The prognostic impact of reduced variant burden in elderly patients with acute myeloid leukemia treated with decitabine

The prognosis of elderly patients with AML is poor with various causes including patient's medical comorbidity, performance status and disease biology. Even though genomic advance has improved the development of next-generation sequencing (NGS), it is unclear which genetic mutations are associated to identify the prognosis of elderly AML patients. Therefore, we evaluated the prognostic impact of genetic mutation and the role of NGS based MRD monitoring in 123 elderly patients diagnosed with AML who received HMAs treatment. Through the genetic profiling including the targeted deep sequencing of 51 genes, TP53, TET2 gene mutation and complex karyotype at diagnosis showed significantly poor prognosis in this study. Overall response rate was 35.1% and there was no difference in overall response rate by ELN risk stratification, cytogenetic abnormality, genetic mutation. We analyzed the VAF dynamics of 49 patients in follow up BM samples after 4th cycle of decitabine, and the optimal cut off value was ?53.3%. The survival outcome of patients who showed more than ?53.3% reduction of initial VAF after 4th cycle of decitabine was significantly better than other group(Median OS of group with reduced VAF (?VAF = 53.3%, n=24), 20.5 month; group with stable VAF (?VAF <53.3%, n=20), 9.8 month; no mutated group (n=11), 10.9 month; not available of follow up targeted NGS analysis (n=29), 6.2 month; p < 0.001). In conclusion, ?VAF as the early predictors of responsiveness to decitabine mono therapy would be helpful to decide whether to continue treatment or combine novel agents.