Abstract
BackgroundAdult T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignant tumor with poor prognosis. However, accurate prognostic stratification factors are still unclear.MethodsData 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.ResultsForty-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.ConclusionsOur risk stratification models exhibited good prognostic roles in adult T-ALL/LBL patients and might guide individualized treatment and ultimately improve their outcomes.
Highlights
T-cell acute lymphoblastic leukemia (T-ALL) in adults is an aggressive and heterogeneous hematopoietic malignancy caused by the clonal proliferation and abnormal differentiation of T lymphoid progenitor cells
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 hematopoietic stem cell transplantation (HSCT) were integrated into a risk stratification model of overall survival (OS)
complete remission (CR), minimal residual disease (MRD), event-free survival (EFS), relapse-free survival (RFS), and OS were calculated by the Kaplan–Meier method, and differences between groups were compared by the logrank test
Summary
T-cell acute lymphoblastic leukemia (T-ALL) in adults is an aggressive and heterogeneous hematopoietic malignancy caused by the clonal proliferation and abnormal differentiation of T lymphoid progenitor cells. The intensity of T-ALL treatment is based on the risk stratification using a combination of age, white blood cell (WBC) count, and extramedullary infiltration, cytogenetic, and early response to induction chemotherapy. It is still difficult to accurately predict the prognosis of adult T-ALL patients according to present risk stratification models. A recent study revealed that the genomic analyses can early predict the relapse of adult T-ALL driven by mutated genes and may guide clinical decisions [15]. Up-to-date risk stratification of TALL patients based on the genome analyses showed that gene mutations had impacts on prognosis and were conducive to subdivide cases into different risk groups [17]. Integration of gene mutations into current risk stratification criteria may be beneficial to improve prognosis identification and therapeutic efficacy.
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