Impact of Chemotherapy Delay on Overall Survival for AML with <i>IDH1/2</i> Mutations: A Study in Adult Chinese Patients

The effect of time from diagnosis to treatment (TDT) on overall survival of patients with acute myeloid leukemia (AML) remains obscure. Furthermore, whether chemotherapy delay impacts overall survival (OS) of patients with a special molecular subtype has not been investigated. Here, we enrolled 364 cases of AML to assess the effect of TDT on OS by fractional polynomial regression in the context of clinical parameters and genes of FLT3ITD, NPM1, CEBPA, DNMT3a, and IDH1/2 mutations. Results of the current study show IDH1/2 mutations are associated with older age, M0 morphology, an intermediate cytogenetic risk group, and NPM1 mutations. TDT associates with OS for AML patients in a nonlinear pattern with a J shape. Moreover, adverse effect of delayed treatment on OS was observed in patients with IDH1/2 mutations, but not in those with IDH1/2 wildtype. Therefore, initiating chemotherapy as soon as possible after diagnosis might be a potential strategy to improve OS in AML patients with IDH1/2 mutations.急性髓系白血病（Acute Myeloid Leukemia, AML）患者的确诊至治疗间隔时间（Time From Diagnosis to Treatment, TDT）对总生存期的影响仍未明确。此外，化疗延迟是否会对特定分子亚型AML患者的总生存期（Overall Survival, OS）产生影响，目前尚无相关研究。本研究纳入364例AML患者，结合临床参数及FLT3ITD、NPM1、CEBPA、DNMT3a、IDH1/2突变基因状态，采用分数多项式回归分析TDT对OS的影响。本研究结果显示，IDH1/2突变与高龄、M0形态学表型、中等细胞遗传学危险度分组及NPM1突变呈显著相关。AML患者的TDT与OS呈非线性相关，且呈现J型曲线特征。此外，治疗延迟对OS的不良影响仅见于IDH1/2突变患者，在IDH1/2野生型患者中未观察到此效应。因此，对于携带IDH1/2突变的AML患者，确诊后尽早启动化疗或为改善其总生存期的潜在临床策略。