偏差程度来估计发育不良。当整体考虑或在明确定义的遗传类别内考虑时，IPS 无法提供对预后的深入了解。有趣的是，当我们关注基因不确定的 NPM1、FLT3 和 CEBPA 三阴性患者时，IPS 相关的发育不良传达了重要的预后信息。这一类别仍然代表着不可忽视的一部分患者，他们缺乏靶向药物或适当风险评估的特定分子特征。在这种背景下，我们的数据可以帮助解决治疗策略中相对未满足的需求，并为快速发展的 AML 治疗场景中的反应预测提供见解。世界卫生组织 (WHO) 的髓系肿瘤分类将“伴有骨髓增生异常相关变化 (MRC)”的急性髓系白血病 (AML) 视为一个单独的实体。虽然记忆记忆和细胞遗传学标准为这一亚群提供了客观的归因，并具有明显的不利预后意义，但通过形态学评估的多谱系不典型增生 (MLD) 的实际作用仍存在争议。我们工作的目的是通过形态学的替代技术，即多参数流式细胞术 (MFC)，在我们中心接受强化治疗的 302 名 AML 患者中研究 MLD。我们在未选择的分析中观察到的与形态的相关性重申了基于 MFC 的方法突出不典型增生的能力。通过免疫表型评分 (IPS) 估计的 MLD 数据在整体考虑或在明确定义的遗传类别中无法提供对预后的深入了解。有趣的是，当我们关注基因不确定的 NPM1、FLT3 和 CEBPA 三阴性 (TN-AML) 患者时，IPS 相关的发育不良传达了重要的预后信息。在这种情况下，与在一种或两种（中性粒细胞和红系）细胞谱系中表现出发育不良的患者相比，缺乏发育不良特征（IPS_0）与显着更高的 CR 率和更长的生存期相关。在同种异体 HSCT 审查和包括基线和治疗相关协变量的多变量分析中，IPS 类别的影响保持了其有效性。在缺乏遗传决定因素的亚组中，我们的数据可以帮助解决风险评估和治疗策略方面相对未满足的需求，并为快速发展的 AML 治疗方案中的反应预测提供见解。
The prognostic role of multi-lineage dysplasia is still debated in acute myeloid leukemia. The aim of our work was to study dysplasia by a technique alternative to the conventional morphological method, which is multi-parameter flow cytometry. To this end, we used an immune-phenotypic score (IPS), able to estimate dysplasia by the extent of deviation from normal profile, obtained in a control group. IPS provided no insight into prognosis when considered overall nor within well-defined genetic categories. Of interest, IPS-related dysplasia conveyed significant prognostic information when we focused on genetically undefined patients, triple-negative for NPM1, FLT3 and CEBPA. This category still represents a non-negligible fraction of patients, that lack specific molecular features either for targeted drugs or for proper risk assessment. In this context, our data could help address the relative unmet needs in treatment strategy, and provide insight into response prediction in the rapidly evolving therapeutic scenario of AML. Acute myeloid leukemia (AML) “with myelodysplasia-related changes (MRC)” is considered a separate entity by the World Health Organization (WHO) classification of myeloid neoplasms. While anamnestic and cytogenetic criteria provide objective attribution to this subset, with clear unfavorable prognostic significance, the actual role of multi-lineage dysplasia (MLD) as assessed by morphology is debated. The aim of our work was to study MLD by a technique alternative to morphology, which is multiparameter flow cytometry (MFC), in a large series of 302 AML patients intensively treated at our Center. The correlation with morphology we observed in the unselected analysis reiterated the capability of the MFC-based approach at highlighting dysplasia. MLD data, estimated through an immune-phenotypic score (IPS), provided no insight into prognosis when considered overall nor within well-defined genetic categories. Of interest, IPS-related dysplasia conveyed significant prognostic information when we focused on genetically undefined patients, triple-negative for NPM1, FLT3 and CEBPA (TN-AML). In this context, the lack of dysplastic features (IPS_0) correlated with a significantly higher CR rate and longer survival compared to patients showing dysplasia in one or both (neutrophil and erythroid) cell lineages. The impact of IPS category maintained its validity after censoring at allogeneic HSCT and in a multivariate analysis including baseline and treatment-related covariates. In a subgroup featured by the lack of genetic determinants, our data could help address the relative unmet needs in terms of risk assessment and treatment strategy, and provide insight into prediction of response in the rapidly evolving therapeutic scenario of AML.
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影响因子：
158.5
作者：
Falini, B;Mecucci, C;Martelli, MF
通讯作者：
Martelli, MF
急性髓样白血病患者中添加了gemtuzumab ozogamicin将其诱导化疗：从随机对照试验中对单个患者数据的荟萃分析。
DOI：
10.1016/s1470-2045(14)70281-5
发表时间：
2014-08
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Hills RK;Castaigne S;Appelbaum FR;Delaunay J;Petersdorf S;Othus M;Estey EH;Dombret H;Chevret S;Ifrah N;Cahn JY;Récher C;Chilton L;Moorman AV;Burnett AK
通讯作者：
Burnett AK
影响因子：
10.1
作者：
Mannelli F;Ponziani V;Bencini S;Bonetti MI;Benelli M;Cutini I;Gianfaldoni G;Scappini B;Pancani F;Piccini M;Rondelli T;Caporale R;Gelli AM;Peruzzi B;Chiarini M;Borlenghi E;Spinelli O;Giupponi D;Zanghì P;Bassan R;Rambaldi A;Rossi G;Bosi A
通讯作者：
Bosi A
影响因子：
20.3
作者：
Kottaridis, PD;Gale, RE;Linch, DC
通讯作者：
Linch, DC
影响因子：
20.3
作者：
Miesner, Miriam;Haferlach, Claudia;Haferlach, Torsten
通讯作者：
Haferlach, Torsten