Prognostic Significance of Comprehensive Gene Mutations and Clinical Characteristics in Adult T-Cell Acute Lymphoblastic Leukemia Based on Next-Generation Sequencing

BACKGROUND: Adult T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignant tumor with poor prognosis. However, accurate prognostic stratification factors are still unclear. METHODS: Data from 90 adult T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients were collected. The association of gene mutations detected by next-generation sequencing and clinical characteristics with the outcomes of T-ALL/LBL patients were retrospectively analyzed to build three novel risk stratification models through Cox proportional hazards model. RESULTS: Forty-seven mutated genes were identified. Here, 73.3% of patients had at least one mutation, and 36.7% had ≥3 mutations. The genes with higher mutation frequency were NOTCH1, FBXW7, and DNMT3A. The most frequently altered signaling pathways were NOTCH pathway, transcriptional regulation pathway, and DNA methylation pathway. Age (45 years old), platelet (PLT) (50 G/L), actate dehydrogenase (LDH) (600 U/L), response in D19-BMR detection, TP53 and cell cycle signaling pathway alterations, and hematopoietic stem cell transplantation (HSCT) were integrated into a risk stratification model of event-free survival (EFS). Age (45 years old), white blood cell (WBC) count (30 G/L), response in D19-BMR detection, TP53 and cell cycle signaling pathway alterations, and HSCT were integrated into a risk stratification model of overall survival (OS). According to our risk stratification models, the 1-year EFS and OS rates in the low-risk group were significantly higher than those in the high-risk group. CONCLUSIONS: Our risk stratification models exhibited good prognostic roles in adult T-ALL/LBL patients and might guide individualized treatment and ultimately improve their outcomes.