Discontinuation of l-asparaginase and poor response to prednisolone are associated with poor outcome of ETV6-RUNX1-positive pediatric B-cell precursor acute lymphoblastic leukemia
Discontinuation of l-asparaginase and poor response to prednisolone are associated with poor outcome of ETV6-RUNX1-positive pediatric B-cell precursor acute lymphoblastic leukemia
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DOI：
10.1007/s12185-019-02599-w
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发表时间：
2019-04-01
影响因子：
2.1
通讯作者：
Horibe, Keizo
中科院分区：
文献类型：
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作者：
Usami, Ikuya;Imamura, Toshihiko;Horibe, Keizo
ETV 6-RUNX 1阳性前体B急性淋巴细胞白血病（B-ALL）是儿科B-ALL的一种常见亚型，在儿科B-ALL的当代临床试验中显示出良好的结局。因此，可以探讨降低治疗强度的可能性。这项前瞻性研究检查了205例ETV 6-RUNX 1阳性B-ALL儿童患者的结局，这些患者按照日本儿童白血病研究组协会（JACLS）ALL-02方案进行统一治疗。JACLS ALL-02方案未采用基于聚合酶链反应（PCR-MRD）的风险分层检测微小残留病;然而，4年无事件生存期（EFS）和总生存期（OS）分别为94.4 +/-1.6%和97.5 +/-1.1%。特别是，205例患者中有92例（44.9%）成功接受了强度较低的方案治疗，仅包括两个周期的高剂量甲氨蝶呤和一个疗程的再诱导治疗，包括长春新碱、L-天冬酰胺酶（L-asp）、吡拉托品和泼尼松龙。多变量分析显示，停用左旋门冬氨酸和对泼尼松龙反应差分别与EFS差相关（HR 6.3; 95% CI 1.3-27.0）和OS（人力资源17.5; 95% CI 2.3-130），这表明，如果包括PCR在内的风险分层系统，大多数ETV 6-RUNX 1阳性B-ALL病例可以通过强度较低的化疗方案治愈。避免了MRD监测和L-asp使用不足。
ETV6-RUNX1-positive B precursor acute lymphoblastic leukemia (B-ALL) is a common subtype of pediatric B-ALL that has shown excellent outcomes in contemporary clinical trials for pediatric B-ALL. Examinations of the possibility of reducing therapeutic intensity may thus be explored. This prospective study examined outcomes in 205 pediatric patients with ETV6-RUNX1-positive B-ALL uniformly treated following the Japan Association of Childhood Leukemia Study Group (JACLS) ALL-02 protocol. The JACLS ALL-02 protocol does not employ minimal residual disease detected by polymerase chain reaction (PCR-MRD)-based risk stratification; however, 4-year event-free survival (EFS) and overall survival (OS) were 94.4 +/- 1.6 and 97.5 +/- 1.1%, respectively. In particular, 92 of 205 (44.9%) patients were successfully treated with a less intensive regimen involving only two cycles of high dose methotrexate and one course of re-induction therapy comprising vincristine, l-asparaginase (L-asp), pirarubicin, and prednisolone. Multivariate analysis revealed that discontinuation of L-asp and poor response to prednisolone was, respectively, associated with poor EFS (HR 6.3; 95% CI 1.3-27.0) and OS (HR 17.5; 95% CI 2.3-130), suggesting that the majority of ETV6-RUNX1-positive B-ALL cases may be cured by a less-intensive chemotherapy regimen if the risk stratification system including PCR-MRD monitoring and insufficient use of L-asp is avoided.