The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials
The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials
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DOI：
10.1182/blood.v98.6.1752
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发表时间：
2001-09-15
期刊：
影响因子：
20.3
通讯作者：
Linch, DC
中科院分区：
文献类型：
--
作者：
Kottaridis, PD;Gale, RE;Linch, DC
在急性髓性白血病（AML）中，除了细胞遗传学之外，还需要进一步的预后决定因素来预测复发风险增加的患者。最近的研究表明，FLT 3基因中的内部串联重复（ITD）可能会对临床结果产生不利影响。本研究评价了FLT 3/ITD突变对854例患者结局的影响，这些患者大多数年龄在60岁或以下，在英国医学研究理事会（MRC）AML试验中接受治疗。27%的患者存在FLT 3/ITD突变，并与白细胞增多和高比例的骨髓原始细胞相关（两者均P <0.001）。它与较低的完全缓解率（P = 0.05）和较高的诱导死亡率（P = 0.04）存在临界相关性，并与复发风险（RR）、无不良疾病生存期（DFS）、无事件生存期（EFS）和总生存期（OS）增加相关（所有P <0.001）。在多变量分析中，突变的存在是预测RR和DFS的最重要的预后因素（P < .0001），并且对于OS（P = .009）和EFS（P = .002）仍然有意义。没有证据表明FLT 3/ITD的相对效应在细胞遗传学风险组之间存在差异。在23%的FLT 3/ITD+患者中检测到一种以上的突变，并与OS（P = 0.04）和EFS（P = 0.07）更差相关。在10%的FLT 3/ITD+患者中存在双等位基因疾病或野生型等位基因的部分/完全丢失。建议将FLT 3/ITD检测作为诊断时的常规检测，并评估治疗管理。
In acute myeloid leukemia (AML), further prognostic determinants are required in addition to cytogenetics to predict patients at increased risk of relapse. Recent studies have indicated that an internal tandem duplication (ITD) in the FLT3 gene may adversely affect clinical outcome. This study evaluated the impact of a FLT3/ITD mutation on outcome in 854 patients, mostly 60 years of age or younger, treated in the United Kingdom Medical Research Council (MRC) AML trials. An FLT3/ITD mutation was present in 27% of the patients and was associated with leukocytosis and a high percentage of bone marrow blast cells (P < .001 for both). It had a borderline association with a lower complete remission rate (P = .05) and a higher induction death rate (P = .04), and was associated with increased relapse risk (RR), adverse disease-free survival (DFS), event-free survival (EFS), and overall survival (OS) (P < .001 for all). In multivariate analysis, presence of a mutation was the most significant prognostic factor predicting RR and DFS (P < .0001) and was still significant for OS (P = .009) and EFS (P = .002). There was no evidence that the relative effect of a FLT3/ITD differed between the cytogenetic risk groups. More than one mutation was detected in 23% of FLT3/ITD+ patients and was associated with worse OS (P = .04) and EFS (P = .07). Biallelic disease or partial/complete loss of wild-type alleles was present in 10% of FLT3/ITD+ patients. The suggestion is made that detection of a FLT3/ITD should be included as a routine test at diagnosis and evaluated for therapeutic management.