Hematology最新文献

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.

Background: Hemoglobin (Hb) Hekinan is a prevalent α-globin variant frequently missed in thalassemia screening centers using high-performance liquid chromatography (HPLC) or capillary electrophoresis. This study aims to investigate the hematological and molecular characteristics of Hb Hekinan in a large cohort.

Methods: Hb variants were identified using isoelectric focusing (IEF) and HPLC. Hb Hekinan was confirmed by direct DNA sequencing. Additional genetic determinants, including α-thalassemia, β-thalassemia and other variants, were detected using multiplex GAP-PCR, ARMS-PCR or direct DNA sequencing as appropriate.

Results: Among 61,997 Hb typing samples, 149 cases of Hb Hekinan were identified in Thai individuals and classified into 8 genotypic groups. These included 104 Hb Hekinan heterozygotes, 10 Hb Hekinan coexisting with α⁺-thalassemia, 3 Hb Hekinan with non-deletional α-variants, 6 Hb Hekinan with α⁰-thalassemia, 21 double heterozygote for Hb Hekinan and HbE, 3 Hb Hekinan with β-thalassemia trait, 1 triple heterozygotes (Hb Hekinan/α⁰-thalassemia/Hb E) and 1 quadruple heterozygote for Hb Hekinan/α⁺-thalassemia/Hb E/Hb Hope. Hb Hekinan was well-separated from Hb A using IEF but was frequently missed with HPLC. On HPLC, Hb Hekinan could only be identified when coexisting with α⁰-thalassemia. All cases presented with either normal Hb levels or mild anemia.

Conclusions: Hb Hekinan is a prevalent α-globin variant that is often undetected by HPLC but reliably identified using IEF. These findings highlight the importance of incorporating IEF for accurate diagnosis of Hb Hekinan. Most cases are clinically benign, even when interacting with other thalassemia syndromes or Hb variants.

Objective: To evaluate the short-term efficacy and safety of eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in China.

Method: Data were retrospectively collected from patients with PNH who received at least 3 months of full-dose eculizumab. Changes in clinical and laboratory indicators after 1, 3, and 6 months of eculizumab therapy and at the end of follow-up were documented. The incidence rates of breakthrough hemolysis (BTH), extravascular hemolysis (EVH), and adverse events were recorded.

Result: A total of 48 patients, including 27 males, with a median age of 46 (12-78) years were included. Twenty-four (50%) patients had classic PNH and 24 (50%) had bone marrow failure (BMF)/PNH. Eighteen (37.5%) patients required blood transfusion. The median duration of follow-up was 6 (3-15) months. During the follow-up period, Lactate Dehydrogenase (LDH) levels were lower than those at baseline (<0.05) at all observation points. The patients showed a significant reduction in creatinine levels from baseline (P = 0.022 and P = 0.039, respectively) at 1 and 3 months. At the end of the follow-up, fifteen (83.3%) became transfusion-independent. No new thrombotic events were observed. The FACIT-Fatigue score significantly improved (P < 0.05). No significant differences were observed in the changes in hemoglobin or LDH levels between patients with classic PNH and those with BMF/PNH. BTH was observed in 17.4% of patients and EVH in 10.4%. Mild adverse events occurred in 22.9% of patients. No deaths or clonal evolution was observed.

Conclusion: Eculizumab can effectively control the hemolytic symptoms of PNH with good tolerance for Chinese patients.

Objective: This study was designed to compare treatment patterns, clinical trial participation, and clinical outcomes among patients with small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL) or Mantle cell lymphoma (MCL) by site of care.

Methods: A nationwide electronic health record (EHR)-derived de-identified database was utilized for this study. Eligible patients were diagnosed with either CLL or MCL from 2013-2022 who received systemic therapy for their disease. Overall survival (OS) was analyzed using Kaplan Meier method, censoring patients without events at last observation in the database. Cox proportional hazards regression model was used to adjust for baseline covariates.

Results: A total of 6,372 patients with CLL and 3,411 with MCL met eligibility criteria for this analysis; 13.9% and 22.2%, respectively, were treated in academic settings. Academic settings were associated with higher patient volume and were more likely to treat MCL with CAR-T, enroll patients with CLL or MCL to clinical trials, and care for patients who were younger, White, and for CLL with higher rates of del(17p) mutations (all p < 0.01). Survival was significantly longer among patients treated in academic vs community settings (median OS not reached vs 80.5 months for CLL; 95.6 vs 68.7 months for MCL from start of first-line therapy).

Discussion: Patients who received care in academic settings differed from those treated in the community; care in academic settings was associated with significantly longer OS and higher trial participation. Further research is warranted to better understand the factors that may contribute to the observed outcomes.