<p>Clinicopathological Characteristics and Mutational Profiling of Adult T-Cell Lymphoblastic Lymphoma in a Chinese Population</p>

Abstract

The purpose of this study is to perform a retrospective analysis of disease outcomes and mutational profiles in patients with adult T-cell lymphoblastic lymphoma (T-LBL). Patients and Methods: A total of 43 patients were treated over a 9-year period at a single institution. The study examined treatment outcomes, clinical characteristics, and the use of circulating tumor DNA (ctDNA) and mutational profiling for patient diagnosis. Results: The estimated overall survival (OS) and progression-free survival (PFS) time for all patients was 37.0 (95% CI: 17.7-56.2) and 28.1 (95% CI: 0.9-55.4) months, respectively. Chidamide maintenance was used in five patients exhibiting unfavorable genetic alterations, with no evidence of relapse. Next-generation sequencing of pretreatment tumor tissue was undertaken for 15 patients. NOTCH1 mutations were the most frequent genetic alterations, followed by mutations in PHF6, TP53, JAK1, JAK3, PTEN, and DNM2. The genetic profile of the blood was similar to that of the tumor. Kappa coefficient analysis (14 patients, 56 time points, kappa = 1.0, p = 0.00) indicated a 92.6% agreement between ctDNA response and tumor volume measurements at post treatment when compared with baseline. Detection of ctDNA predicted disease relapse in two patients. Conclusion: The prognosis of patients with adult T-LBL remains very poor. Detection of tumor-associated sequences in ctDNA may be an effective method for diagnosing T-LBL and measuring treatment efficacy. Incorporation of new drugs such as histone deacetylase inhibitors (HDACi)has the potential to improve outcomes in these patients.

Clinical Application of Liquid Biopsy in Non-Hodgkin Lymphoma

“…A number of studies have shown that the levels of cfDNA/ctDNA may be associated with poor clinical prognosis indicators, and at least two studies have reported that the levels of cfDNA/ctDNA were significantly associated with age, B symptoms ( 34 , 35 ), disease stage ( 34 , 35 , 59 , 66 ), and the International Prognostic Index (IPI) score ( 34 , 35 , 37 , 59 , 61 ) in DLBCL. In T cell lymphoblastic lymphoma, studies have confirmed that ctDNA concentrations are associated with IPI scores ( 64 ). These indicators are highly correlated with poor prognosis.…”

“…In a National Cancer Institute (NCI) study, the ctDNA of 17 patients with DLBCL who progressed after complete remission (CR) was analyzed, and 15 were found to be positive for ctDNA before progression was detected (95). Chen et al monitored the ctDNA of 14 T cell lymphoblastic lymphoma patients after treatment and found that in the 2 cases that relapsed during the maintenance phase, ctDNA could be detected before recurrence (64). The time from the detection of ctDNA to clinical recurrence was 83 and 84 days in these patients (64).…”

“…Chen et al monitored the ctDNA of 14 T cell lymphoblastic lymphoma patients after treatment and found that in the 2 cases that relapsed during the maintenance phase, ctDNA could be detected before recurrence (64). The time from the detection of ctDNA to clinical recurrence was 83 and 84 days in these patients (64). Shin et al followed up the ctDNA levels of NHL patients after treatment and found that 93% (13 of 14) of patients who achieved CR presented declining ctDNA, and ctDNA disappeared in most patients.…”

Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphoma

“…Hence, in this study, the previously reported lymphoma-related genes [ 19 ] overlapped with the WES data in the Cancer Genome Atlas (TCGA) database, plus hot spot mutation genes, 69 genes were obtained for developing a panel for TMB estimation (panel-TMB), which could be used for overall survival (OS) analysis. We further validated our findings using data from the TCGA database.…”

Clinical Value of ctDNA in Hematological Malignancies (Lymphomas, Multiple Myeloma, Myelodysplastic Syndrome, and Leukemia): A Meta-Analysis

“…Although many recent studies have focused on applications in hematological malignancies (8)(9)(10)(11)(12)(13), the results are still unclear. Therefore, we performed a meta-analysis to estimate the clinical application value in patients with hematological malignancies.…”