Search

Objective To investigate the correlation between gene mutations and clinical features, prognosis, and the risk of acute myeloid leukemia (AML) transformation in patients with myelodysplastic syndrome (MDS). Methods We retrospectively analyzed clinical data from 100 MDS patients and next-generation sequencing（NGS） was employed to identify 34 MDS-associated gene mutations across all patients. The mutation rates and distributions were analyzed to assess the correlation of high-frequency mutations (≥10%) with clinical features, prognosis, and the risk of AML progression. Results NGS identified 32 types of gene mutations across the cohort, with 84% of patients harboring at least one mutation. Mutations were most frequently observed in the MDS-MLD subtypes (39.3%) and predominantly in patients aged ≥60 years（82.8%，53/64）. The ASXL1 gene exhibited the highest mutation ratio (26%), with TET2, U2AF1, DNMT3A, RUNX1, TP53, and SF3B1 also showing incidence higher than 10%. ASXL1 frequently co-mutated with RUNX1 and with TP53 exclusion. It revealed that higher percentages of bone marrow blasts were seen in ASXL1-positive patients, lower platelet counts in U2AF1-positive patients, and a greater prevalence of DNMT3A mutations in elderly patients (85.7%). RUNX1 mutations were associated with elevated white blood cell counts, while TP53 mutations correlated with higher IPSS-R scores（6 vs 4.5）(P=0.016 )and elevated LDH levels（P=0.002）（420 U/L vs 222 U/L）, respectively. The median follow-up period was 18.6 months, and the median overall survival was 27.1 months, with TP53 mutations being an independent predictor for poor overall survival (OS). During follow-up, 15% of patients progressed to AML, with DNMT3A mutations identified as an independent risk factor for AML transformation（HR=3.73）. Conclusions Genetic mutations are prevalent in MDS and correlate with distinct clinical features. In this cohort of MDS patients, the mutation rate of MDS-related genes is 84%. TP53 mutations were associated with poor prognosis, whereas DNMT3A mutations are linked to an increased risk of AML transformation.

We explored the frequency of CD14−CD10−CD45+HLA‐DR−SSC++ neutrophils (CD10− neutrophils) in patients with non‐Hodgkin's lymphoma (NHL), and their immunologic characteristics and clinical significance. Patients with NHL who were newly diagnosed (NDP; n = 33), in remission (RMP; n = 28) and relapsed (RLP; n = 29) were included, and 47 volunteers were recruited as healthy controls (HCs). The frequency of CD10− neutrophils in the peripheral blood from HC and patients with NHL was detected. CD10− and CD10+ neutrophils were sorted, and their cytology was analyzed. CD3+ T cells were also isolated and cultured with the autologous CD10− or CD10+ neutrophils, after which the proliferation and death rates of T cells were determined. The levels of arginase‐1 (Arg‐1) and reactive oxygen species (ROS) in CD10+ or CD10− neutrophils were examined. Few CD10− neutrophils were detected in HCs but were significantly elevated in patients with NHL, especially in NDP and RLP. In addition, CD10− neutrophils in NDP with advanced stage and high risk were markedly higher than those in NDP with limited stage and low risk. In RMP and RLP, the relapse‐free survival and overall survival in patients with high CD10− neutrophils were shorter than those with low CD10− neutrophils. CD10− neutrophils from patients with NHL, which mainly consist of immature neutrophils, inhibit T‐cell proliferation and facilitate T‐cell death. Furthermore, a significant increase was observed in Arg‐1 expression, along with an increase to a certain extent in ROS. CD10− neutrophils in patients with NHL have characteristics of myeloid‐derived suppressor cells and may be related to disease progression and poor prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Chimeric antigen receptor T (CAR-T) cell therapy is an effective bridging treatment for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in relapsed or refractory acute lymphoblastic leukemia (ALL). However, repetitive CAR-T cell therapy and allo-HSCT can only be performed in a few patients because of technical difficulties and patients' physical, economic, and social conditions. Case Presentation: A 23-year-old female patient with second relapsed B-cell ALL (B-ALL) underwent human-murine chimeric CD19 CAR-T cell therapy twice, human-murine chimeric CD22 CAR-T cell therapy once, and humanized CD19 CAR-T cell therapy once. Moreover, she was sequentially bridged to her mother donor allo-HSCT once and cousin donor allo-HSCT once. Conclusion: Repetitive CAR-T cell therapy bridging to repetitive allo-HSCT is still a safe and active therapeutic strategy for patients with relapsed or refractory ALL. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the expression pattern of Wilms tumor 1 (WT1) gene at diagnosis, complete remission (CR) and relapse status in non-acute promyelocytic leukemia (non-APL) acute myeloid leukemia (AML) patients, and further explore the prognostic value of measurable residual disease (MRD) assessment by WT1 gene and multiparameter flow cytometry (MFC). Our results showed that the average expression level of WT1 was 4026 ± 616.1 copies/104 ABL at diagnosis, 155.3 ± 36.03 copies/104 ABL at CR, and 1766 ± 238.8 copies/104 ABL at relapse, with statistically significant differences (p =.000). ROC analysis showed that WT1 expression levels were 118.1 copies/104 ABL and MFC-MRD was 0.155%, which had good predictive efficacy for relapse of patients during consolidation therapy. Both WT1-MRD and MFC-MRD had a significant impact on relapse-free survival (RFS) and overall survival (OS). Patients with WT1-MRD positive or MFC-MRD positive were associated with worse RFS (HR 3.840, 95% CI 1.582–9.320, p =.003), (HR 4.464, 95% CI 1.841–10.984, p =.001) and worse OS (HR 2.963, 95% CI 1.058–8.295, p =.039), (HR 3.590, 95% CI 1.254–10.280, p =.017). Besides, compared with patients who were negative for both WT1-MRD and MFC-MRD, patients who were positive both WT1-MRD and MFC-MRD were associated with worse RFS (HR 6.200, 95% CI 2.206–17.430, p =.001) and worse OS (HR 4.886, 95% CI 1.388–17.197, p =.013). This study demonstrates that combined assessment of MRD by WT1 and MFC improves relapse and prognosis prediction in non-APL AML patients, and may help guide interventions for disease relapse. [ABSTRACT FROM AUTHOR]