Senapati Jayastu, Kantarjian Hagop M, Haddad Fadi G, Short Nicholas J, Borthakur Gautam, Kanagal-Shamanna Rashmi, Tang Guilin, Jabbour Elias, DiNardo Courtney D, Daver Naval, Montalban-Bravo Guillermo, Shah Vishrut, Alousi Amin, Shpall Elizabeth, Popat Uday, Garcia-Manero Guillermo, Ravandi Farhad, Kadia Tapan M
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Am J Hematol. 2025 Feb;100(2):249-259. doi: 10.1002/ajh.27561. Epub 2024 Dec 24.
Patients who develop acute myeloid leukemia (AML) after having received treatment for myelodysplastic syndrome (MDS) or related conditions have particularly poor outcomes. This study analyzed adult patients with newly diagnosed AML who previously had MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome, and who had received hypomethylating agents, chemotherapy, and/or allogeneic stem cell transplantation (HSCT) for these antecedent disorders. From January 2012 to August 2023, we included 673 patients with a median age of 70 years (range, 19-94); 536 (80%) had transformed from MDS, and the remainder from CMML or MDS-MPN. Additionally, 149 patients (22%) had prior therapy for nonmyeloid malignancies. Among 497 evaluable patients, 289 (58%) had adverse-risk (AR) cytogenetics, 34% had TP53 mutation/s, and 71% were classified as AR by the ELN 2017 criteria. Most patients (67%) received low-intensity therapy (LIT) for AML, and 27% were treated with venetoclax. The overall response rate was 37%, and venetoclax improved the odds of response (OR = 2.5, 95% CI 1.6-3.7) in LIT-treated patients. At a median follow-up of 43 months, the median relapse-free survival (RFS) and overall survival (OS) were 4.6 and 4.8 months, respectively. Multivariate analysis showed that prior therapy for nonmyeloid disorders (HR = 1.30), ≥ 2 lines of therapy for antecedent myeloid disorders (HR = 1.23), and ELN AR risk (HR = 1.47) increased the hazards of death, while HSCT (HR = 0.50) was beneficial and validated on gradient-boosted regression. TS-AML is associated with poor outcomes irrespective of AML genomics and treatment, highlighting the need for its inclusion as an independent AR category for accurate prognostication and clinical trial reporting.
在接受骨髓增生异常综合征（MDS）或相关病症治疗后发生急性髓系白血病（AML）的患者预后特别差。本研究分析了新诊断为AML的成年患者，这些患者既往患有MDS、慢性粒单核细胞白血病（CMML）或MDS/骨髓增殖性肿瘤（MPN）重叠综合征，并且曾因这些前驱疾病接受过去甲基化药物、化疗和/或异基因干细胞移植（HSCT）。从2012年1月至2023年8月，我们纳入了673例患者，中位年龄为70岁（范围19 - 94岁）；536例（80%）由MDS转化而来，其余由CMML或MDS - MPN转化而来。此外，149例患者（22%）曾接受过非髓系恶性肿瘤的治疗。在497例可评估患者中，289例（58%）具有不良风险（AR）细胞遗传学特征，34%有TP53突变，71%根据ELN 2017标准被归类为AR。大多数患者（67%）接受了AML的低强度治疗（LIT），27%接受了维奈克拉治疗。总体缓解率为37%，维奈克拉提高了LIT治疗患者的缓解几率（OR = 2.5，95% CI 1.6 - 3.7）。中位随访43个月时，中位无复发生存期（RFS）和总生存期（OS）分别为4.6个月和4.8个月。多变量分析显示，非髓系疾病的既往治疗（HR = 1.30）、前驱髓系疾病≥2线治疗（HR = 1.23）以及ELN AR风险（HR = 1.47）增加了死亡风险，而异基因干细胞移植（HSCT）（HR = 0.50）有益且在梯度提升回归分析中得到验证。无论AML的基因组学和治疗情况如何，治疗相关的AML（TS - AML）都与不良预后相关，这凸显了将其作为一个独立的AR类别纳入以进行准确预后评估和临床试验报告的必要性。
