Genetic Mutations and Their Clinical Implications in Older Patients with Acute Myeloid Leukemia

Objective?A number of leukemia-associated and patient-specific factors are related to the prognosis in older acute myeloid leukemia (AML) patients. In this study, we focus on the genetic mutations of older patients with AML and their impact on the clinical and prognosis. Methods: We retrospectively analysed the clinical, cytogenetic and laboratory data of 427 de novo non-M3 AML patients treated in our hospital from January 2000 to March 2014. We compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Then clinical curative effect survival rate of patients in two groups was observed after followed-up. Results: Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently had one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetic into three risk groups. Conclusion: Older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetic and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment.