Hu Yixin, Chen Aili, Zheng Xinchang, Lu Jun, He Hailong, Yang Jin, Zhang Ya, Sui Pinpin, Yang Jingyi, He Fuhong, Wang Yi, Xiao Peifang, Liu Xin, Zhou Yinmei, Pei Deqing, Cheng Cheng, Ribeiro Raul C, Hu Shaoyan, Wang Qian-Fei
Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou 215025, China.
CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
Natl Sci Rev. 2019 May;6(3):469-479. doi: 10.1093/nsr/nwz006. Epub 2019 Jan 22.
Standard chemotherapy regimens for remission induction of pediatric acute myeloid leukemia (AML) are associated with significant morbidity and mortality. We performed a cohort study to determine the impact of reducing the intensity of remission induction chemotherapy on the outcomes of selected children with AML treated with a low-dose induction regimen plus granulocyte colony stimulating factor (G-CSF) (low-dose chemotherapy (LDC)/G-CSF). Complete response (CR) after two induction courses was attained in 87.0% (40/46) of patients receiving LDC/G-CSF. Post-remission therapy was offered to all patients, and included standard consolidation and/or stem cell transplantation. During the study period, an additional 94 consecutive children with AML treated with standard chemotherapy (SDC) for induction (80/94 (85.1%) of the patients attained CR after induction II, = 0.953) and post-remission. In this non-randomized study, there were no significant differences in 4-year event-free (67.4 vs. 70.7%; = 0.99) and overall (70.3 vs. 74.6%, = 0.69) survival in the LDC/G-CSF and SDC cohorts, respectively. After the first course of induction, recovery of white blood cell (WBC) and platelet counts were significantly faster in patients receiving LDC/G-CSF than in those receiving SDC (11.5 vs. 18.5 d for WBCs ( < 0.001); 15.5 vs. 22.0 d for platelets ( < 0.001)). To examine the quality of molecular response, targeted deep sequencing was performed. Of 137 mutations detected at diagnosis in 20 children who attained hematological CR after two courses of LDC/G-CSF ( = 9) or SDC ( = 11), all of the mutations were below the reference value (variant allelic frequency <2.5%) after two courses, irrespective of the treatment group. In conclusion, children with AML receiving LDC/G-CSF appear to have similar outcomes and mutation clearance levels, but significantly lower toxicity than those receiving SDC. Thus, LDC/G-CSF should be further evaluated as an effective alternative to remission induction in pediatric AML.
用于小儿急性髓系白血病（AML）缓解诱导的标准化疗方案会带来显著的发病率和死亡率。我们开展了一项队列研究，以确定降低缓解诱导化疗强度对部分接受低剂量诱导方案加粒细胞集落刺激因子（G-CSF）（低剂量化疗（LDC）/G-CSF）治疗的AML患儿预后的影响。接受LDC/G-CSF治疗的患者中，87.0%（40/46）在两个诱导疗程后达到完全缓解（CR）。所有患者均接受缓解后治疗，包括标准巩固治疗和/或干细胞移植。在研究期间，另有94例连续的AML患儿接受标准化疗（SDC）进行诱导治疗（80/94（85.1%）的患者在诱导治疗II后达到CR，P = 0.953）以及缓解后治疗。在这项非随机研究中，LDC/G-CSF组和SDC组的4年无事件生存率（67.4%对70.7%；P = 0.99）和总生存率（70.3%对74.6%，P = 0.69）分别无显著差异。在第一个诱导疗程后，接受LDC/G-CSF治疗的患者白细胞（WBC）和血小板计数的恢复明显快于接受SDC治疗的患者（WBC为11.5天对18.5天（P < 0.001）；血小板为15.5天对22.0天（P < 0.001））。为了检测分子反应的质量，进行了靶向深度测序。在20例接受两个疗程LDC/G-CSF（n = 9）或SDC（n = 11）治疗后达到血液学CR的患儿中，诊断时检测到137个突变，两个疗程后所有突变均低于参考值（变异等位基因频率<2.5%），与治疗组无关。总之，接受LDC/G-CSF治疗的AML患儿似乎有相似的预后和突变清除水平，但毒性明显低于接受SDC治疗的患儿。因此，LDC/G-CSF应作为小儿AML缓解诱导的有效替代方案进一步评估。
