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.

中文翻译：

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接受治疗的继发性急性髓性白血病患者的结局：一种需要独立预后指定的高危亚型


在接受骨髓增生异常综合征 （MDS） 或相关疾病治疗后发展为急性髓系白血病 （AML） 的患者预后特别差。本研究分析了既往患有 MDS、慢性粒单核细胞白血病 （CMML） 或 MDS/骨髓增生性肿瘤 （MPN） 重叠综合征，并接受过低甲基化药物、化疗和/或同种异体干细胞移植 （HSCT） 的新诊断 AML 成年患者这些先行疾病。从 2012 年 1 月到 2023 年 8 月，我们纳入了 673 名中位年龄为 70 岁 （范围为 19-94） 的患者;536 例 （80%） 从 MDS 转化而来，其余从 CMML 或 MDS-MPN 转化而来。此外，149 例患者 （22%） 既往接受过非髓系恶性肿瘤治疗。在 497 名可评估的患者中，289 名 （58%） 具有不良风险 （AR） 细胞遗传学，34% 具有 TP53 突变/s，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% 接受了维奈托克治疗。总缓解率为 37%，维奈托克提高了 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）、≥ 2 线治疗先前的髓系疾病 （HR = 1.23） 和 ELN AR 风险 （HR = 1.47） 增加了死亡风险，而 HSCT （HR = 0.50） 是有益的，并在梯度增强回归上得到了验证。无论 AML 基因组学和治疗如何，TS-AML 都与不良结果相关，这凸显了将其作为独立 AR 类别进行准确预测和临床试验报告的必要性。