NOTCH1 and FBXW7 mutations have a favorable impact on early response to treatment, but not on outcome, in children with T-cell acute lymphoblastic leukemia (T-ALL) treated on EORTC trials 58881 and 58951
NOTCH1 and FBXW7 mutations have a favorable impact on early response to treatment, but not on outcome, in children with T-cell acute lymphoblastic leukemia (T-ALL) treated on EORTC trials 58881 and 58951
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DOI：
10.1038/leu.2010.205
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发表时间：
2010-12-01
期刊：
影响因子：
11.4
通讯作者：
Cave, H.
中科院分区：
文献类型：
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作者：
Clappier, E.;Collette, S.;Cave, H.
T细胞急性淋巴细胞白血病（T-ALL）的风险调整治疗分层目前仅基于对化疗的早期反应。我们研究了入组EORTC-CLG试验的T-ALL儿童中NOTCH 1或FBXW 7突变导致的NOTCH通路过度活化的预后意义。总体而言，134例患者中有80例（60%）为NOTCH+（NOTCH 1和/或FBXW 7突变）。尽管临床表现与NOTCH状态无显著相关性，但根据前期“反应差”的比率，NOTCH+患者对化疗的早期反应优于NOTCH-患者。（25% vs 44%; P=0.02）和诱导完成时高微小残留病（MRD）水平的发生率（11%（7/62）vs 32%（10/31）; P=0.01）。然而，NOTCH+患者的结局与NOTCH-患者相似，5年无事件生存率（EFS）分别为73%和70%（P=0.82），5年总生存率分别为82%和79%（P=0.62）。在MRD水平高的患者中，5年EFS率为0%（NOTCH+）与42%（NOTCH-），而在MRD水平低的患者中，结局相似：76%（NOTCH+）与78%（NOTCH+）。在NOTCH+患者中，孤立性中枢神经系统（CNS）复发的发生率相对较高（8.3%），这可能与NOTCH+白血病原始细胞靶向CNS的倾向较高有关。Leukemia（2010）24，2023-2031; doi：10.1038/leu.2010.205; 2010年9月23日在线发表
Risk-adjusted treatment stratification in T-cell acute lymphoblastic leukemias (T-ALLs) is currently based only on early response to chemotherapy. We investigated the prognostic implication of hyperactivation of NOTCH pathway resulting from mutations of NOTCH1 or FBXW7 in children with T-ALL enrolled in EORTC-CLG trials. Overall, 80 out of 134 (60%) patients were NOTCH+ (NOTCH1 and/or FBXW7 mutated). Although clinical presentations were not significantly associated with NOTCH status, NOTCH+ patients showed a better early response to chemotherapy as compared with NOTCH- patients, according to the rate of poor pre-phase 'responders' (25% versus 44%; P=0.02) and the incidence of high minimal residual disease (MRD) levels (11% (7/62) versus 32% (10/31); P=0.01) at completion of induction. However, the outcome of NOTCH+ patients was similar to that of NOTCH- patients, with a 5-year event-free survival (EFS) of 73% and 70% (P=0.82), and 5-year overall survival of 82% and 79% (P=0.62), respectively. In patients with high MRD levels, the 5-year EFS rate was 0% (NOTCH+) versus 42% (NOTCH-), whereas in those with low MRD levels, the outcome was similar: 76% (NOTCH+) versus 78% (NOTCH+). The incidence of isolated central nervous system (CNS) relapses was relatively high in NOTCH+ patients (8.3%), which could be related to a higher propensity of NOTCH+ leukemic blasts to target the CNS. Leukemia (2010) 24, 2023-2031; doi:10.1038/leu.2010.205; published online 23 September 2010