Ecological principle meets cancer treatment: treating children with acute myeloid leukemia with low-dose chemotherapy

• 来源期刊: 国家科学评论（英文版）
• 年，卷（期）: 2019,（3）
• 页码范围: 469-479
• 页数: 11页
• 语种: 英文
• DOI: 10.1093/nsr/nwz006

摘要

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 CRafter two courses ofLDC/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.