Blood Research最新文献

Cell-based artificial platelet production has made remarkable progress over the past three decades, driven by the need for safe and stable platelet sources in the face of donor limitations and transfusion-related risks. This review provides a chronological overview of the evolution of in vitro platelet production from various cell sources (CD34+ hematopoietic stem cells, embryonic stem cells, induced pluripotent stem cells (iPSCs), and others) and highlights key advances in the field. We outline developments from the foundational experiments of the 1990s, through the introduction of iPSCs in the mid-2000s, to the adoption of three-dimensional culture and bioreactor technologies in the late 2010s and the emergence of clinical trials in the 2020s. In addition, we discuss future perspectives, including the role of advanced gene editing and scalable biomanufacturing technologies in accelerating clinical translation. This comprehensive review underscores the promise of artificial platelet production technologies for clinical applications and discusses the remaining challenges, such as scalability, cost-effectiveness, and regulatory hurdles. The recent completion of the first human clinical trials using iPSC-derived platelets marks a significant milestone, pointing to a future in which patient-specific or human leukocyte antigen-universal platelets may be transformed into transfusion medicine and regenerative therapies.

Purpose: Neutropenia is a hematologic condition characterized by an absolute neutrophil count < 1500/μL, associated with increased infection risk. This review aimed to provide an updated overview of the classification, pathophysiology, etiology, diagnosis, and management of neutropenia in congenital and acquired forms.

Methods: We conducted a comprehensive literature review of various causes of neutropenia, including genetic syndromes, autoimmune disorders, infections, and drug-induced mechanisms. Emphasis was placed on clinical manifestations, underlying mechanisms, diagnostic algorithms, and therapeutic approaches, including recent advances in molecular diagnostics and biologic therapies.

Results: Neutropenia can result from decreased neutrophil production, immune-mediated destruction, or abnormal distribution. Congenital neutropenia is often linked to mutations in genes such as ELANE, HAX1, and SBDS. Acquired neutropenia can be caused by chemotherapy, infections, autoimmune diseases, or nutritional deficiencies. Diagnostic evaluation requires a stepwise approach incorporating clinical history, blood counts, peripheral smear, bone marrow biopsy, and molecular or serologic testing. Treatment depends on the etiology and severity and includes granulocyte colony-stimulating factor, immunosuppressants, antimicrobial prophylaxis, and hematopoietic stem cell transplantation in selected cases.

Conclusion: Neutropenia is a multifactorial disorder requiring individualized evaluation and management. Advances in genetic and immunological diagnostics combined with targeted therapies have improved risk stratification and outcomes. Early recognition and a multidisciplinary approach are essential to reduce infection-related morbidity and prevent progression to hematologic malignancies in high-risk patients.

Background: Immune thrombocytopenia (ITP) is an autoimmune condition characterized by low platelet count and increased risk of bleeding. Several pathophysiological processes contribute to the disease, including complement activation by autoantibodies bound to platelet surfaces. This study aimed to assess complement levels in ITP patients and determine their correlation with clinical presentation and disease severity.

Patients and methods: This case-control study enrolled 40 patients (both sexes, aged 18-40 years) with primary ITP and 40 healthy controls. All participants underwent a comprehensive health assessment, thorough physical examination, laboratory investigations, and abdominal ultrasound. These included a complete blood count (CBC) with blood film, renal and hepatic function tests, hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCV-Abs), human immunodeficiency virus (HIV) antibodies, hepatitis B core antibody (HBcAb), C-reactive protein (CRP), antinuclear antibody (ANA), thyroid-stimulating hormone (TSH), erythrocyte sedimentation rate (ESR), serum complement levels (C3 and C4), and Helicobacter pylori antigen in stool.

Results: Mean C3 and C4 levels were significantly lower in patients with ITP than in healthy controls. A statistical significant negative correlation was found between CRP and C4 levels in ITP patients. However, no statistically significant relationship was observed between C3 and C4 levels and platelet count in ITP patients, regardless of the presence of bleeding complications.

Conclusion: Complement levels were significantly lower in patients with ITP than in healthy controls. Complement levels were also significantly lower in treatment-naïve patients than in patients who received treatment. Therefore, complement levels could serve as a valuable laboratory test for disease activity.

Purpose: Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS.

Methods: We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after allogeneic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases.

Results: Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days post-INO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR. Doppler ultrasonography revealed preserved portal vein flow (range 10.2-26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56-0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression.

Conclusion: Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor. These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.

Purpose: Primary mediastinal large B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma. Radiation therapy (RT) has served as the primary treatment option for PMBCL; however, its role has been questioned with the advent of intensified immunochemotherapy. This study aimed to investigate the role of consolidative RT in the primary treatment of PMBCL.

Methods: This single-center retrospective study analyzed the survival outcomes of 65 patients newly diagnosed with PMBCL. The patients were divided into three treatment groups: (1) EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab), (2) R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), and (3) R-CHOP with consolidative RT.

Results: The objective response and complete remission rates were 86.2% and 63.1%, respectively, with 3-year progression-free survival (PFS) and overall survival (OS) rates of 72% and 81%, respectively. All patients in the R-CHOP + RT group achieved an objective response with better PFS) than those who did not receive consolidative RT (p = 0.028), although there was no significant difference in OS (p = 0.102). Consolidative RT benefited patients with an initially bulky disease or insufficient end-of-treatment response. The predictive value of ¹⁸F-fluorodeoxyglucose positron-emission tomography-computed tomography (PET-CT) in assessing the treatment response in PMBCL was revalidated, showing that patients who achieved negative end-of-treatment PET-CT had significantly better survival outcomes than others.

Conclusions: R-CHOP is a useful alternative regimen when intensified chemotherapy is not feasible. Consolidative RT should be considered in cases with an initially bulky disease and insufficient end-of-treatment response.

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.