Next-generation sequencing revealed factors associated with cumulative incidence of relapse and leukemia-free survival in patients with newly diagnosed acute myeloid leukemia

Sai Huang; Peng Chen; Lu Wang; Lingmin Xu; Mingyu Jia; Jing Chen; Nan Wang; Fei Li; Lixia Liu; Jiayue Qin; Chengcheng Wang; Shanbo Cao; Liping Dou; Daihong Liu

doi:10.1016/j.cpt.2022.09.003

Next-generation sequencing revealed factors associated with cumulative incidence of relapse and leukemia-free survival in patients with newly diagnosed acute myeloid leukemia

Cancer Pathog Ther. 2022 Sep 27;1(1):25-32. doi: 10.1016/j.cpt.2022.09.003. eCollection 2023 Jan.

Authors

Sai Huang^{1

2}, Peng Chen^{1

3}, Lu Wang⁴, Lingmin Xu⁴, Mingyu Jia⁴, Jing Chen⁴, Nan Wang^{3

4}, Fei Li⁴, Lixia Liu⁵, Jiayue Qin⁵, Chengcheng Wang⁵, Shanbo Cao⁵, Liping Dou¹, Daihong Liu^{1

2}

Affiliations

¹ Department of Hematology, Senior Department of Hematology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China.
² National Clinical Research Center of Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China.
³ Chinese PLA Medical School, Beijing 100853, China.
⁴ Department of Hematology, The First Medical Center of PLA General Hospital, Beijing 100853, China.
⁵ Acornmed Biotechnology Co., Ltd., Tianjin 301700, China.

Abstract

Background: Several prognostic biomarkers have been validated for acute myeloid leukemia (AML), a heterogeneous hematopoietic malignancy. However, the factors associated with the cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) in real-world patients with AML have not been well defined.

Methods: This study examined clinical and mutational data of 246 patients with newly diagnosed AML who received the traditional "3 + 7" regimen in PLA General Hospital from January 2008 to August 2020. Factors associated with CIR and LFS in patients newly diagnosed with AML were analyzed using next-generation sequencing.

Results: Additional sex combs-like 1 (ASXL1) and Serine/arginine-rich splicing factor 2 (SRSF2) mutations were found to be associated with an increased risk of CIR and a reduced LFS in univariate analysis, while only SRSF2 mutations were associated with these factors in the multivariate analysis. Hyperleukocytosis maintained an independent effect on LFS in the multivariate analysis. Hematopoietic stem cell transplantation conferred a significant prognostic benefit on both CIR and LFS in our cohort. Furthermore, we validated the risk classification of patients with AML receiving traditional induction regimens across a broad age range. Based on next-generation sequencing results, we concluded that SRSF2 mutations were predictive of an increased risk of relapse, inferior LFS rates, and non-relapse mortality in patients with newly diagnosed AML.

Conclusion: These findings indicate that patients with SRSF2 mutations might not benefit from the conventional "3 + 7" regimen. Our results may help in developing molecular stratification strategies and could guide treatment decisions for patients with newly diagnosed AML.

Keywords: Acute myeloid leukemia; Induction regimen; Next-generation sequencing; Prognostic impact.