Efficacy of the hypomethylating agents as frontline, salvage, or consolidation therapy in adults with acute myeloid leukemia (AML).
Efficacy of the hypomethylating agents as frontline, salvage, or consolidation therapy in adults with acute myeloid leukemia (AML).
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DOI：
10.1007/s00277-013-1940-9
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发表时间：
2014-01
影响因子：
3.5
通讯作者：
Pardee, Timothy
中科院分区：
文献类型：
--
作者：
Tawfik, Bernard;Sliesoraitis, Sarunas;Lyerly, Susan;Klepin, Heidi D.;Lawrence, Julia;Isom, Scott;Ellis, Leslie R.;Manuel, Megan;Dralle, Sarah;Berenzon, Dmitriy;Powell, Bayard L.;Pardee, Timothy
低甲基化药物（HA）阿扎胞苷和地西他滨已成为AML患者初始和挽救治疗的替代药物。关于AML在标准治疗后对低甲基化剂的反应知之甚少，这些药物在真实的世界环境中的活性也没有得到很好的研究。我们回顾性分析了2002-2011年在维克森林接受HA一线治疗（n=34）、挽救治疗（n=28）或巩固治疗（n=13）的75例连续AML患者的数据。我们收集了有关年龄、性别、种族、Charlson Comorrhage指数（CCI）、细胞遗传学、治疗类型、完全缓解（CR）、完全缓解伴不完全计数恢复（CRi）和生存率的数据。使用Kaplan-Meier估计值和考克斯比例风险模型进行统计分析。一线缓解率（CR+CRi）为26.5%，中位总生存期（OS）为3.4（95%CI 1.3-7.4）个月，1年时存活率为18%。在挽救队列中，缓解率显著低于一线治疗（3.6% vs 26.5%，p=0.017）。尽管缓解率降低，但HA治疗后的OS长于一线治疗，为8.2（CI 4.8-10.3）个月。在巩固队列中，OS为13.8（CI 8.0 - 21.6）个月，1例患者在诊断后超过30个月时缓解。这些数据表明，既往细胞毒性治疗降低了HA的骨髓应答率，但未降低生存率。此外，使用低甲基化药物巩固治疗导致老年患者队列的中位总生存期超过1年。这表明低甲基化剂在AML治疗的所有阶段都具有活性。
The hypomethylating agents (HA), azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with AML. Little is known about how AML responds to hypomethylating agents after standard therapy and the activity of these agents in a real world setting is not well studied. We retrospectively examined data for 75 consecutive AML patients at Wake Forest from 2002–2011 treated with HAs either as 1st line (n=34), salvage (n=28) or consolidation (n=13). We collected data on age, gender, race, Charlson Comorbidity index (CCI), cytogenetics, type of treatment, Complete Remission (CR), Complete Remission with incomplete count recovery (CRi), and survival. Statistical analysis was performed using Kaplan-Meier estimates and cox proportional hazards models. Frontline response rate (CR+CRi) was 26.5%, median overall survival (OS) was 3.4 (95% CI 1.3–7.4) months, with 18% alive at one year. In the salvage cohort, the response rate was significantly lower compared to frontline (3.6% versus 26.5%, p=0.017). Despite the reduced response, OS from time of HA treatment was longer than frontline at 8.2 (CI 4.8–10.3) months. In the consolidation cohort OS was 13.8 (CI 8.0 – 21.6) months with one patient in remission more than 30 months from diagnosis. These data suggest prior cytotoxic therapy decrease marrow response rates to HAs but not survival. Furthermore, use of hypomethylating agents for consolidation resulted in a median overall survival over one year in a cohort of older patients. This suggests that hypomethylating agents have activity in all phases of AML treatment.
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影响因子：
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作者：
Burnett, Alan K.;Milligan, Donald;Wheatley, Keith
通讯作者：
Wheatley, Keith
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