Ecological principle meets cancer treatment: treating children with acute myeloid leukemia with low-dose chemotherapy. Issue 3 (22nd January 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: National science review. Volume 6:Issue 3(2019)
• Page Start: 469
• Page End: 479
• Publication Date: 2019-01-22
• Subjects: low-dose chemotherapy -- acute myeloid leukemia -- G-CSF; Science -- Periodicals; 505
• DOI: 10.1093/nsr/nwz006
• Languages: English
• ISSNs: 2095-5138

Abstract

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.