Ecological principle meets cancer treatment: treating children with acute myeloid leukemia with low-dose chemotherapy.
Ecological principle meets cancer treatment: treating children with acute myeloid leukemia with low-dose chemotherapy.
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生态原理遇上癌症治疗：小剂量化疗治疗儿童急性髓系白血病
DOI：
10.1093/nsr/nwz006
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发表时间：
2019-05
影响因子：
20.6
通讯作者：
Wang QF
中科院分区：
文献类型：
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作者：
Hu Y;Chen A;Zheng X;Lu J;He H;Yang J;Zhang Y;Sui P;Yang J;He F;Wang Y;Xiao P;Liu X;Zhou Y;Pei D;Cheng C;Ribeiro RC;Hu S;Wang QF
儿童急性髓性白血病（AML）缓解诱导的标准化疗方案与显著的发病率和死亡率相关。我们进行了一项队列研究，以确定降低缓解诱导化疗强度对选择的AML儿童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）治疗的结果的影响。接受LDC/G-CSF治疗的患者在两次诱导疗程后达到完全缓解（CR）的比例为87.0%（40/46）。所有患者均接受缓解后治疗，包括标准巩固和/或干细胞移植。在研究期间，另外94名连续接受标准化疗（SDC）诱导的AML患儿（80/94（85.1%）的患者在诱导II期后达到CR， P = 0.953）和缓解后。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 vs 70.7%, P = 0.99）和总生存率（70.3 vs 74.6%, P = 0.69）分别无显著差异。在第一个诱导疗程后，LDC/G-CSF组患者的白细胞（WBC）和血小板计数恢复明显快于SDC组（WBC恢复11.5 d比18.5 d, P < 0.001）；血小板为15.5 vs. 22.0 d (P < 0.001))。为了检验分子反应的质量，我们进行了靶向深度测序。在20例经两个疗程LDC/G-CSF （n = 9）或SDC （n = 11）治疗后达到血液学CR的儿童中，诊断时检测到137个突变，无论治疗组如何，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%）。总之，接受LDC/G-CSF治疗的AML患儿似乎具有相似的结局和突变清除率，但毒性明显低于接受SDC治疗的患儿。因此，应进一步评估LDC/G-CSF作为儿童AML缓解诱导的有效替代方案。
Abstract 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, P = 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%; P = 0.99) and overall (70.3 vs. 74.6%, P = 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 (P < 0.001); 15.5 vs. 22.0 d for platelets (P < 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 (n = 9) or SDC (n = 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.