H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Maur y Regional Cancer Center, Columbia, TN.
Haematologica. 2020 Jan 31;105(2):398-406. doi: 10.3324/haematol.2018.208637. Print 2020.
In older patients with acute myeloid leukemia, the more frequent presence of biologically inherent therapy-resistant disease and increased comorbidities translate to poor overall survival and therapeutic challenges. Optimal front-line therapies for older patients with acute myeloid leukemia remain controversial. We retrospectively evaluated survival outcomes in 980 elderly (≥70 years) acute myeloid leukemia patients from a single institution between 1995 and 2016. Four treatment categories were compared: high-intensity (daunorubicin/cytarabine or equivalent), hypomethylating agent, low-intensity (low-dose cytarabine or similar without hypomethylating agents), and supportive care therapy (including hydroxyurea). At a median follow up of 20.5 months, the median overall survival for the entire cohort was 7.1 months. Multivariate analysis identified secondary acute myeloid leukemia, poor-risk cytogenetics, performance status, front-line therapy, age, white blood cell count, platelet count, and hemoglobin level at diagnosis as having an impact on survival. High-intensity therapy was used in 360 patients (36.7%), hypomethylating agent in 255 (26.0%), low-intensity therapy in 91 (9.3%), and supportive care in 274 (28.0%). Pairwise comparisons between hypomethylating agent therapy and the three other treatment groups demonstrated statistically significant superior median overall survival with hypomethylating agent [14.4 months) high-intensity therapy 10.8 months, hazard ratio 1.35, 95% confidence interval (CI): 1.10-1.65; =0.004], low-intensity therapy (5.9 months, hazard ratio 2.01, 95%CI: 1.53-2.62; <0.0001), and supportive care (2.1 months, hazard ratio 2.94, 95%CI: 2.39-3.61; <0.0001). Our results indicate a significant survival benefit with hypomethylating agents compared to high-intensity, low-intensity, or supportive care. Additionally, high-intensity chemotherapy resulted in superior overall outcomes compared to low-intensity therapy and supportive care. Results from this study highlight the need for novel therapeutic approaches besides utilization of intensive chemotherapy in this specific aged population.
在老年急性髓系白血病患者中,更频繁地存在生物学上固有的治疗耐药疾病和增加的合并症,导致总体生存率差和治疗挑战。对于老年急性髓系白血病患者的最佳一线治疗仍存在争议。我们回顾性评估了 1995 年至 2016 年间单中心 980 例(≥70 岁)老年急性髓系白血病患者的生存结局。比较了四种治疗类别:高强度(柔红霉素/阿糖胞苷或等效物)、低甲基化剂、低强度(低剂量阿糖胞苷或类似物而无低甲基化剂)和支持性护理治疗(包括羟基脲)。在中位随访 20.5 个月时,整个队列的中位总生存期为 7.1 个月。多变量分析确定继发性急性髓系白血病、不良风险细胞遗传学、表现状态、一线治疗、年龄、白细胞计数、血小板计数和血红蛋白水平在诊断时对生存有影响。高强度治疗在 360 例患者(36.7%)、低甲基化剂治疗在 255 例患者(26.0%)、低强度治疗在 91 例患者(9.3%)和支持性护理治疗在 274 例患者(28.0%)中使用。低甲基化剂治疗与其他三组治疗的两两比较显示,低甲基化剂治疗的中位总生存期明显优于其他三组[14.4 个月,高强度治疗为 10.8 个月,风险比 1.35,95%置信区间(CI):1.10-1.65;=0.004]、低强度治疗(5.9 个月,风险比 2.01,95%CI:1.53-2.62;<0.0001)和支持性护理(2.1 个月,风险比 2.94,95%CI:2.39-3.61;<0.0001)。我们的结果表明,与高强度、低强度或支持性护理相比,低甲基化剂治疗具有显著的生存获益。此外,高强度化疗与低强度治疗和支持性护理相比,总体结局更优。这项研究的结果强调,除了在这一特定老年人群中使用强化化疗外,还需要新的治疗方法。