Post-remission therapy in acute myeloid leukemia (AML) remains problematic. It has been demonstrated that younger patients can maintain longer complete remissions (CR) with aggressive post-remission therapies after induction treatment: allogeneic (allo), autologous (auto) stem cell transplantation (SCT), or intensive chemotherapy (ICC). The purpose of our study was to identify the most important randomized and controlled studies comparing these three therapeutic options, in order to draw conclusions and possible suggestions for post-remission therapy of AML, according to the evidence based medicine (EBM) rules. We performed an exhaustive analysis of the literature, searching either in electronic databases or among the references of the identified articles (hand searching). We searched the MEDLINE computer database for reports from 1985 through January 2005 and selected for analysis the clinical trials conducted over adults affected by newly diagnosed AML aged less than 65 years. The study design had to satisfy strict methodological criteria and must consider global mortality and/or disease free survival as primary outcomes. Overall we found 7750 papers; by using the limits "clinical trial" as publication type, "all adults 19+ years", we were able to select 344 papers. Among these, a further selection was made, based on two main clinical queries: 1) is auto-SCT superior to ICC/no other therapy in improving DFS and/or OS in adult AML patients in first CR? 2) is allo-SCT superior to auto-SCT/other therapeutic options in improving DFS and/or OS in adult AML patients in first CR? Concerning the first query, a possible advantage of auto-SCT over ICC was not clearly supported by data from clinical trials; there is no evidence that auto-SCT is superior in terms of OS to chemotherapy. Nevertheless, the reported TRM has been significantly reduced within the past years. Thus, the percentage of patients suitable for auto-SCT in CR has increased. Moreover, the scarce data concerning the comparison between auto-SCT and chemotherapy in different subsets of patients are unable to suggest a differentiated approach in patients with high-risk, standard-risk or low-risk AML. Data from the literature show that patients with unfavorable risk disease are more often addressed to allo-SCT and patients with low-risk disease receive more often intensive consolidation chemotherapy. Concerning the second query, interpretation of data from the main prospective studies about the role of allo-SCT in previously untreated AML is not easy. The first problem is the lack of real randomized clinical trials; in fact, according to the reported studies, AML patients generally receive allo-SCT on the basis of donor availability (the so called "genetic randomization"). The second problem is the frequent absence of intention to treat analysis. Despite methodological limitations, it was possible to compare allo-SCT with auto-SCT on a donor versus no-donor analysis and within risk groups. No overall benefit of allo-grafting on survival was demonstrated by any trial. In conclusion, the EBM approach highlighted the limitations observed in the published studies concerning consolidation therapy in AML; some suggestions, emerging from non-randomized, as well as randomized studies, are adequate, but not conclusive. This point, coupled with the intrinsic complexity to study AML biological heterogeneity, is probably a major obstacle to draw conclusive evidences for consolidation therapy in AML. These observations should plan to address new randomized studies on AML therapy; however, due to the emergence of genetic subgroups and new drugs targeting specific abnormalities, these trials should probably be designed directly focusing on the single entities. In this way, the cure of AML could eventually become the cure of each specific AML subset with its peculiar biological, molecular and prognostic features.

译文

急性髓系白血病 (AML) 的缓解后治疗仍然存在问题。已证明,年轻患者在诱导治疗后可以通过积极的缓解后疗法维持更长的完全缓解 (CR): 异体 (allo),自体 (auto) 干细胞移植 (SCT) 或强化化疗 (ICC)。我们研究的目的是确定比较这三种治疗方案的最重要的随机和对照研究,以便根据循证医学 (EBM) 规则得出结论和可能的AML缓解后治疗建议。我们对文献进行了详尽的分析,在电子数据库中或在已识别文章的参考文献中进行搜索 (手工搜索)。我们在MEDLINE计算机数据库中搜索了通过2005年1月1985年的报告,并选择了针对年龄小于65岁的新诊断AML的成年人进行的临床试验进行分析。研究设计必须满足严格的方法学标准,并且必须将全球死亡率和/或无病生存率作为主要结果。总的来说,我们发现了7750篇论文; 通过使用限制 “临床试验” 作为出版类型,“所有成人19岁”,我们能够选择344篇论文。其中,基于两个主要的临床问题进行了进一步的选择: 1) 在改善首次CR的成年AML患者的DFS和/或OS方面,auto-SCT是否优于ICC/no其他疗法?2) 在改善首次CR的成年AML患者的DFS和/或OS方面,allo-SCT是否优于auto-SCT/其他治疗选择?关于第一个查询,临床试验数据并未明确支持auto-SCT优于ICC的可能优势; 没有证据表明auto-SCT在OS方面优于化疗。然而,在过去几年中,报告的TRM已大大减少。因此,CR中适合auto-SCT的患者百分比增加了。此外,关于不同患者亚组中auto-SCT和化疗之间比较的稀缺数据无法提示高风险,标准风险或低风险AML患者的差异化方法。来自文献的数据表明,患有不利风险疾病的患者更常接受allo-SCT治疗,而低风险疾病的患者更常接受强化强化化疗。关于第二个查询,对来自主要前瞻性研究的有关allo-SCT在先前未经治疗的AML中的作用的数据的解释并不容易。第一个问题是缺乏真正的随机临床试验; 实际上,根据报道的研究,AML患者通常根据供体的可用性接受allo-SCT (所谓的 “遗传随机化”)。第二个问题是经常缺乏治疗分析的意图。尽管方法上有局限性,但可以在供体分析与无供体分析以及风险组中比较allo-SCT与auto-SCT。任何试验都没有证明同种异体移植对生存率的总体益处。总之,EBM方法强调了在已发表的关于AML巩固治疗的研究中观察到的局限性; 从非随机和随机研究中提出的一些建议是足够的,但不是结论性的。这一点,加上研究AML生物异质性的内在复杂性,可能是为AML巩固治疗得出确凿证据的主要障碍。这些观察结果应计划解决有关AML治疗的新的随机研究; 但是,由于遗传亚组的出现和针对特定异常的新药的出现,这些试验可能应直接针对单个实体进行设计。这样,AML的治疗最终可以成为每个特定AML子集的治疗方法,具有其独特的生物学,分子和预后特征。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录