Response-guided chemotherapy for pediatric acute myeloid leukemia without hematopoietic stem cell transplantation in first complete remission: Results from protocol DB AML-01
Response-guided chemotherapy for pediatric acute myeloid leukemia without hematopoietic stem cell transplantation in first complete remission: Results from protocol DB AML-01
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DOI：
10.1002/pbc.27605
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发表时间：
2019-05-01
影响因子：
3.2
通讯作者：
de Bont, Eveline
中科院分区：
文献类型：
--
作者：
De Moerloose, Barbara;Reedijk, Ardine;de Bont, Eveline
急性髓性白血病（AML）患儿采用高剂量阿糖胞苷和蒽环类药物治疗，部分患儿采用造血干细胞移植（allo-HSCT），其存活率为70%。在这项多中心荷兰-比利时方案（DB AML-01）中，纳入了112例初治AML儿童。根据第一个诱导疗程后第15天的骨髓应答对治疗进行分层。反应差者立即接受第二个疗程，而反应好者则等待血液学恢复。两个诱导疗程后达到CR的患者在CR 1中继续接受三个巩固疗程，未接受HSCT。结果总缓解率为93.5%。中位随访4.1年后，3年无事件生存率（EFS）为52.6%（95%CI，42.9%-61.3%），3年累积复发率为39.7%（95%CI，30.1%-49.0%），3年总生存率（OS）为74.0%（95%CI，64.8%-81.2%）。在诊断时WBC高或FLT 3-ITD/NPM 1-WT的患者中发生的事件显著更多，而核心结合因子（CBF）白血病的EFS显著更好。结论DB AML-01反应指导治疗可获得良好的OS，特别是对于CBF白血病儿童、小于10岁儿童或初始WBC计数低于100 x 10（9）/L的儿童。FLT 3-ITD/NPM 1-WT患者的结局仍然较差，需要替代治疗策略。
Background Children with acute myeloid leukemia (AML) have a 70% survival rate with treatment regimens containing high doses of cytarabine and anthracyclines and, in some, hematopoietic stem cell transplantation (allo-HSCT). Procedure In this multicenter Dutch-Belgian protocol (DB AML-01), 112 children with de novo AML were included. Treatment was stratified according to day 15 bone marrow response after the first induction course. Poor responders received a second course without delay while good responders awaited hematological recovery. Patients achieving CR after two induction courses continued with three consolidation courses without HSCT in CR1. Results The overall remission rate was 93.5%. After a median follow-up of 4.1 years, three-year event-free survival (EFS) was 52.6% (95% CI, 42.9%-61.3%), three-year cumulative incidence of relapse 39.7% (95% CI, 30.1%-49.0%), and three-year overall survival (OS) 74.0% (95% CI, 64.8%-81.2%). Significantly more events occurred in patients with high WBC at diagnosis or FLT3-ITD/NPM1-WT, whereas core binding factor (CBF) leukemia had a significantly better EFS. KMT2A rearrangements and age > 10 years negatively impacted OS. Conclusions DB AML-01 response-guided therapy results in a favorable OS, particularly for children with CBF leukemia, children younger than 10 years or with initial WBC counts below 100 x 10(9)/L. Outcome of patients with FLT3-ITD/NPM1-WT remains poor and warrants alternative treatment strategies.