Clinical significance of next-generation sequencing technology for monitoring molecular minimal residual disease in acute myeloid leukemia
10.3760/cma.j.issn.1009-9921.2019.10.001
- VernacularTitle: 二代测序技术监测急性髓系白血病患者骨髓分子微小残留病的临床意义
- Author:
Dian LOU
1
;
Wenqing WANG
;
Guohui LI
;
Ren'an CHEN
;
Weiwei QIN
;
Ying LIU
;
Yangping ZHANG
;
Wen FAN
;
Li LIU
Author Information
1. Department of Hematology, Tangdu Hospital, Air Force Military Medical University, Xi'an 710038, China
- Publication Type:Journal Article
- Keywords:
Leukemia, myeloid, acute;
Bone marrow;
Sequence analysis, DNA;
Neoplasm, residual;
Minimal residual disease
- From:
Journal of Leukemia & Lymphoma
2019;28(10):577-581
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the value of next-generation sequencing (NGS) technology in the prognosis monitoring and treatment guidance for molecular minimal residual disease (MRD) in acute myeloid leukemia (AML) patients with complete remission (CR).
Methods:The clinical data of 68 AML (non-acute promyelocytic leukemia) patients who received gene mutation spectrum by using NGS technology at initial diagnosis and in CR phase in Tangdu Hospital of Air Force Military Medical University from January 2016 to July 2018 were retrospectively analyzed. The recurrence and survival of both molecular MRD positive group and negative group were analyzed and compared, and the value of NGS technology and multiparameter flow cytometry (MFC) were also analyzed in MRD monitoring.
Results:There were 39 males (57.4%) and 29 females (42.6%) in 68 patients, and the median age was 52 years old (8-82 years old). Molecular MRD positive group included 38 patients, while negative group included 30 patients. Residual mutation gene type in CR phase was most frequently detected in epigenetic regulator gene mutations, such as ASXL1, TET2, DNMT3A and IDH1/IDH2. Statistical analysis showed that the 2-year cumulative recurrence rate (CIR) in the molecular MRD positive group was higher than that in the molecular MRD negative group (86.8% vs. 51.3%; χ2 = 9.249, P = 0.002); the 2-year relapse-free survival (RFS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (13.2% vs. 48.7%; χ2 = 9.249, P = 0.002); the 2-year overall survival (OS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (58.0% vs. 100%; χ2 = 4.122, P = 0.042). Up to follow-up date, 3 patients with molecular MRD positive and 1 patient with molecular MRD negative who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) were still in disease-free survival. The results of monitoring MRD showed high consistency (76.7%, 33/43) in NGS and MFC. Compared with the other groups, the patients with both positive NGS and MFC had a higher relapse rate, and the difference was statistically significantly (P < 0.05).
Conclusions:Molecular MRD of AML patients is detected by using NGS technology, which could be used to predict the relapse and survival, suggesting that molecular MRD may guide post-remission treatment regimens and the determination of allo-HSCT indications.
