Publication Date:
2018-11-29
Description:
Introduction Acute myeloid leukemia (AML) is a highly heterogeneous disease with various genetic abnormalities. Cytogenetics, gene mutations, gene expression profiles, and microRNA expressions affect prognosis in AML patients. Some of these exams are cumbersome and not readily available. In contrast, routine complete blood counting and morphological classification is a simple and real time method, and may be used for prediction of response to treatment. Rapid peripheral blood (PB) blasts clearance after induction chemotherapy has been shown to predict prognosis in AML patients, but those studies recruited small cohorts or lacked molecular correlations. In this study, we aimed to not only investigate the prognostic significance of this method in a large cohort but also extend its implications to genetic and biological levels. Method A cohort of 333 de novo non-M3 AML patients who received standard chemotherapy at the National Taiwan University Hospital from 2003 to 2015 were included. The percentages of their PB blasts in the first week after initiation of induction chemotherapy were examined by morphological observation. Mutation analyses of 15 relevant molecular markers, including FLT3 (ITD and TKD), N-RAS, K-RAS, KIT, CEBPA, RUNX1, as well as NPM1, WT1, ASXL1, MLL/PTD, DNMT3A, IDH1, IDH2, and TET2, were performed in bone marrow mononuclear cells from 165 patients at diagnosis, who had available cryopreserved samples. We profiled whole-genome gene expression using Illumina HumanHT-12 v4 Expression BeadChip (Illumina, San Diego, CA) in 83 patients, who had enough mRNA for analyses. The difference in clinical features, cytogenetics, gene mutations, gene expression profiles, and treatment outcomes between patients who had PB blasts clearance within 7 days and those who failed were analyzed. Results Among the 333 patients, 154 (46.2%) patients achieved clearance of PB blasts within 7 days of starting induction chemotherapy. There was no difference in gender, age, and hemograms at diagnosis between the two groups. The patients failed to clear PB blasts within one week had higher incidence of FAB M0 (5.6% vs. 0.6%, p=0.012), higher percentage of 2017 European LeukemiaNet (ELN) adverse-risk category (40.8% vs. 26.0%, p=0.004), and lower incidence of mutated NPM1 (10.6% vs. 22.5%, p=0.039), FLT3-ITD (11.8% vs. 26.6%, p=0.015), and biallelic mutated CEBPA (9.8% vs. 24.1%, p=0.015) than those who cleared the PB blasts in 7 days. Failure to clear PB blasts within 7 days was a significant unfavorable risk factor for overall survival (OS) [5-year survival rate 53.3% vs. 76.0%, p=0.004 (figure 1)], and relapse-free survival (RFS) [median RFS 6.6 months vs. 18.6 month, p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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