药物基因组评分有效地个性化了急性髓性白血病的治疗
Richard J Marrero1, Huiyun Wu2, Xueyuan Cao3
1Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida.
概括
使用10-SNP ara-C (ACS10) 评分,为急性髓性白血病 (AML) 量身定制化疗改善了患者的治疗结果. 预防性基因型鉴定可以帮助将患者与AML治疗最有效的诱导疗法相匹配.
科学领域:
- 药物基因组学 药物基因组学
- 儿科瘤学 儿科瘤学
- 血液学恶性瘤是什么
背景情况:
- 赛塔拉宾 (ara-C) 是急性髓性白血病 (AML) 化疗的基石.
- 之前的研究发现,与治疗结果相关的10-SNP ara-C (ACS10) 评分.
- 低ACS10分数 (≤0) 表明AML患者的标准化疗结果不佳.
研究的目的:
- 评估儿童AML患者的ACS10评分的预测值.
- 根据ACS10分数分层,评估三种不同的诱导方案的疗效.
- 确定个性化诱导方案是否可以改善无事件生存 (EFS) 和整体生存 (OS).
主要方法:
- 从AML02和AML08临床试验中对儿科AML患者的回顾性分析.
- 将患者分为低 (≤0) 和高 (>0) ACS10分数组的分层.
- 在三个诱导疗法中,EFS和OS的比较:低剂量阿拉C (LDAC),高剂量阿拉C (HDAC) 和克洛法拉宾+阿拉C (Clo/ara-C).
主要成果:
- 在低ACS10组中,与LDAC相比,Clo/ara-C显著改善了EFS和OS (EFS HR=0.45,OS HR=0.44).
- 在高ACS10组中,Clo/ara-C对EFS或OS没有显著的好处,而不是LDAC.
- 基于ACS10分数的个性化诱导方案预测,与非个性化方法相比,结果有9%的改善 (P < 0.002).
结论:
- 使用ACS10评分量身定制的诱导方案可以显著提高儿科AML患者的结果.
- 细菌单核酸多态性 (SNP) 基因定型允许预防性匹配有效的AML诱导疗法.
- 个性化化疗策略有望提高AML治疗疗效.
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