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

Yixin Hu; Aili Chen; Xinchang Zheng; Jun Lu; Hailong He; Jin Yang; Ya Zhang; Pinpin Sui; Jingyi Yang; Fuhong He; Yi Wang; Peifang Xiao; Xin Liu; Yinmei Zhou; Deqing Pei; Cheng Cheng; Raul C Ribeiro; Shaoyan Hu; Qian-Fei Wang

doi:10.1093/nsr/nwz006

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

Natl Sci Rev. 2019 May;6(3):469-479. doi: 10.1093/nsr/nwz006. Epub 2019 Jan 22.

Authors

Yixin Hu¹, Aili Chen², Xinchang Zheng^{2

3}, Jun Lu¹, Hailong He¹, Jin Yang^{1

4}, Ya Zhang^{2

3}, Pinpin Sui^{2

3}, Jingyi Yang^{2

3}, Fuhong He², Yi Wang¹, Peifang Xiao¹, Xin Liu^{2

3}, Yinmei Zhou⁵, Deqing Pei⁵, Cheng Cheng⁵, Raul C Ribeiro⁶, Shaoyan Hu¹, Qian-Fei Wang^{2

3}

Affiliations

¹ Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou 215025, China.
² CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
³ University of Chinese Academy of Sciences, Beijing 100049, China.
⁴ Department of Pediatrics, Nothern Jiangsu People's Hospital, Yangzhou 225001, China.
⁵ Department of Biostatistics, St. Jude Children's Research Hospital, Memphis TN 38105, USA.
⁶ Department of Oncology and Global Medicine, International Outreach Program, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

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.

Keywords: G-CSF; acute myeloid leukemia; low-dose chemotherapy.