Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Leukemia. 2012 Feb;26(2):265-70. doi: 10.1038/leu.2011.227. Epub 2011 Aug 26.
ETV6-RUNX1 fusion is the most common genetic aberration in childhood acute lymphoblastic leukemia (ALL). To evaluate whether outcomes for this drug-sensitive leukemia are improved by contemporary risk-directed therapy, we studied clinical features, response and adverse events of 168 children with newly diagnosed ETV6-RUNX1-positive ALL on St Jude Total Therapy studies XIIIA (N=36), XIIIB (N=38) and XV (N=94). Results were compared with 494 ETV6-RUNX1-negative B-precursor ALL patients. ETV6-RUNX1 was associated with age 1-9 years, pre-treatment classification as low risk and lower levels of minimal residual disease (MRD) on day 19 of therapy (P<0.001). Event-free survival (EFS) or overall survival (OS) did not differ between patients with or without ETV6-RUNX1 in Total XIIIA or XIIIB. By contrast, in Total XV, patients with ETV6-RUNX1 had significantly better EFS (P=0.04; 5-year estimate, 96.8±2.4% versus 88.3±2.5%) and OS (P=0.04; 98.9±1.4% versus 93.7±1.8%) than those without ETV6-RUNX1. Within the ETV6-RUNX1 group, the only significant prognostic factor associated with higher OS was the treatment protocol Total XV (versus XIIIA or XIIIB) (P=0.01). Thus, the MRD-guided treatment schema including intensive asparaginase and high-dose methotrexate in the Total XV study produced significantly better outcomes than previous regimens and demonstrated that nearly all children with ETV6-RUNX1 ALL can be cured.
ETV6-RUNX1 融合是儿童急性淋巴细胞白血病（ALL）中最常见的遗传异常。为了评估针对这种药物敏感型白血病的当代风险导向治疗是否改善了预后，我们研究了 168 例新诊断的 ETV6-RUNX1 阳性 ALL 患儿在圣裘德全病程研究 XIIIA（n=36）、XIIIB（n=38）和 XV（n=94）中的临床特征、反应和不良事件。结果与 494 例 ETV6-RUNX1 阴性 B 前体 ALL 患者进行了比较。ETV6-RUNX1 与年龄 1-9 岁、治疗前低危分类和治疗第 19 天的微小残留病（MRD）水平较低相关（P<0.001）。在 Total XIIIA 或 XIIIB 中，无论是否存在 ETV6-RUNX1，患者的无事件生存（EFS）或总生存（OS）均无差异。相比之下，在 Total XV 中，ETV6-RUNX1 阳性患者的 EFS（P=0.04；5 年估计值为 96.8±2.4%对 88.3±2.5%）和 OS（P=0.04；98.9±1.4%对 93.7±1.8%）显著优于 ETV6-RUNX1 阴性患者。在 ETV6-RUNX1 组中，与更高 OS 唯一相关的显著预后因素是 Total XV 治疗方案（与 XIIIA 或 XIIIB 相比）（P=0.01）。因此，包括 Total XV 研究中强化门冬酰胺酶和大剂量甲氨蝶呤在内的基于 MRD 的治疗方案显著改善了预后，证明了几乎所有 ETV6-RUNX1 ALL 患儿都可以治愈。
