与治疗相关的AML：大量AML患者队列中长期预后分析（包括强化和非强化治疗）

Therapy-related AML: long-term outcome in a large cohort of AML-patients with intensive and non-intensive therapy

Blood Cancer Journal

影响因子:11.6

分区:医学1区 Top / 血液学1区肿瘤学1区

发表日期:2024 Sep 16

作者: Sophia Gross, Jana Ihlow, Leonie Busack, Kacper Adamiak, Jens Schrezenmeier, Julia Jesse, Michaela Schwarz, Anne Flörcken, Lam Giang Vuong, Kathrin Rieger, Jan Krönke, Philipp le Coutre, Vivien Boldt, Ann-Christin von Brünneck, David Horst, Thomas Burmeister, Igor-Wolfgang Blau, Ulrich Keller, Lars Bullinger, Jörg Westermann

DOI: 10.1038/s41408-024-01140-5

摘要

治疗相关急性髓系白血病（t-AML）常表现出不良（遗传）特征。关于t-AML对AML长期预后的影响，仍存在争议。因此，我们回顾性分析了1133例AML患者（其中225例t-AML，908例新发AML）的临床和生物学特征，随访中位数为81.8个月。t-AML患者表现出更多的不良遗传变异、更高的年龄及更多合并症。强化治疗的t-AML患者中位总生存期为13.7个月，而新发AML为39.4个月（p < 0.001）。非强化治疗中，两组生存期无显著差异（p = 0.394）。在强化治疗组中，ELN中级I/II（p = 0.009）和不良（p = 0.016）风险组中，t-AML组明显劣于新发AML，但在有利风险组（APL p = 0.927，ELN有利 p = 0.714）中无差异。多变量分析显示，t-AML并非OS（p = 0.103）、RR（p = 0.982）和NRM（p = 0.320）的独立风险因素。我们的研究受限于缺乏依据ELN 2022指南的更全面的分子数据，采用ELN 2010风险分层。我们得出结论：在t-AML的治疗方案中，尤其是在关于异基因造血干细胞移植（allo-HSCT）方面，应以ELN遗传风险为指导，而非仅依据t-AML分类。我们的数据支持WHO和ICC 2022的分类标准，将t-AML作为诊断限定词而非单独亚类。

Abstract

Therapy-related acute myeloid leukemia (t-AML) often exhibits adverse (genetic) features. There is ongoing discussion on the impact of t-AML on long-term outcome in AML. Therefore, we retrospectively analyzed clinical and biological characteristics of 1133 AML patients (225 t-AML patients and 908 de novo AML patients) with a median follow-up of 81.8 months. T-AML patients showed more adverse genetic alterations, higher age and more comorbidities as compared to de novo AML. Median OS in intensively treated t-AML patients was 13.7 months as compared to 39.4 months in de novo AML (p < 0.001). With non-intensive therapy, OS did not differ significantly (p = 0.394). With intensive therapy, significant differences in favor of de novo AML were observed in the ELN intermediate I/II (p = 0.009) and adverse (p = 0.016) risk groups but not within favorable risk groups (APL p = 0.927, ELN favorable p = 0.714). However, t-AML was no independent risk factor for OS (p = 0.103), RR (p = 0.982) and NRM (p = 0.320) in the multivariate analysis. A limitation of our study is an ELN 2010 risk stratification due to a lack of more comprehensive molecular data according to ELN 2022. We conclude that therapeutic algorithms in t-AML, in particular with regard to allo-HSCT, should be guided by ELN genetic risk rather than classification as t-AML alone. Our data support the WHO and ICC 2022 classifications, which include t-AML as diagnostic qualifier rather than a separate subcategory.