Blood Research最新文献

Purpose: Given the notable increase in the incidence of multiple myeloma (MM) in Asia and advent of innovative treatments, this study aims to provide a comprehensive understanding of the treatment patterns, outcomes, and economic burden of MM across the lines of therapy (LOTs) in South Korea.

Methods: This retrospective cohort study was conducted using data from the National Health Insurance claims data provided by the Health Insurance Review and Assessment Database. An identification algorithm was developed to detect the regimens and LOTs. Treatment patterns and outcomes were assessed as real-world treatment sequence, treatment duration (rwTD), time to next-line treatment (rwTTNT), and overall survival (rwOS). Economic burden was assessed as healthcare resource utilization (HCRU) and the cost incurred per person per month.

Results: This study included 11,450 patients who were newly diagnosed with MM between January 2010 and December 2019. The observed real-world LOT patterns reflect the changes in South Korea's reimbursement scheme. Mean treatment-free intervals decreased from 11.59 months (SD 16.23) to 2.77 months (SD 6.14) from the first LOT (LOT 1) to LOT 5. Median rwTTNT decreased from 26.61 months (95% CI: 25.69-27.57) to 12.40 months (95% CI: 11.55-13.49), and median rwOS decreased from 61.88 months (95% CI: 59.11-65.46) to 13.65 months (95% CI: 11.88-16.22). The HCRU and associated costs increased substantially with the LOT advancement.

Conclusion: This large-scale observational study offers comprehensive insights into the real-world treatment of MM in South Korea. The study findings highlight the progressive nature of MM and increasing economic burden of advanced lines of treatment, underscoring the necessity for optimized treatment strategies.

Purpose: We used bioinformatics methods and Mendelian randomization (MR) analysis to investigate the hub genes involved in acute myeloid leukemia (AML) and their causal relationship with hemolysis, to explore a new direction for molecular biology research of AML.

Methods: We first differentially analyzed peripheral blood samples from 62 healthy volunteers and 65 patients with AML from the Gene Expression Omnibus database to obtain differentially expressed genes (DEGs), and intersected them with genes sourced from weighted gene co-expression network analysis (WGCNA) and the GeneCards database to obtain target genes. Target genes were screened using protein-protein interaction (PPI) network analysis and ROC curves to identify genes associated with AML. Finally, we analyzed the correlation between genes and immune cells and the relationship between toll-like receptor 4 (TLR4) and AML using MR.

Results: We compared peripheral blood expression profiles using an array of 62 healthy volunteers (GSE164191) and 65 patients with AML (GSE89565) (M0:25; M1:11; M2:10; M3:1; M4:7; M4 eo t [16;16] ou inv [16]:4; M5:6; M6:1) and obtained 7,339 DEGs (3,733 upregulated and 3,606 downregulated). We intersected these DEGs with 4,724 genes from WGCNA and 1,330 genes related to hemolysis that were identified in the GeneCards database to obtain 190 target genes. After further screening these genes using the PPI network, we identified TLR4, PTPRC, FCGR3B, STAT1, and APOE, which are closely associated with hemolysis in patients with AML. Finally, we found a causal relationship between TLR4 and AML occurrence using MR analysis (p < 0.05).

Conclusion: We constructed a WGCNA-based co-expression network and identified hemolysis-associated AML genes.

Purpose: Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differentiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare.

Methods: This retrospective chart review identified PBL cases that were treated at a single institute in southern Taiwan between 2008 and 2024.

Results: We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunophenotype, and three (33%) cases tested positive for Epstein-Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse.

Conclusion: In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.

Background: The clinical course of sickle cell anemia (SCA) is variable, with chronic hemolysis and end-organ damage caused by microvascular occlusion. We evaluated the efficacy and safety of thalidomide plus hydroxyurea (HU) compared with HU alone to determine whether the combination provides a superior clinical benefit and safety profile.

Methods: This was an open-label quasi-experimental clinical trial (Clinical Trials Registry of India, CTRI Registration Number 2023/04/065682). Patients with SCA aged > 12 years and postmenopausal females aged > 45 years were allocated 1:1 to receive either HU (20 mg/kg/day) and thalidomide (50 mg/day) in Group A or HU (20 mg/kg/day) only in Group B.

Results: The frequency of vaso-occlusive crises (VOCs), transfusion requirements, variations in hematological parameters (hemoglobin [Hb], fetal hemoglobin [HbF], and sickle hemoglobin [HbS]), and side effects between the groups were assessed over 12 months. Repeated-measures analysis of variance was used to determine changes across the observation period. The mean age of the 66 patients diagnosed with SCA (homozygous HbS mutation) was 32.9 (standard deviation ± 11.5) years, and 57.6% were males. Over the 12-month observation period, Group A had significantly fewer VOCs (3.48 ± 2.81) and packed red blood cell transfusions (3.61 ± 2.19) than Group B (11.36 ± 4.20 VOCs; 13.27 ± 3.70 transfusions) (p = 0.0001). There was a significant increase in Hb (8.2 ± 1.8 to 11.8 ± 1.2 g/dL), a decrease in HbS% (72.5 ± 5.5 to 64.5 ± 5.4), and a rise in HbF% (18.9 ± 5.1 to 28.4 ± 5.6) (p < 0.0001) in Group A.

Conclusion: Combining thalidomide with HU significantly reduced VOCs and transfusion requirements, improved Hb and HbF%, and decreased HbS levels.

Introduction: COVID-19 remains a major threat to immunocompromised individuals. The determination of circulating SARS-CoV-2 antibodies in patients at high risk for severe course of SARS-CoV-2 infection is important for estimating the vaccine-induced humoral immune response. Therefore, we assessed the status quo after winter to analyze the need for booster vaccinations.

Methods: Anti-spike IgG levels of 46 hospitalized patients with hematological and oncological diseases, measured between 21th December 2023 and 8th February 2024, were compared between subgroups of patients. Demographic data, underlying diseases, antineoplastic treatment, and the number of positive SARS-CoV-2 tests at the University Hospital Cologne were collected.

Results: Patients with different diseases showed varying SARS-CoV-2 spike antibody levels. The highest levels were found in patients with diffuse large cell B-cell lymphoma (DLBCL) and acute leukemia who had not received specific treatment or had just initiated treatment, whereas the lowest levels were found in patients with DLBCL, acute leukemia, and multiple myeloma who had received at least one line of treatment. The geometric mean antibody titers were higher in female patients than in male patients and were highest in patients aged 41-50 years while lowest in those aged 61-70 years.

Conclusion: The data presented confirm broad variations in SARS-CoV-2 anti-spike IgG levels across patients with different hematological and oncological diseases and highlight the complex interference of cancer biology, immune dysfunction, and treatment-related factors in shaping immune responses. Further research is needed to elucidate the mechanisms underlying these variations in antibody levels. We emphasize the need for regular booster vaccinations in this patient group.

Clonal hematopoiesis (CH), characterized by the expansion of hematopoietic stem and progenitor cells harboring somatic mutations, has emerged as a significant age-related phenomenon with profound implications for human health. While initially recognized in the 1960s, recent technological advances have revealed its complex nature and widespread prevalence, affecting up to 84% of individuals aged ≥ 70 years. The clinical significance of CH extends beyond its well-established role as a precursor to hematological malignancies, encompassing its association with cardiovascular diseases, chronic kidney disease, and other non-malignant disorders. This comprehensive review synthesizes the current understanding of CH, focusing on recent advances in genetic and molecular mechanisms, particularly the roles of commonly mutated genes such as DNMT3A, TET2, and ASXL1. We address the emerging distinction between myeloid and lymphoid CH, their differential impacts on disease progression, and the complex interplay between CH and inflammation. Special attention is given to newly identified genetic determinants of clonal expansion rates and their implications for disease progression. The review also examines the revolutionary concept of passenger-approximated clonal expansion rate and its utility in understanding CH dynamics. Furthermore, we discuss therapeutic strategies targeting inflammatory pathways and their potential in mitigating CH-associated complications. By integrating recent findings from genetic, molecular, and clinical studies, this review provides a framework for understanding CH as a systemic condition and highlights promising directions for therapeutic interventions.