Hematology最新文献

Objectives: Acquired aplastic anemia (AA) is a bone marrow failure syndrome whose pathogenesis remains incompletely understood. This study aimed to explore the genetic determinants underlying AA and identify potential therapeutic targets.

Methods: We integrated summary data - based Mendelian randomization (SMR) and colocalization analysis to identify genes causally linked to AA. Key candidates were validated using single-cell RNA sequencing to assess their expression and pseudotime dynamics. We explored B-cell - mediated cell communication related to immunosuppressive therapy response. Serum expression of candidate genes was validated and correlated with clinical outcomes.

Results: SMR analysis identified 28 genes significantly associated with AA, among which NFKB1 emerged as a central regulatory factor. scRNA-seq data confirmed NFKB1's differential expression in B cells and its dynamic regulation during disease progression. Discussion and conclusion: This study is the first to comprehensively characterize the role of NFKB1 in the pathogenesis of AA through integrated multi-omics analysis and providing novel insights for the development of targeted interventions.

Objectives: To explore the differences between primary immune thrombocytopenia (ITP) and ITP secondary to connective tissue disease (CTD-ITP).

Methods: A retrospective observational study was conducted on patients newly diagnosed with primary ITP and CTD-ITP hospitalized in the Hematology Department of Tianjin Medical University General Hospital from July 1, 2019 to December 31, 2023. Data, including demographic details, medical history records, and laboratory test results, were collected, followed by a comparative analysis to identify differences between the groups.

Results: Compared with patients in the primary ITP group, those in the CTD-ITP group exhibited a female predominance, along with lower platelet and hemoglobin levels. Total globulin and immunoglobulin G (IgG) concentrations were higher in the CTD-ITP group than in the primary ITP group, whereas albumin, complement C3, and C4 levels were lower. Antinuclear antibody titers were higher in the CTD-ITP group, and the percentages of regulatory B (Breg) cells and transitional B cells were lower. A greater percentage of abnormal megakaryocytes was observed in the CTD-ITP group. Furthermore, a larger proportion of patients in the CTD-ITP group met treatment criteria, necessitated more intensive therapy, and required a longer duration to achieve complete remission.

Conclusion: Compared with patients in the primary ITP group, those in the CTD-ITP group had more severe conditions, more intense immune disturbances, and greater treatment challenges. Individualized treatment is needed.

Objective: Venous thromboembolism (VTE) is a significant global health concern. Recent investigations indicate that anemia may increase the risk of VTE. Nevertheless, the presence of confounding variables in observational studies has rendered the causal association between anemia and VTE inconclusive.

Methods: This study utilized a two-sample Mendelian Randomization methodology, employing genetic variants derived from specific large-scale genome-wide association studies as instrumental variables to investigate the causal relationship between anemia and VTE. Rigorous statistical analyses were conducted, including the primary analysis based on the inverse-variance weighted (IVW) method, along with supplementary analyses such as MR-Egger, weighted median, and MR-PRESSO, to ensure the reliability and validity of our results.

Results: Our analysis suggests a potential causal association between anemia and certain thrombotic events. Anemia was associated with an increased risk of thrombosis and embolism in unusual sites (OR = 1.446, 95% CI: 1.104-1.895, p = 0.007), while aplastic anemia showed a weak positive association with overall VTE risk (OR = 1.065, 95% CI: 1.003-1.131, p = 0.040).

Conclusions: Anemia individuals face an increased risk of embolism and thrombosis events, and AA exhibits a potential association with VTE. Nevertheless, a comprehensive comprehension of the precise underlying mechanisms linking anemia/AA and VTE necessitates further exploration through supplementary research.

Objective: Acute myeloid leukemia (AML) exhibits significant heterogeneity and aggressiveness. This study aimed to investigate T cell heterogeneity in the AML tumor microenvironment using single-cell RNA sequencing (scRNA-seq) and identify potential biomarkers for prognosis and precision therapy.

Methods: scRNA-seq data from AML patient samples were analyzed to identify T cell subsets. A prognostic risk model was constructed using random forest and LASSO regression analyses based on key genes derived from a specific T cell cluster (Cluster 4). The model's predictive performance was validated using external datasets.

Results: Analysis revealed significant functional heterogeneity among T cell subsets. Cluster 4 T cells showed distinct gene set activities related to immune regulation. Three genes - BSG, PPARD, and SLC16A8 - were identified as independent prognostic factors. The risk model effectively stratified patients into high-risk and low-risk groups, with the high-risk group demonstrating significantly poorer survival outcomes. The model showed robust predictive accuracy, with areas under the ROC curve of 0.78, 0.86, and 0.86 for 1-, 3-, and 5-year survival, respectively.

Conclusion: This study highlights the functional diversity of T cells in AML and identifies BSG, PPARD, and SLC16A8 as promising biomarkers for prognostic stratification. The developed risk model provides a valuable tool for guiding personalized treatment strategies in AML.

Introduction: Patients with immune thrombocytopenic purpura (ITP) usually express thyroid antigen-specific antibodies. The purpose of this study was to explore the causal relationship between Hashimoto's thyroiditis (HT) and ITP.

Methods: A two-sample Mendelian randomization (TSMR) analysis was applied to investigate the potential causal relationship between HT and ITP in European population. Five complementary methods including inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), weighted median, and weighted mode were performed in our study. Risk genes of HT and ITP were selected through Mendelian randomization (MR), and the common risk genes were further analysed by bioinformatics methods to explore the common pathogenesis of the two diseases.

Results: The MR analysis revealed a potential causal relationship between HT and risk of ITP [odds ratio (OR) = 1.22; 95% confidence interval (CI) 1.01, 1.49; P = 0.046]. Gene eQTL data were obtained from the IEU database. HT and ITP were respectively treated as outcome variables for MR analysis, and a total of 32 common risk genes were selected, including 12 high-risk genes and 20 low-risk genes. Functional analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis revealed that risk genes were closely related to antigen processing and presentation, and played a crucial role in the process of various viral and bacterial infections.

Conclusion: Our study demonstrated that HT may increase the risk of ITP, and revealed the role of their common risk genes in the development of the two diseases.

Background: Progressive multifocal leukoencephalopathy (PML) is characterized by demyelination in the central nervous system. It is caused by infection with human polyomavirus 2 and has a poor prognosis. Therapeutic strategies involve restoring immune function and/or discontinuing immunosuppressive treatment. Immune checkpoint inhibitors such as those targeting programmed death receptor-1 (PD-1) can alleviate PML by restoring T cell function. There are no case reports on the use of the PD-1 inhibitor, Sintilimab, for treating PML. Here, we report a case of successful treatment of PML with sintilimab following allogeneic hematopoietic stem cell transplantation.

Case presentation: A 35-year-old woman with high-risk acute myeloid leukemia underwent allogeneic hematopoietic stem cell transplantation after induced remission and developed PML 12 months after transplantation. She received five courses of 100 mg every 4 weeks with monitoring by magnetic resonance imaging (MRI) and viral load in the cerebrospinal fluid, showing clinical improvement, resolution of neurological symptoms, and reduced viral load. MRI showed initial exacerbation of lesions but significant improvement after five courses of treatment. No graft-versus-host disease occurred, but manageable immune reconstitution inflammatory syndrome was observed.

Conclusion: Sintilimab, a PD-1 inhibitor, might be used to treat PML in patients with hematologic malignancies undergoing allo-HSCT, which needs further investigation.

Objective: This review aimed to examine if there is any difference in the risk of thrombosis and central line-associated bloodstream infection (CLABSI) with the use of peripherally inserted central catheter (PICC) and conventional central venous catheters (CVC) in hematological cancer patients.

Methods: We searched the online databases of PubMed, CENTRAL, Scopus, Web of Science, and Embase for all types of studies comparing the risk of thrombosis and CLABSI between PICC and CVC. The search ended on 23rd September 2024.

Results: Eight studies were included. One was a randomized trial while others were observational studies. Meta-analysis showed no statistically significant difference in the risk of thrombosis between PICC and CVC (OR: 1.69 95% CI: 0.75, 3.82 I²= 78%). However, these results were not stable on sensitivity analysis. The exclusion of two studies indicated a higher risk of thrombosis with PICC. Pooled analysis showed that the risk of CLABSI was significantly lower with PICC as compared to CVC (OR: 0.52 95% CI: 0.40, 0.66 I²= 0%). Results of subgroup analysis based on study design and diagnosis showed conflicting results.

Conclusions: There is conflicting evidence on the risk of thrombosis between PICC and CVC when used for hematological cancer patients. There could be a tendency of higher risk of thrombosis with PICC which needs to be confirmed by further studies. However, the use of PICC may reduce the risk of CLABSI in such patients. The quality of evidence is low owing to the predominance of observational studies with high inter-study heterogeneity.

Background: Acute lymphoid leukaemia (ALL) is a significant cause of morbidity and mortality globally, with increasing incidence rates observed in Saudi Arabia. Despite advances in treatment, there is a lack of localized, sex-specific forecasts to guide public health interventions.

Objective: This study aims to forecast the future incidence of acute lymphoid leukaemia in males and females using ARIMA models.

Methods: Saudi national cancer registries data from 1990 to 2019 were used. The dataset was divided into training (80%) and testing (20%) sets. ARIMA models were developed for male and female incidence, with model parameters determined using ACF and PACF plots. Stationarity was assessed using the Augmented Dickey-Fuller test, and model accuracy was validated using MAE, MSE, and MAPE. Forecasts included point estimates and 95% confidence intervals.

Results: For males, the ARIMA (3, 3, 3) model forecasted an increase in ALL incidences from 957 cases in 2020 to 2181 cases in 2029. For females, the ARIMA (4, 3, 0) model projected an increase from 1019 cases in 2020 to 2159 cases in 2029. The models demonstrated high accuracy, with MAE of 1.19895 and 2.749188, MSE of 62.33 and 31.83, and MAPE of 0.6805807 and 1.443453 for males and females, respectively.

Conclusion: Forecasts indicate a substantial rise in ALL incidence among both sexes, highlighting the urgent need for improved surveillance, early detection, and healthcare capacity planning. Incorporating ARIMA modelling into routine monitoring could support proactive resource allocation. Further studies should integrate additional predictive variables to enhance model precision.

Background: Despite recent advances, factor replacement therapy remains a cornerstone in hemophilia A treatment. Efmoroctocog alfa, a recombinant FVIII Fc fusion protein (rFVIIIFc), has an extended half-life allowing higher FVIII levels and less frequent dosing than standard half-life (SHL) products, without increasing factor consumption.

Methods: A-SURE was a 24-month prospective, non-interventional study assessing real-world effectiveness of rFVIIIFc prophylaxis. This post-hoc, intra-patient analysis included patients with hemophilia A (PwHA) who switched from SHL FVIII to rFVIIIFc prophylaxis. Effectiveness endpoints included annualised bleeding rate (ABR), annualised joint bleeding rate (AjBR), weekly injection frequency and weekly factor consumption.

Results: Of 131 PwHA eligible for analysis, mean ABR and AjBR decreased from 3.7 and 2.4 to 1.8 and 1.1, respectively, after switching (mean [95% confidence interval (CI)] change of -1.9 [-3.0, -0.8] and -1.2 [-2.0, -0.5]). Mean weekly injection frequency decreased from 3.1 to 2.3 (mean [95% CI] change of -0.8 [-1.0, -0.7]); weekly factor consumption reduced from 89.7 to 84.1 international units (IU)/kg, respectively (mean [95% CI] change of -5.7 [-10.7, -0.6]). These trends were consistent across age groups.

Conclusion: This intra-patient comparison demonstrates switching from SHL FVIII to rFVIIIFc prophylaxis reduces frequency of bleeds, injection frequency, and factor consumption, complementing previously reported data from A-SURE.Trial registration:ClinicalTrials.gov identifier: NCT02976753.

Background: Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with FLT3-Internal Tandem Duplication (ITD) mutation have a poor prognosis and high risk of relapse, even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Prevention of disease relapse remains a challenge.Objective: To investigate the efficacy and tolerability of gilteritinib maintenance therapy in R/R AML patients with FLT3-ITD mutation.Methods: We retrospectively analyzed 96 AML patients who received allo-HSCT between 2017 and 2022. Patients were divided into two groups based on whether they received gilteritinib maintenance therapy or not. To minimize selection bias, we implemented propensity score matching and selected 80 propensity score-matched patients for comparison, 40 in each group. The therapeutic process and clinical outcomes were retrospectively analyzed.Results: All patient baseline and transplant characteristics were similar between the gilteritinib and the control group. Gilteritinib therapy conferred significant survival advantages (P = 0.013 for OS and P = 0.026 for RFS). Relapse remained the main reason of treatment failure with 3-year incidence of 25.0% (95%CI 12.8-39.2%) and 55.0% (95%CI 38.1-69.0%) for the gilteritinib group and the control group(P = 0.010). In multivariate Cox regression analysis, gilteritinib maintenance was the only factor associated with improved OS (HR = 0.395, P = 0.040) and RFS (HR = 0.447, P = 0.030).Conclusions: Our results indicated that gilteritinib maintenance therapy reduced the risk of relapse for FLT3-ITD mutated R/R AML. Compared with patients without maintenance therapy, gilteritinib treatment showed a similar incidence of NRM and GVHD, leading to significant survival advantages in this high-risk cohort of patients.