TP53畸变构成骨髓增生异常肿瘤(MDS)和急性髓细胞性白血病(AML)的最高风险子集。国际共识分类质疑MDS和AML之间的爆炸阈值。在这项研究中,我们评估了76例TP53异常患者的MDS和AML之间的区别.我们在TP53基因组学方面观察到MDS和AML之间没有显着差异。整个组的中位总生存期(OS)为223天,但是亚组中的预后区分显示,对于多重等位基因状态加上TP53变异等位基因频率(VAF)>50%的AML,OS(46天)最差。在多变量分析中,未调整的Cox模型显示以下变量是死亡率的独立危险因素:AML(vs.MDS)(风险比[HR]:2.50,置信区间[CI]:1.4-4.4,p=0.001),复杂核型(HR:3.00,CI:1.4-6.1,p=0.003),多重状态(HR:2.30,CI1.3-4.2,p=0.005),和没有造血细胞移植(HCT)(HR:3.90,CI:1.8-8.9,p=0.0009)。克隆动态建模显示,使用一线低甲基化剂的TP53VAF显着降低。这些发现阐明了特异性协变量对TP53异常髓系肿瘤预后的影响,无论MDS还是AML的诊断,并可能影响HCT决策。
TP53 aberrations constitute the highest risk subset of myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). The International Consensus Classification questions the blast threshold between MDS and AML. In this study, we assess the distinction between MDS and AML for 76 patients with TP53 aberrations. We observed no significant differences between MDS and AML regarding TP53 genomics. Median overall survival (OS) was 223 days for the entire group, but prognostic discrimination within subgroups showed the most inferior OS (46 days) for AML with multihit allelic state plus TP53 variant allele frequency (VAF) > 50%. In multivariate analysis, unadjusted Cox models revealed the following variables as independent risk factors for mortality: AML (vs. MDS) (hazard ratio [HR]: 2.50, confidence interval [CI]: 1.4-4.4, p = 0.001), complex karyotype (HR: 3.00, CI: 1.4-6.1, p = 0.003), multihit status (HR: 2.30, CI 1.3-4.2, p = 0.005), and absence of hematopoietic cell transplant (HCT) (HR: 3.90, CI: 1.8-8.9, p = 0.0009). Clonal dynamic modeling showed a significant reduction in TP53 VAF with front-line hypomethylating agents. These findings clarify the impact of specific covariates on outcomes of TP53-aberrant myeloid neoplasms, irrespective of the diagnosis of MDS versus AML, and may influence HCT decisions.