Background: The FMS-like tyrosine kinase 3 (FLT3) gene mutated in 10–15% of pediatric acute myeloid leukemia (AML) is associated with an inferior outcome. The aim of the study was to analyze the outcome and characteristics of FLT3-ITD-positive pediatric AML. Methods: We retrospectively analyzed the nationwide pediatric AML database from between 2005 and 2022. FLT3-ITD was found in 54/497 (10.7%) patients with available analysis. Three consecutive treatment protocols were used (AML-BFM 2004 Interim, AML-BFM 2012 Registry, AML-BFM 2019 recommendations). Results: Probabilities of 5-year overall (OS), event-free (EFS) and relapse-free survival were significantly lower in the FLT3-ITD-positive patients compared to FLT3-ITD-negative (0.54 vs. 0.71,p= 0.041; 0.36 vs. 0.59,p= 0.0004; 0.47 vs. 0.70,p= 0.0029, accordingly). An improvement in the outcome was found in the analyzed period of time, with a trend of better survival in patients treated under the AML-BFM 2012 and AML-BFM 2019 protocols compared to the AML-BFM 2004 protocol (5-year EFS 0.52 vs. 0.27,p= 0.069). There was a trend of improved outcomes in patients treated with FLT3 inhibitors (n = 9, 2-year EFS 0.67 vs. 0.33,p= 0.053) and those who received stem cell transplantation (SCT) (n = 26; 5-year EFS 0.70 vs. 0.27,p= 0.059). The co-occurrence of the WT1 mutation had a dismal impact on the prognosis (5-year EFS 0.23 vs. 0.69,p= 0.002), while the NPM1 mutation improved survival (5-year OS 1.0 vs. 0.44,p= 0.036). Conclusions: It seems that SCT and FLT3 inhibitors have a beneficial impact on the prognosis. Additional genetic alterations, like the WT1 and NPM1 mutations, significantly influence the outcome.
背景：FMS样酪氨酸激酶3（FLT3）基因突变见于10-15%的儿童急性髓系白血病（AML）患者，与不良预后相关。本研究旨在分析FLT3-ITD阳性儿童AML的临床特征及治疗结局。方法：我们回顾性分析了2005年至2022年全国儿童AML数据库资料。在497例可评估患者中，54例（10.7%）检测到FLT3-ITD突变。研究期间依次采用三种治疗方案（AML-BFM 2004中期方案、AML-BFM 2012注册方案、AML-BFM 2019推荐方案）。结果：与FLT3-ITD阴性组相比，FLT3-ITD阳性组患者的5年总生存率（OS）、无事件生存率（EFS）和无复发生存率均显著降低（分别为0.54 vs. 0.71，p=0.041；0.36 vs. 0.59，p=0.0004；0.47 vs. 0.70，p=0.0029）。在研究时间范围内观察到治疗结局的改善趋势：与AML-BFM 2004方案相比，采用AML-BFM 2012和AML-BFM 2019方案治疗的患者生存率呈现更优趋势（5年EFS 0.52 vs. 0.27，p=0.069）。接受FLT3抑制剂治疗的患者（n=9，2年EFS 0.67 vs. 0.33，p=0.053）及接受干细胞移植（SCT）的患者（n=26，5年EFS 0.70 vs. 0.27，p=0.059）均显示出改善预后的趋势。WT1基因共突变对预后产生负面影响（5年EFS 0.23 vs. 0.69，p=0.002），而NPM1突变则改善生存（5年OS 1.0 vs. 0.44，p=0.036）。结论：干细胞移植和FLT3抑制剂可能对改善预后具有积极作用。WT1和NPM1等附加基因突变对治疗结局产生显著影响。
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