Abstract
Several molecular aberrations affect the prognosis of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with excess blasts (EB). This study aimed to determine the incidence and clinical impact of molecular genetic aberrations in Thai patients with AML and MDS-EB, detected by the next-generation sequencing (NGS) technique. This prospective, observational study was conducted between 2018 and 2020 on newly diagnosed Thai AML or MDS-EB patients aged above 15 years. NGS was performed using a custom amplicon-based targeted enrichment assay for 42 genes recurrently mutated in myeloid neoplasms. The molecular results were correlated with baseline patient and disease characteristics as well as outcomes. Forty-nine patients were enrolled in this study. The median age was 56 years (interquartile range [IQR], 44–64), with nearly equal proportions of males and females. The median number of mutations was 3 (IQR, 2–4). The most frequent alterations were FLT3 internal tandem duplications (ITD) (28.6%), DNMT3A (24.5%), and WT1 (22.4%) mutations. FLT3-ITD was more frequent in the de novo AML group than in the MDS/secondary AML group, whereas in the MDS/secondary AML group, ASXL1, ETV6, and SRSF2 mutations were more frequent. Patients aged greater than 65 years and patients with mutated TP53 were more likely to have inferior overall survival from multivariate analysis. FLT3-ITD was the most common mutation among newly diagnosed Thai AML patients. TP53 mutation and advanced age were independent adverse factors for survival outcome. The genetic landscapes of AML patients vary between national populations. Thai Clinical Trials Registry identifier: TCTR20190227003.
Highlights
Two main standard recommendations for acute myeloid leukemia (AML), published by the European LeukemiaNet (ELN) and the National Comprehensive Cancer Network, are being used to determine patients’ riskIn addition, personalized treatment is widely integrated with AML treatment strategies, depending on mutational status; for example, the FLT3 inhibitor midostaurin combinedAnn Hematol (2021) 100:1983–1993 with intensive induction and consolidation chemotherapy followed by a 1-year maintenance therapy yielded significantly better survival outcomes of patients with FLT3-mutated AML [7, 8]
Health-care institutes, especially those in developed countries, are increasingly adopting the next-generation sequencing (NGS) method to investigate the mutational status of newly diagnosed AML and myelodysplastic syndrome (MDS)-excess blasts (EB) patients
The inclusion criteria were as follows: (1) patients aged above 15 years; (2) patients with de novo AML, secondary AML, or MDS-EB; and (3) patients requiring treatment and follow-up at Siriraj Hospital, Thailand
Summary
Ann Hematol (2021) 100:1983–1993 with intensive induction and consolidation chemotherapy followed by a 1-year maintenance therapy yielded significantly better survival outcomes of patients with FLT3-mutated AML [7, 8]. A comprehensive genetic investigation of MDSEB patients is required, just as for patients with AML. The main limitation of this technique is that each mutation has to be evaluated separately, which is time-consuming. This is in particular clinically relevant for patients with newly diagnosed AML and MDS-EB. Health-care institutes, especially those in developed countries, are increasingly adopting the NGS method to investigate the mutational status of newly diagnosed AML and MDS-EB patients. Comprehensive genetic profiles for the Southeast Asian population, including Thais, have not been fully studied
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