Friederike Pastore, Annika Dufour, Tobias Benthaus, Klaus H. Metzeler, Stephanie Schneider, Bianka Ksienzyk, Gudrun Mellert, Evelyn Zellmeier, Purvi M. Kakadia, Michael Unterhalt, Wolfgang Hiddemann, Stefan K. Bohlander, Karsten Spiekermann, and Eva Hoster, University Hospital Munich Großhadern; Friederike Pastore, Klaus H. Metzeler, Wolfgang Hiddemann, Stefan K. Bohlander, and Karsten Spiekermann, Helmholtz Center Munich; Eva Hoster, University of Munich, Munich; Purvi M. Kakadia and Stefan K. Bohlander, University Hospital Marburg, Marburg; Michaela Feuring-Buske, University Hospital Ulm; Christian Buske, Comprehensive Cancer Center Ulm, University of Ulm, Ulm; Jan Braess, Klinikum Barmherzige Brüder, Regensburg; Maria Cristina Sauerland and Achim Heinecke, University of Muenster; Utz Krug, Wolfgang E. Berdel, and Thomas Buechner, University Hospital Muenster, Muenster; Bernhard Woermann, German Society of Hematology and Oncology, Berlin, Germany; Kati S. Maharry, Guido Marcucci, and Clara D. Bloomfield, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Kati S. Maharry, Mayo Clinic, Rochester, MN; and Stefan K. Bohlander, University of Auckland, Auckland, New Zealand.
J Clin Oncol. 2014 May 20;32(15):1586-94. doi: 10.1200/JCO.2013.52.3480. Epub 2014 Apr 7.
Cytogenetically normal (CN) acute myeloid leukemia (AML) is the largest and most heterogeneous cytogenetic AML subgroup. For the practicing clinician, it is difficult to summarize the prognostic information of the growing number of clinical and molecular markers. Our purpose was to develop a widely applicable prognostic model by combining well-established pretreatment patient and disease characteristics.
Two prognostic indices for CN-AML (PINA), one regarding overall survival (OS; PINAOS) and the other regarding relapse-free survival (RFS; PINARFS), were derived from data of 572 patients with CN-AML treated within the AML Cooperative Group 99 study (www.aml-score.org).
On the basis of age (median, 60 years; range, 17 to 85 years), performance status, WBC count, and mutation status of NPM1, CEBPA, and FLT3-internal tandem duplication, patients were classified into the following three risk groups according to PINAOS and PINARFS: 29% of all patients and 32% of 381 responding patients had low-risk disease (5-year OS, 74%; 5-year RFS, 55%); 56% of all patients and 39% of responding patients had intermediate-risk disease (5-year OS, 28%; 5-year RFS, 27%), and 15% of all patients and 29% of responding patients had high-risk disease (5-year OS, 3%; 5-year RFS, 5%), respectively. PINAOS and PINARFS stratified outcome within European LeukemiaNet genetic groups. Both indices were confirmed on independent data from Cancer and Leukemia Group B/Alliance trials.
We have developed and validated, to our knowledge, the first prognostic indices specifically designed for adult patients of all ages with CN-AML that combine well-established molecular and clinical variables and that are easily applicable in routine clinical care. The integration of both clinical and molecular markers could provide a basis for individualized patient care through risk-adapted therapy of CN-AML.
核型正常（CN）急性髓系白血病（AML）是最大且异质性最大的细胞遗传学 AML 亚组。对于临床医生而言，很难总结越来越多的临床和分子标志物的预后信息。我们的目的是通过结合成熟的治疗前患者和疾病特征，开发一种广泛适用的预后模型。
从接受 AML 协作组 99 研究（www.aml-score.org）治疗的 572 例 CN-AML 患者的数据中，得出了两个 CN-AML 的预后指标（PINA），一个是总生存期（OS；PINAOS），另一个是无复发生存期（RFS；PINARFS）。
根据年龄（中位数，60 岁；范围，17 至 85 岁）、表现状态、白细胞计数以及 NPM1、CEBPA 和 FLT3 内部串联重复突变状态，根据 PINAOS 和 PINARFS，患者被分为以下三个风险组：所有患者中有 29%，且 381 例有反应的患者中有 32%为低危疾病（5 年 OS，74%；5 年 RFS，55%）；所有患者中有 56%，且 39%的有反应的患者为中危疾病（5 年 OS，28%；5 年 RFS，27%），所有患者中有 15%，且 29%的有反应的患者为高危疾病（5 年 OS，3%；5 年 RFS，5%）。PINAOS 和 PINARFS 在欧洲白血病网遗传组内对结局进行分层。这两个指标都在癌症和白血病组 B/联盟试验的独立数据中得到了验证。
据我们所知，我们已经开发并验证了第一个专为所有年龄的 CN-AML 成年患者设计的预后指标，该指标结合了成熟的分子和临床变量，并且易于在常规临床护理中应用。整合临床和分子标志物可以为通过适应性治疗 CN-AML 为患者提供个体化的护理提供基础。
