Department of Laboratory Hematology, University Health Network, University of Toronto, Toronto, Canada.
Department of Clinical Laboratory Genetics, Genome Diagnostics, University Health Network, Canada.
Hum Pathol. 2020 Oct;104:117-126. doi: 10.1016/j.humpath.2020.08.003. Epub 2020 Aug 13.
Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) generally confers poor prognosis; however, the clinical outcome remains heterogeneous. We sought to further stratify this subentity of AML by performing a retrospective analysis of 179 adult patients with AML-MRC diagnosed at our institution. Based on 2016 World Health Organization diagnostic criteria, 44 (25%) patients had multilineage dysplasia alone (AML-MRC-M), 74 (41%) had history of myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative disease (AML-MRC-H), and 61 (34%) had MDS-related cytogenetics (AML-MRC-C). AML-MRC-M and hematopoietic stem cell transplantation (HSCT) were associated with prolonged event-free survival (EFS) (P = 0.0051 and P < 0.0001, respectively) and overall survival (OS) (P = 0.0015 and P < 0.0001, respectively), whereas AML-MRC-C and age ≥60 years were associated with shorter EFS (P = 0.028 and P = 0.015, respectively) and OS (P = 0.021 and P = 0.013, respectively). Of note, NPM1 did not affect the patient's outcome. Multivariable analysis confirmed HSCT and AML-MRC-C as independent predictors for EFS (P < 0.0001 and P = 0.0342, respectively) and OS (P < 0.0001 and P = 0.0295, respectively). AML-MRC-M was an independent predictor for OS (P = 0.0449). When compared with a control group of 105 patients with normal karyotype AML not otherwise specified (NK-AML-NOS), patients with AML-MRC-M had similar EFS and OS (P = 0.99 and P = 0.91, respectively). However, AML-MRC-H and AML-MRC-C were associated with shorter EFS and OS (P = 0.0002 and P < 0.0001, respectively) than the same control group. In a subset of patients, next-generation sequencing analysis showed AML-MRC-M was associated with ASXL1 mutation compared with NK-AML (56% vs 6%). In conclusion, AML-MRC-M demonstrates a superior clinical outcome compared with the rest of the AML-MRC group. They have comparable outcomes to NK-AML-NOS, and these data suggest AML-MRC-M may be considered not to be classified in the same group as patients with other AML-MRC.
伴骨髓增生异常相关改变的急性髓系白血病（AML-MRC）通常预后不良；然而，其临床结果仍然存在异质性。我们通过对在我院诊断为 AML-MRC 的 179 例成年患者进行回顾性分析，旨在进一步对该 AML 亚群进行分层。根据 2016 年世界卫生组织诊断标准，44 例（25%）患者仅有多系发育不良（AML-MRC-M），74 例（41%）有骨髓增生异常综合征（MDS）或骨髓增生异常/骨髓增生性疾病（AML-MRC-H）病史，61 例（34%）有 MDS 相关细胞遗传学改变（AML-MRC-C）。AML-MRC-M 和造血干细胞移植（HSCT）与延长的无事件生存（EFS）（P=0.0051 和 P<0.0001）和总生存（OS）（P=0.0015 和 P<0.0001）相关，而 AML-MRC-C 和年龄≥60 岁与更短的 EFS（P=0.028 和 P=0.015）和 OS（P=0.021 和 P=0.013）相关。值得注意的是，NPM1 不影响患者的预后。多变量分析证实 HSCT 和 AML-MRC-C 是 EFS（P<0.0001 和 P=0.0342）和 OS（P<0.0001 和 P=0.0295）的独立预测因素。AML-MRC-M 是 OS 的独立预测因素（P=0.0449）。与一组 105 例核型正常的非特指急性髓系白血病（NK-AML-NOS）患者的对照组相比，AML-MRC-M 患者的 EFS 和 OS 相似（P=0.99 和 P=0.91）。然而，AML-MRC-H 和 AML-MRC-C 与较短的 EFS 和 OS（P=0.0002 和 P<0.0001）相关，与相同的对照组相比。在一组患者中，下一代测序分析显示 AML-MRC-M 与 NK-AML 相比，ASXL1 突变的发生率更高（56% vs 6%）。总之，AML-MRC-M 与 AML-MRC 组的其他患者相比，具有更优越的临床结果。它们与 NK-AML-NOS 的结局相当，这些数据表明 AML-MRC-M 可能不被认为与其他 AML-MRC 的患者归为同一组。
