Ecological principle meets cancer treatment: treating children with acute myeloid leukemia with low-dose chemotherapy.
Yixin HuAili ChenXinchang ZhengJun LuHailong HeJin YangYa ZhangPinpin SuiJingyi YangFuhong HeYi WangPeifang XiaoXin LiuYinmei ZhouDeqing PeiCheng ChengRaul C RibeiroShaoyan HuQian-Fei WangPublished in: National science review (2019)
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.
Keyphrases
- acute myeloid leukemia
- low dose
- young adults
- stem cell transplantation
- high dose
- allogeneic hematopoietic stem cell transplantation
- end stage renal disease
- newly diagnosed
- locally advanced
- chronic kidney disease
- cerebrospinal fluid
- patient reported outcomes
- single cell
- radiation therapy
- climate change
- rectal cancer
- acute lymphoblastic leukemia
- human health
- high intensity
- replacement therapy