Abstract：
Molecular measurable residual disease (MRD, eg, by real-time quantitative polymerase chain reaction, RT-qPCR), is an integral part of response assessment in acute myeloid leukemia (AML) with established prognostic and evolving therapeutic significance. MRD failure can occur through several pathways (namely MRD persistence at the end of treatment at a high level, MRD progression from a low level or MRD re-emergence during follow up; the latter two constitute MRD relapse as defined by the European Leukemia Net) and is clinically actionable, with survival benefit reported in AML subgroups. Selection of pre-emptive therapy at MRD failure relies upon an integrated clinico-molecular assessment and is subset-specific. In acute promyelocytic leukemia, arsenic trioxide-based regimen for MRD failure following frontline treatment with all-trans-retinoic acid plus chemotherapy represents standard of care, while hypomethylating agents (eg, azacitidine), salvage chemotherapy (eg, FLAG-IDA) and venetoclax-based regimens are effective in NPM1-mutated AML. Specific inhibitors of FLT3 have emerging use in FLT3-mutated AML and are associated with minimal toxicity. Furthermore, immunotherapeutic approaches such as donor lymphocyte infusions and interferon-⍺ are efficacious options in the post-allogeneic-HSCT settings. Enrollment into clinical trials with genomic-guided assignment of pre-emptive therapy at MRD failure should be prioritized. Finally, with the emergence of novel agents (eg, menin inhibitors) and approaches (eg, adoptive cellular and immunological therapy), an exciting future lies ahead where a broad array of highly active pre-emptive therapeutic options will likely be clinically applicable to a wide range of AML subsets.
摘要：
分子可测量残留病（MRD，例如，通过实时定量聚合酶链反应，RT-qPCR），是急性髓细胞性白血病（AML）反应评估的重要组成部分，具有确定的预后和不断发展的治疗意义。MRD失败可以通过几种途径发生（即在高水平治疗结束时MRD持续存在，MRD从低水平进展或随访期间MRD复发；后两者构成欧洲白血病网定义的MRD复发），具有临床可行性，在AML亚组中报告了生存获益。MRD失败时抢先治疗的选择依赖于综合的临床分子评估，并且是子集特异性的。在急性早幼粒细胞白血病中，以三氧化二砷为基础的全反式维甲酸加化疗一线治疗后MRD失败的方案代表了护理标准，而低甲基化剂(如，阿扎胞苷)，挽救性化疗(如，FLAG-IDA）和基于venetoclax的方案在NPM1突变的AML中有效。FLT3的特异性抑制剂在FLT3突变的AML中已经出现用途并且与最小的毒性相关。此外，在同种异体后的HSCT设置中,供体淋巴细胞输注和干扰素等免疫治疗方法是有效的选择.应优先考虑在MRD失败时进行基因组指导的先发制人治疗的临床试验。最后,随着新型药剂的出现(例如，menin抑制剂)和方法(例如，过继细胞和免疫疗法)，一个令人兴奋的未来即将到来,一系列高度活跃的先发制人治疗方案可能在临床上适用于广泛的AML亚群.
