Norsworthy Kelly J, DeZern Amy E, Tsai Hua-Ling, Hand Wesley A, Varadhan Ravi, Gore Steven D, Gojo Ivana, Pratz Keith, Carraway Hetty E, Showel Margaret, McDevitt Michael A, Gladstone Douglas, Ghiaur Gabriel, Prince Gabrielle, Seung Amy H, Benani Dina, Levis Mark J, Karp Judith E, Smith B Douglas
Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States.
Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States; Yale Cancer Center, New Haven, CT, United States.
Leuk Res. 2017 Oct;61:25-32. doi: 10.1016/j.leukres.2017.08.009. Epub 2017 Aug 30.
Timed sequential therapy (TST) aims to improve outcomes in acute myelogenous leukemia (AML) by harnessing drug-induced cell cycle kinetics of AML, where a second drug is timed to coincide with peak leukemia proliferation induced by the first drugs. We analyzed outcomes in 301 newly diagnosed AML patients treated from 2004-2013 with cytarabine, anthracycline, and etoposide TST induction. Median age was 52 (range 20-74) and complete remission rate 68%. With median follow-up 5.8 years, 5-year DFS and overall survival (OS) were 37% (95% CI 31-45%) and 32% (95% CI 27-38%), respectively. In multivariate analysis, older age, unfavorable cytogenetics, and WBC≥50×10/L resulted in worse OS. Among patients not undergoing blood and marrow transplant, a propensity score analysis, which reduces imbalance in baseline characteristics, showed consolidation with TST compared with 1 or more cycles high-dose cytarabine trended toward lower DFS and post-remission survival with hazard ratio (HR) 1.9 (95% CI 0.9-4.0), and 1.6 (95% CI 0.7-3.6), respectively. Our results demonstrate the efficacy and feasibility of TST induction for newly diagnosed patients with AML, with results comparable to that seen in clinical trials with other TST therapies and 7+3.
定时序贯疗法（TST）旨在通过利用急性髓系白血病（AML）药物诱导的细胞周期动力学来改善AML的治疗结果，即第二种药物的给药时间与第一种药物诱导的白血病细胞增殖高峰期相吻合。我们分析了2004年至2013年接受阿糖胞苷、蒽环类药物和依托泊苷TST诱导治疗的301例新诊断AML患者的治疗结果。中位年龄为52岁（范围20 - 74岁），完全缓解率为68%。中位随访5.8年，5年无病生存率（DFS）和总生存率（OS）分别为37%（95%置信区间31 - 45%）和32%（95%置信区间27 - 38%）。多因素分析显示，年龄较大、细胞遗传学不良以及白细胞计数≥50×10⁹/L会导致较差的总生存率。在未接受血液和骨髓移植的患者中，倾向评分分析减少了基线特征的不平衡，结果显示与1个或更多周期的大剂量阿糖胞苷巩固治疗相比，TST巩固治疗的DFS和缓解后生存率呈下降趋势，风险比（HR）分别为1.9（95%置信区间0.9 - 4.0）和1.6（95%置信区间0.7 - 3.6）。我们的结果证明了TST诱导治疗新诊断AML患者的有效性和可行性，其结果与其他TST疗法及7 + 3方案的临床试验结果相当。
