Vachhani Pankit, Al Yacoub Raed, Miller Austin, Zhang Fan, Cronin Tara L, Ontiveros Evelena P, Thompson James E, Griffiths Elizabeth A, Wang Eunice S
Department of Medicine, Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets, Buffalo, NY, USA.
Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA.
Leuk Res. 2018 Dec;75:29-35. doi: 10.1016/j.leukres.2018.10.011. Epub 2018 Oct 25.
Acute myeloid leukemia (AML) in older patients is often associated with biologic and clinical characteristics that predict poor outcomes to cytarabine and anthracycline based induction chemotherapy (IC). The impact of hypomethylating agents (HMA) in the treatment of these high-risk patients is unknown. Here we retrospectively examined the remission rates and survival outcomes of 201 newly diagnosed patients ≥60 years old with therapy-related (t-AML), secondary (s-AML), or AML with myelodysplasia-related changes (AML-MRC). Ninety-eight patients received IC, and 103 received HMA. Patients in the IC cohort were younger than those who received HMA (68 vs. 74 years; p < 0.01) with lower comorbidity burden. Composite complete remission rates (CR) were 39% in IC and 27% in the HMA cohorts (p = 0.10). Overall survival (OS) was not significantly different between the two cohorts (7.59 mos vs. 5.49 mos; HR 0.75 95% CI 0.55-1.02) despite the fact that more patients in the IC cohort (33% versus 5%, p < 0.01) underwent allogeneic stem cell transplant. Patients with t-AML (HR 0.56; 95% CI 0.33-0.97) and complex karyotype without monosomal karyotype (CK + MK-; HR 0.37; 95% CI 0.19-0.75) had better OS following IC. Patients with CK + MK+ (HR 2.00; 95% CI 1.08-3.70) had improved OS following HMA. Our results support the use of HMA as an alternative upfront regimen in older individuals with newly diagnosed high-risk AML based on similar clinical outcomes to IC.
老年患者的急性髓系白血病（AML）通常与一些生物学和临床特征相关，这些特征预示着基于阿糖胞苷和蒽环类药物的诱导化疗（IC）效果不佳。低甲基化药物（HMA）在这些高危患者治疗中的作用尚不清楚。在此，我们回顾性研究了201例年龄≥60岁的新诊断的治疗相关性（t-AML）、继发性（s-AML）或伴有骨髓增生异常相关改变的AML（AML-MRC）患者的缓解率和生存结果。98例患者接受了IC治疗，103例接受了HMA治疗。IC队列中的患者比接受HMA治疗的患者年轻（68岁对74岁；p<0.01），合并症负担更低。IC队列的综合完全缓解率（CR）为39%，HMA队列中为27%（p=0.10）。尽管IC队列中有更多患者（33%对5%，p<0.01）接受了异基因干细胞移植，但两个队列的总生存期（OS）并无显著差异（7.59个月对5.49个月；HR 0.75，95%CI 0.55-1.02）。t-AML患者（HR 0.56；95%CI 0.33-0.97）和无单倍体核型的复杂核型患者（CK+MK-；HR 0.37；95%CI 0.19-0.75）在接受IC治疗后OS较好。CK+MK+患者（HR 2.00；95%CI 1.08-3.70）在接受HMA治疗后OS有所改善。我们的结果支持将HMA作为新诊断的高危AML老年患者的替代一线治疗方案，因为其临床结果与IC相似。
