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Poor outcome of pediatric patients with acute myeloid leukemia harboring high FLT3/ITD allelic ratios
Nature Communications ( IF 14.7 ) Pub Date : 2022-06-27 , DOI: 10.1038/s41467-022-31489-9
Kun-Yin Qiu 1, 2 , Xiong-Yu Liao 1, 2 , Yong Liu 1, 2, 3 , Ke Huang 1, 2 , Yang Li 1, 2 , Jian-Pei Fang 1, 2 , Dun-Hua Zhou 1, 2
Affiliation  

Activating FLT3 mutations are the most common mutations in acute myeloid leukemia (AML), but the optimal threshold of FLT3/ITD allelic ratio (AR) among pediatric AML patients remains controversial. Here, we present the outcome and prognostic significance of FLT3/ITD AR analysis among pediatric patients with AML from the TARGET dataset. Applying fitting curve models and threshold effect analysis using the restrictive cubic spline function following Cox proportional hazards models identifies the cut-off value of 0.5 on FLT3/ITD AR. Moreover, we observe that high FLT3/ITD AR patients have an inferior outcome when compared to low AR patients. Our study also demonstrates that stem cell transplantation may improve the outcome in pediatric AML patients with high FLT3/ITD AR and may be further improved when combined with additional therapies such as Gemtuzumab Ozogamicin. These findings underline the importance of individualized treatment of pediatric AML.



中文翻译:

具有高 FLT3/ITD 等位基因比率的儿童急性髓性白血病患者预后不良

激活 FLT3 突变是急性髓性白血病 (AML) 中最常见的突变,但儿童 AML 患者中 FLT3/ITD 等位基因比率 (AR) 的最佳阈值仍存在争议。在这里,我们展示了来自 TARGET 数据集的儿童 AML 患者的 FLT3/ITD AR 分析的结果和预后意义。使用 Cox 比例风险模型后的限制性三次样条函数应用拟合曲线模型和阈值效应分析确定 FLT3/ITD AR 的截止值 0.5。此外,我们观察到,与低 AR 患者相比,高 FLT3/ITD AR 患者的结果较差。我们的研究还表明,干细胞移植可能会改善 FLT3/ITD AR 高的儿科 AML 患者的预后,并且在与其他疗法(如 Gemtuzumab Ozogamicin)联合使用时可能会进一步改善。这些发现强调了儿童 AML 个体化治疗的重要性。

更新日期:2022-06-27
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