ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: improved outcome with contemporary therapy.
ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: improved outcome with contemporary therapy.
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作者：
ETV 6-RUNX 1融合是儿童急性淋巴细胞白血病（ALL）中最常见的遗传畸变。为了评价这种药物敏感性白血病的结局是否通过当代风险导向治疗得到改善，我们研究了168例新诊断ETV 6-RUNX 1阳性ALL儿童的临床特征、反应和不良事件，这些儿童参加了圣犹达全方位治疗研究XIIIA（N=36）、XIIIB（N=38）和XV（N=94）。结果与494例ETV 6-RUNX 1阴性前体B细胞ALL患者进行了比较。ETV 6-RUNX 1与年龄1-9岁、治疗前分类为低风险和治疗第19天较低水平的微小残留病（MRD）相关（p<0.001）。在总XIIIA或XIIIB中，有或无ETV 6-RUNX 1的患者之间的无事件生存期（EFS）或总生存期（OS）无差异。相比之下，在Total XV中，ETV 6-RUNX 1患者的EFS（p=0.04; 5年估计值，96.8±2.4% vs 88.3±2.5%）和OS（p=0.04; 98.9±1.4% vs 93.7±1.8%）显著优于未接受ETV 6-RUNX 1的患者。在ETV 6-RUNX 1组中，与较高OS相关的唯一显著预后因素是治疗方案Total XV（与XIIIA或XIIIB相比）（p=0.01）。因此，在Total XV研究中，MRD指导的治疗方案（包括强化天冬酰胺酶和高剂量甲氨蝶呤）产生的结局显著优于既往方案，并证明几乎所有ETV 6-RUNX 1 ALL儿童均可治愈。
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 to 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.
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影响因子：
20.3
作者：
Borkhardt, A;Cazzaniga, G;Biondi, A
通讯作者：
Biondi, A
影响因子：
3.7
作者：
Mathew, S;Shurtleff, SA;Raimondi, SC
通讯作者：
Raimondi, SC
影响因子：
64.8
作者：
Mullighan, Charles G.;Goorha, Salil;Downing, James R.
通讯作者：
Downing, James R.
DOI：
10.1073/pnas.92.11.4917
发表时间：
1995-05-23
影响因子：
11.1
作者：
GOLUB, TR;BARKER, GF;GILLILAND, DG
通讯作者：
GILLILAND, DG
影响因子：
20.3
作者：
Morrow, M;Horton, S;Williams, O
通讯作者：
Williams, O