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.
儿童急性髓系白血病（AML）的标准缓解诱导化疗方案常伴随显著的发病率与死亡率。本研究通过队列分析，评估降低缓解诱导化疗强度对特定儿童AML患者的影响，该方案采用低剂量诱导化疗联合粒细胞集落刺激因子（G-CSF）（即低剂量化疗/G-CSF方案）。在接受低剂量化疗/G-CSF治疗的患者中，两个诱导疗程后完全缓解率达87.0%（40/46）。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。研究期间另有94例连续入组的儿童AML患者接受标准化疗进行诱导及缓解后治疗（其中80/94例（85.1%）在第二诱导疗程后达到完全缓解，P=0.953）。在这项非随机研究中，低剂量化疗/G-CSF组与标准化疗组的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）均无显著差异。首个诱导疗程后，低剂量化疗/G-CSF组患者的白细胞和血小板计数恢复时间显著短于标准化疗组（白细胞：11.5天对18.5天，P<0.001；血小板：15.5天对22.0天，P<0.001）。通过靶向深度测序评估分子反应质量发现：在20例经两个疗程低剂量化疗/G-CSF（9例）或标准化疗（11例）达到血液学完全缓解的患儿中，诊断时检测到的137个突变在治疗后均低于参考值（变异等位基因频率<2.5%），且该结果与治疗分组无关。综上所述，接受低剂量化疗/G-CSF治疗的儿童AML患者似乎具有与标准化疗相似的疗效和突变清除水平，且治疗毒性显著降低。因此，低剂量化疗/G-CSF方案值得作为儿童AML缓解诱导的有效替代方案进行进一步评估。
肿瘤(癌症)患者之家