Niktoreh Naghmeh, Walter Christiane, Zimmermann Martin, von Neuhoff Christine, von Neuhoff Nils, Rasche Mareike, Waack Katharina, Creutzig Ursula, Hanenberg Helmut, Reinhardt Dirk
Department of Pediatrics III, University Children's Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.
Department of Pediatric Hematology and Oncology, Hannover Medical School, 30625 Hannover, Germany.
J Oncol. 2019 Jul 30;2019:1609128. doi: 10.1155/2019/1609128. eCollection 2019.
Acute myeloid leukemia is a life-threatening malignancy in children and adolescents treated predominantly by risk-adapted intensive chemotherapy that is partly supported by allogeneic stem cell transplantation. Mutations in the gene and fusion are predictors of poor survival outcome/prognosis that frequently occur in combination with internal tandem duplications of the juxta-membrane domain of ( To re-evaluate the effect of these factors in contemporary protocols, 353 patients (<18 years) treated in Germany with AML-BFM treatment protocols between 2004 and 2017 were included. Presence of mutated and in blasts (n=19) resulted in low 3-year event-free survival of 29% and overall survival of 33% compared to rates of 45-63% and 67-87% in patients with only one (only only mutation; n=29) or none of these mutations (n=272). Including and high allelic ratio (AR) of (AR ≥0.4) in the analysis revealed very poor outcomes for patients with co-occurrence of all three factors or any of double combinations. All these patients (n=15) experienced events and the probability of overall survival was low (27%). We conclude that co-occurrence of mutation, and with an AR ≥0.4 as triple or double mutations still predicts dismal response to contemporary first- and second-line treatment for pediatric acute myeloid leukemia.
急性髓系白血病是儿童和青少年中一种危及生命的恶性肿瘤，主要通过风险适应性强化化疗进行治疗，异基因干细胞移植为其提供了部分支持。 基因中的突变和 融合是生存结果/预后不良的预测指标，这些情况经常与 的近膜结构域内部串联重复同时出现（为了重新评估这些因素在当代治疗方案中的作用，纳入了2004年至2017年间在德国接受AML - BFM治疗方案治疗的353例（<18岁）患者。原始细胞中存在突变的 和 （n = 19）导致3年无事件生存率低至29%，总生存率为33%，而仅有一种（仅 或仅 突变；n = 29）或无这些突变（n = 272）的患者的这两个比率分别为45 - 63%和67 - 87%。在分析中纳入 和 高等位基因比率（AR）（AR≥0.4）显示，同时出现所有三个因素或任何双重组合的患者预后非常差。所有这些患者（n = 15）都经历了事件，总生存概率很低（27%）。我们得出结论， 突变、 和 AR≥0.4同时出现作为三重或双重突变仍然预示着儿童急性髓系白血病对当代一线和二线治疗的反应不佳。
