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Genetic Features and Efficacy of Decitabine-Based Chemotherapy in Elderly Patients with Acute Myeloid Leukemia

44 Pages Posted: 21 Sep 2018

See all articles by Bianhong Wang

Bianhong Wang

Tsinghua University - Beijing Tsinghua Changgung Hospital; Government of the People's Republic of China - Chinese General PLA Hospital

Na Lv

Government of the People's Republic of China - Chinese General PLA Hospital

Ting Li

Annoroad Gene Technology

Lili Wang

Government of the People's Republic of China - Chinese General PLA Hospital

Yu Jing

Government of the People's Republic of China - Chinese General PLA Hospital

Jing Guo

Annoroad Gene Technology

Chongjian Chen

Annoroad Gene Technology

Yonghui Li

Government of the People's Republic of China - Chinese General PLA Hospital

Li Yu

Government of the People's Republic of China - Department of Hematology

More...

Abstract

The outcome of elderly acute myeloid leukemia (AML) patients is poor, which was traditionally attributed to patient- and leukemia-related factors. However, studies about the genetic features of these elderly patients have not been integrated and the genetic mechanism of their poor outcome is less known. Here, we used next generation sequencing (NGS) to identify the genetic features of elderly AML patients and confirmed the efficacy of chemotherapy based on molecular aberrations. Mutations in 111 genes relevant to hematological malignancy was analysed by virture of NGS and the genetic differences were compared between elderly (n=52) and young (n=161) AML patients. Furthermore, the outcome of decitabine-based chemotherapy was identified in elderly patients. Results showed that frequencies of adverse genetic alterations, such as RUNX1 and secondary-type mutations (ASXL1, STAG2 and spliceosome), were much higher in elderly patients, while the frequency of WT1 mutations was much lower. Moreover, epigenetic mutations such as DNMT3A, TET2, ASXL1 and IDH2, were also more common in elderly patients. Furthermore, there were 39 elderly patients receiving the decitabine-based chemotherapy, and the results showed that the overall response rate (ORR) and complete remission rate (CR) were 76.9% and 59%, respectively, after the first cycle. The median overall survival (OS) for those older patients was 12 months, and the 2-year OS probability was 20.5%. Our study provides deep understanding into the molecular mechanisms of the poor outcome of elderly AML patients. Epigenetic mutations play an important role, and decitabine-based regimen can be used as alternative first-line chemotherapy for elderly patients.

Funding Statement: This study is funded by the National Natural Science Foundation of China (81670162, 81170518, 81470010 and 81370635), Capital Medical Development Scientific Research Fund (SF2001-5001-07) and the capital of the public health project (Z111107067311070).

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: Our study was approved by the Human Ethics Committees of the Chinese PLA General Hospital, and all patients provided written informed consent before they received chemotherapy.

Keywords: acute myeloid leukemia, next generation sequencing, mutational analysis, decitabine-based chemotherapy, clinical outcome

Suggested Citation

Wang, Bianhong and Lv, Na and Li, Ting and Wang, Lili and Jing, Yu and Guo, Jing and Chen, Chongjian and Li, Yonghui and Yu, Li, Genetic Features and Efficacy of Decitabine-Based Chemotherapy in Elderly Patients with Acute Myeloid Leukemia (December 8, 2018). Available at SSRN: https://ssrn.com/abstract=3234804

Bianhong Wang (Contact Author)

Tsinghua University - Beijing Tsinghua Changgung Hospital ( email )

Beijing, 100084
China

Government of the People's Republic of China - Chinese General PLA Hospital ( email )

Beijing, 100853
China

Na Lv

Government of the People's Republic of China - Chinese General PLA Hospital

Beijing, 100853
China

Ting Li

Annoroad Gene Technology

Beijing, 100176
China

Lili Wang

Government of the People's Republic of China - Chinese General PLA Hospital

Beijing, 100853
China

Yu Jing

Government of the People's Republic of China - Chinese General PLA Hospital

Beijing, 100853
China

Jing Guo

Annoroad Gene Technology

Beijing, 100176
China

Chongjian Chen

Annoroad Gene Technology

Beijing, 100176
China

Yonghui Li

Government of the People's Republic of China - Chinese General PLA Hospital

Beijing, 100853
China

Li Yu

Government of the People's Republic of China - Department of Hematology ( email )

28 Fuxing Road
Beijing, 100853
United States

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