Sumransub Nuttavut, Steinwand Gabriel K, Cordner Keith, Lee Yoonkyu, Cao Qing, Allred Jeremy, Bachanova Veronika, Juckett Mark, Eckfeldt Craig, Maakaron Joseph E, Tracy Sean I, Ramesh Vidhyalakshmi, Nelson Andrew C, Yohe Sophia, Sachs Zohar
Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
M Health Fairview, Department of Pharmacy, University of Minnesota Medical Center, Minneapolis, MN 55455, USA.
Cancers (Basel). 2024 Aug 7;16(16):2784. doi: 10.3390/cancers16162784.
mutations (m) define the most treatment-refractory acute myeloid leukemia (AML) subtype. Optimal treatment approaches have not been established in this setting. We reviewed our institutional experience to identify therapy sequencing, treatment response, and survival patterns in these patients.
This study was a single-center, retrospective cohort analysis.
Our cohort includes 86 m and 337 wild-type (wt) adult AML patients. m AML patients presented with lower bone marrow and peripheral blasts; none presented with hyperleukocytosis. Patients who received intensive treatment up front demonstrated superior overall survival (OS) over those receiving first-line non-intensive therapy (2-year OS 22% versus 7%; = 0.02). However, the complete remission (CR) rates among the first-line intensive and non-intensive therapy groups were comparable (21.9% and 29.4%, respectively, = 0.49). The improved OS is therefore attributed to superior cumulative CR in the intensive group. First-line intensively treated patients were more likely to receive and respond to salvage, leading to a cumulative CR rate of 65.7% (versus 29.4%, = 0.003). Achieving CR at any point is strongly associated with superior survival outcomes with 2-year OS of 31% versus 0% for those not achieving CR ever ( < 0.01).
We find that m AML rarely presents with oncological emergencies, suggesting that clinical trial enrollment is feasible in this group. Additionally, in our cohort, intensive induction therapies lead to superior survival outcomes attributed to successful salvage therapy. These data suggest that strategic therapy sequencing and salvage therapy may be important in optimizing outcomes for m AML patients.
突变（m）定义了最难治疗的急性髓系白血病（AML）亚型。在这种情况下尚未确立最佳治疗方法。我们回顾了我们机构的经验，以确定这些患者的治疗顺序、治疗反应和生存模式。
本研究为单中心回顾性队列分析。
我们的队列包括86例m型和337例野生型（wt）成年AML患者。m型AML患者的骨髓和外周血原始细胞较低；无一例出现白细胞增多症。 upfront接受强化治疗的患者总生存期（OS）优于接受一线非强化治疗的患者（2年OS分别为22%和7%；P = 0.02）。然而，一线强化治疗组和非强化治疗组的完全缓解（CR）率相当（分别为21.9%和29.4%，P = 0.49）。因此，OS的改善归因于强化组更高的累积CR率。一线接受强化治疗的患者更有可能接受挽救治疗并产生反应，导致累积CR率为65.7%（相比之下为29.4%，P = 0.003）。在任何时间点实现CR都与更好的生存结果密切相关，实现CR的患者2年OS为31%，而从未实现CR的患者为0%（P < 0.01）。
我们发现m型AML很少出现肿瘤急症，这表明该组患者进行临床试验入组是可行的。此外，在我们的队列中，强化诱导治疗可带来更好的生存结果，这归因于成功的挽救治疗。这些数据表明，策略性的治疗顺序和挽救治疗对于优化m型AML患者的结局可能很重要。
