Clinical outcomes based on molecular risk stratification using next-generation sequencing in adult filipino patients with AML at a tertiary hospital
Introduction/Background/Significance: Acute myeloid leukemia (AML) is a common hematologic malignancy found in adults characterized by a range of genetic abnormalities. Next-generation sequencing (NGS) has demonstrated efficacy in revealing the diversity of these genetic mutations, facilitating risk classification and developing targeted treatments. However, the utilization of NGS has been limited due to its high cost and limited availability.
Materials and Methods/Case Presentation/Objective: This study aims to evaluate the association between genetic risk stratification using NGS and clinical outcomes, including 3-year overall survival, among Filipino AML patients at a tertiary hospital.
Methods: This retro-prospective cohort pilot study included all newly diagnosed AML patients aged 18 years or older from 2018 to 2021. Chart review was done to retrieve information regarding clinical characteristics of patients. Patients/ relatives were contacted, with consents secured, for follow-up inquiring current status of patients. NGS was performed on samples with a DNA concentration of at least 10ng/uL. Patients who had prior treatment or other malignancies and incomplete charts were excluded. Clinical profiles were analyzed using descriptive statistics. The association between risk stratification and treatment response along with 3-year overall survival was assessed using univariate and multivariate statistics, including Chi-square tests, logistic regression, and multiple logistic regression.
Results/Description/Main Outcome Measures: Among 24 patients, 87.5% were classified as poor risk (PR) with a median overall survival of 11 months, while 12.5% were deemed favorable (FR) with a median overall survival of 3 months. In the poor risk group (n=21), the majority were male (57.1%) and exhibited blasts (81%), with 63.2% showing complete response to treatment and an 85.7% mortality rate. Similarly, in the favorable risk group, males comprised 66.7% of patients, with blasts present in 66.7%. However, no response to treatment was recorded since they were unable to undergo treatment for a sufficient duration to ascertain their treatment response, resulting in a 100% mortality rate (died of subarachnoid hemorrhage, cardiac arrest, and unknown cause). Age at diagnosis (PR= 45 vs FR= 76; p=0.002), neutrophil count (PR= 18.81 vs FR= 48.67; p=0.029), and number of mutated genes (PR= 3.57 vs FR= 0.33;p=0.029) were statistically significant. The most common mutation identified was TET2. Most patients in the poor risk group received standard treatment of cytarabine for 7 days with an anthracycline for 3 days (66.7%), while those in the favorable risk group received other therapies (100%). All 3 patients who had favorable risk stratification were more than 70 years old and received Decitabine, with 1 patient given additional Venetoclax treatment.
The main limitation of our study is the small sample size which may limit the generalizability of the findings.
Conclusions: Through comprehensive genetic profiling, NGS revealed significant heterogeneity in genetic mutations among AML patients, enabling personalized risk categorization upon diagnosis. Survival outcomes differed significantly between risk groups, with median survival durations reflecting the impact of genetic risk stratification on patient prognosis. Despite challenges related to cost, integrating NGS testing into routine diagnostic protocols can enhance risk assessment and optimize personalized treatment strategies, ultimately improving patient survival in resource-limited settings.
