Ghimire Bipin, Zimmer Markie, Donthireddy Vijayalakshmi
Department of Hematology and Oncology, Henry Ford Health, Detroit, Michigan, USA.
Eur J Haematol. 2025 Jun;114(6):924-937. doi: 10.1111/ejh.14404. Epub 2025 Mar 4.
Patients with acute myeloid leukemia (AML) harboring mutations in TP53 (TP53-MT) have poor responses to current therapies and unfavorable prognoses. Despite the recognition of variant TP53 as an adverse feature of AML, an optimal treatment regimen has not yet been established, underlining a critical need for new, more effective therapeutic combinations and novel treatments. We present the case of a patient with TP53-MT AML and marked myelodysplasia who developed primary refractory disease after induction therapy with the intensive chemotherapy regimen of liposomal daunorubicin and cytarabine. Our patient's optimal response to second induction chemotherapy with FLAG-Ida prompted an exploration of established and investigational treatment regimens for this specific high-risk AML subtype. Therefore, we performed a comprehensive literature review of findings from studies exploring AML therapies, focusing on outcomes for patients with TP53-MT AML. The summary provided here reveals the complexity of defining the therapeutic responses of patients with the heterogeneous TP53-MT genetic background and the challenges in treating this high-risk form of AML. Future work must continue to investigate novel therapies and combinations to improve patient outcomes in this vulnerable population.
携带TP53突变(TP53-MT)的急性髓系白血病(AML)患者对当前治疗反应不佳,预后不良。尽管已认识到变异型TP53是AML的不良特征,但尚未确立最佳治疗方案,这突出表明迫切需要新的、更有效的治疗组合和新的治疗方法。我们报告了1例TP53-MT AML且有明显骨髓发育异常的患者,该患者在接受脂质体柔红霉素和阿糖胞苷强化化疗方案诱导治疗后出现原发性难治性疾病。我们的患者对FLAG-Ida第二次诱导化疗的最佳反应促使我们探索针对这种特定高危AML亚型的既定和研究性治疗方案。因此,我们对探索AML治疗的研究结果进行了全面的文献综述,重点关注TP53-MT AML患者的治疗结果。此处提供的总结揭示了定义具有异质性TP53-MT基因背景患者治疗反应的复杂性以及治疗这种高危AML形式所面临的挑战。未来的工作必须继续研究新的治疗方法和组合,以改善这一脆弱人群的患者治疗结果。