Clinical Results of Hypomethylating Agents in AML Treatment.
Clinical Results of Hypomethylating Agents in AML Treatment.
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DOI：
10.3390/jcm4010001
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发表时间：
2014-12-25
影响因子：
3.9
通讯作者：
Huls G
中科院分区：
文献类型：
--
作者：
Cruijsen M;Lübbert M;Wijermans P;Huls G
表观遗传学改变在急性髓细胞白血病（AML）的发生发展中起重要作用。与基因突变不同，表观遗传变化是潜在可逆的，这使得它们对治疗干预具有吸引力。影响表观遗传学的药物是DNA甲基转移酶抑制剂、阿扎胞苷和地西他滨。由于其相对轻微的副作用，阿扎胞苷和地西他滨特别适用于治疗老年患者和合并症患者。这两种药物对具有不利细胞遗传学特征的AML母细胞具有显著活性。最近的3期临床试验表明，阿扎胞苷和地西他滨与传统治疗相比，对老年AML患者（不适合强化治疗）具有优越性。已报告了标准阿扎胞苷（7天75 mg/m2 SC;每4周一次）和地西他滨（5天20 mg/m2 IV;每4周一次）方案改良的治疗结果。特别地，10天地西他滨方案的结果是有希望的，揭示了约45%的完全缓解（CR）率（CR + CRi（即，血细胞计数恢复不完全的CR约为64%，几乎与强化化疗相当。应用低甲基化剂以最小的毒性为代价控制AML是一种非常有前途的策略，可以将患有合并症的老年患者与异基因造血细胞移植的潜在治愈性治疗“桥接”。在这篇文章中，我们讨论了DNA甲基转移酶抑制剂在AML中的作用。
Epigenetic changes play an important role in the development of acute myeloid leukemia (AML). Unlike gene mutations, epigenetic changes are potentially reversible, which makes them attractive for therapeutic intervention. Agents that affect epigenetics are the DNA methyltransferase inhibitors, azacitidine and decitabine. Because of their relatively mild side effects, azacitidine and decitabine are particularly feasible for the treatment of older patients and patients with co-morbidities. Both drugs have remarkable activity against AML blasts with unfavorable cytogenetic characteristics. Recent phase 3 trials have shown the superiority of azacitidine and decitabine compared with conventional care for older AML patients (not eligible for intensive treatment). Results of treatment with modifications of the standard azacitidine (seven days 75 mg/m2 SC; every four weeks) and decitabine (five days 20 mg/m2 IV; every four weeks) schedules have been reported. Particularly, the results of the 10-day decitabine schedule are promising, revealing complete remission (CR) rates around 45% (CR + CRi (i.e., CR with incomplete blood count recovery) around 64%) almost comparable with intensive chemotherapy. Application of hypomethylating agents to control AML at the cost of minimal toxicity is a very promising strategy to “bridge” older patients with co-morbidities to the potential curative treatment of allogeneic hematopoietic cell transplantation. In this article, we discuss the role of DNA methyltransferase inhibitors in AML.
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