Expert Review of Hematology最新文献

Introduction: Prophylaxis is the recommended management strategy for all persons with hemophilia (PwH), yet its adoption is uneven worldwide.

Areas covered: This analysis examines global disparities in hemophilia care, focusing on global prophylactic coverage and its correlation with the World Bank's world development indicators. It outlines the disproportionate consumption of clotting factors and non-factor concentrates in high-income countries compared to lower-income counterparts and the challenges of expanding prophylaxis coverage in under-resourced settings. The analysis integrates socioeconomic data with global health indicators to understand these disparities and advocates for increased distribution of treatment resources across all income levels, emphasizing the need for policy changes to improve hemophilia care worldwide. Studies addressing the prophylaxis perspectives in hemophilia were selected using PubMed and Google Scholar platforms (unlimited time frame). Articles were supplemented with WFH's annual surveys and guidelines, including the WFH Global Survey 2022, WFH Guidelines for the Management of Hemophilia 2020 and World Bank data.

Expert opinion: Significant disparities in hemophilia care and factor usage exist between high-income and lower-income countries. Standardized, harmonized metrics for different types of factor consumption are critical to accurately assess and compare hemophilia care on an international basis.

Introduction: Patients undergoing revascularization of the lower extremities have unacceptably high rates of major adverse cardiac and limb events despite the routine use of antiplatelet therapy. Optimization of antithrombotic therapy provides an opportunity to reduce this risk. Recent large, randomized trials have demonstrated substantial benefit from the combination of low-dose rivaroxaban and aspirin compared with aspirin alone. Despite this new evidence, uptake remains limited.

Areas covered: This review will outline the drug profile of rivaroxaban, summarize the key efficacy and safety data for the combination of low-dose rivaroxaban and aspirin following lower extremity revascularization, and examine barriers to therapy uptake.

Expert opinion: Combination of low-dose rivaroxaban and aspirin is the only antithrombotic regimen that has been shown to reduce both cardiac and limb events following peripheral revascularization while maintaining an acceptable bleeding profile. Single and dual antiplatelet therapy have limited randomized evidence for this indication, but are commonly used. An important contributor is the failure of major societal guidelines to incorporate this new evidence. Moving forward, there is an urgent need to update these guidelines. Further evaluation of the efficacy and safety of dual antiplatelet therapy will help to inform optimal antithrombotic therapy after lower extremity revascularization.

Background: In patients with thalassemia, different organs are affected differently by iron overload. Nevertheless, the reasons for this could be the same key transporters. This study investigated the iron deposition in different organs of transfusion-dependent thalassemia (TDT) patients and its correlation.

Research design and methods: This cross-sectional study involved 54 TDT patients who underwent MRI T2* examinations of the heart, liver, pancreas, spleen, kidneys, and pituitary. The study analyzed the iron deposition in each organ and evaluated the correlation of iron deposition using Spearman's test.

Results: Among the 54 patients with TDT, liver iron overload was found in 49/54 (90.7%) cases, pancreas iron overload in 43/54 (79.6%) cases, spleen iron overload in 18/26 (69.2%) patients, heart iron overload in 20/54 (37.0%) cases, and kidney iron overload in 8/54 (14.8%) patients. Most patients (66.7%) with iron overload in the liver but not in the heart exhibited spleen iron abnormalities. Pituitary T2* and pancreas T2* (r = 0.790), pituitary T2* and kidney T2* (r = 0.692), kidney T2* and pancreas T2* (r = 0.672) showed positive correlation (all p < 0.05).

Conclusions: Patients with TDT exhibited significant organ-specific iron overload. These findings highlight the importance of routine MRI screening for monitoring and managing iron overload in patients with TDT. Pituitary, pancreas, and kidney may have similar iron-loading mechanisms.

Introduction: Von Willebrand disease (VWD) reflects the most common inherited bleeding disorder, arising from defects or deficiencies in the von Willebrand factor (VWF). VWD treatment mostly relies on the replacement of missing or defective VWF, but additional ('adjunct') therapies are useful in select patients/situations. Patients with VWD are often misdiagnosed and therefore non-optimally managed.

Areas covered: We provide a narrative review, following relevant literature searches in PubMed related to the topic up to September 2024. After an overview of VWF, VWD, and current treatments, we explore the use of nonstandard or emerging therapies for VWD. For example, FVIII replacement or antibody-based FVIII bypassing strategies (e.g. emicizumab) may prove useful in some cases or in initial treatment of certain VWD patients, including those with type 2N or 3 VWD, or those with inhibitors. Additional emerging therapies may also be useful, including hemostasis rebalancing agents.

Expert opinion: Just as hemophilia is experiencing a renaissance of treatment options, so too will the landscape of VWD treatment change over time. This will be fueled by the concept of personalized treatment, meaning potentially different treatments for different VWD patients, or for given patients according to treatment aims.

Background: B-cell lymphoma, a diverse malignancy, is intricately regulated by multiple factors. MicroRNAs (miRNAs) have been demonstrated to be important regulators of the initiation and progression of human B-cell lymphoma, but their functions need to be further explored.

Research design and methods: Two B-cell lymphoma cell lines, Romas and HBL-1, were engineered to overexpress miR-451, with cell proliferation assessed via cell counting assays. Flow cytometry was used to study the effects of miR-451 on cell cycle and apoptosis. Bioinformatics analyses were performed using GEO datasets (GSE181063, GSE32918, GSE56315) to identify DEGs, and potential miR-451 target genes were predicted using tools like ENCORI, TargetScan, and R packages. A risk model for DLBCL prognosis was developed using Cox and LASSO regression. qRT-PCR validated the expression of these target genes.

Results: This study revealed that miR-451 inhibited cell proliferation, arrested the cell cycle, and induced apoptosis in human DLBCL cell lines. Bioinformatics analysis identified 9 target genes (MMP9, AQP9, RIN2, EOMES, LCP2, SELPLG, MAL, SOCS5, S1PR3) significantly associated with DLBCL prognosis, suggesting a potential mechanism by which miR-451 suppresses DLBCL development.

Conclusions: Our study indicates that a specific set of miR-451 target genes may significantly influence DLBCL patient outcomes.

Introduction: The disruption of the JAK/STAT signaling pathway is a defining feature of myelofibrosis (MF). The introduction of JAK inhibitors (JAKi) has transformed the therapeutic approach to MF, becoming essential to treatment and reshaping the management landscape. While JAKi are now the preferred first-line treatment for most patients, various management options are available for those who do not respond to initial therapy.

Areas covered: This review focuses on management options for patients with MF, with particular emphasis on therapeutic strategies following the failure of first-line JAKi. It provides a comprehensive overview of the current treatment landscape, including alternative JAKi and other approaches. The review is based on an extensive literature search using available databases (PubMed, Cochrane …) and relevant web resources (clinicaltrials.gov).

Expert opinion: Ruxolitinib benefits in MF often diminish after 3-4 years, with complications like thrombocytopenia and anemia. Three newer JAKi offer alternatives with similar efficacy and varied side effects. Stem cell transplantation is a curative option for a minority, ideally timed at peak response to JAKi. Research aims to enhance first-line treatments and restore responses in resistant patients. Future therapies may include novel combinations or immunotherapies targeting specific mutations, requiring collaboration between patient, clinical, and pharmaceutical communities.

Introduction: The development of oral therapies impacts the management of acute myeloid leukemia and myelodysplastic syndromes, especially for targetable mutations including IDH1/2.

Areas covered: We discuss IDH1/2 activity and inhibitor therapy in various settings, including monotherapy, combination therapy with hypomethylating agents, and other approaches.

Expert opinion: Olutasidenib, enasidenib, and ivosidenib are approved for relapsed AML. Ivosidenib is approved for relapsed MDS and alone or with azacitidine in newly diagnosed AML. However, unanswered questions exist. In newly diagnosed AML, ivosidenib + azacitidine shows a survival benefit compared to azacitidine, but it is unknown whether ivosidenib + azacitidine demonstrates improved survival compared to ivosidenib. Ivosidenib + azacitidine demonstrated a survival benefit not seen with enasidenib + azacitidine. It is unclear whether newly diagnosed AML should be treated with azacitidine + ivosidenib or azacitidine + venetoclax. Azacitidine + venetoclax shows excellent response rates in IDH mutated disease. Retrospective data show low response rates of IDH inhibitor therapy post-venetoclax whereas HMA + venetoclax retains activity post IDH inhibition. The role of IDH inhibition post-transplant is unclear. Single-arm studies show post-transplant maintenance is safe; however, randomized trials are needed. Similarly, IDH inhibitors can be combined with chemotherapy however randomized studies are needed.

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated intravascular hemolysis (IVH). Current treatments like Eculizumab and Ravulizumab have limitations, with many patients still requiring transfusions. This study aimed to investigate the safety and efficacy of the new emergent treatment called Danicopan.

Methods: We systematically searched five electronic databases - Epistemonikos, Web of Science, Medline, Scopus, and ClinicalTrials - to ensure comprehensive coverage. The systematic review was conducted following the PRISMA guidelines, ensuring methodological rigor.

Results: Four studies were eligible for inclusion, all of them were multicenter trials with 79 patients studied. Treatment with Danicopan led to a notable improvement in hemoglobin levels and a decrease in reticulocyte counts. However, LDH levels did not significantly change after treatment. Additionally, there was a significant increase in GPI-deficient erythrocytes but not in GPI-deficient granulocytes. Total and direct bilirubin levels showed significant differences between treatment groups, and there was an improvement in FACIT scores from baseline.

Conclusions: Our systematic review and meta-analysis support the potential of Danicopan as a viable therapeutic option for PNH patients. The targeted inhibition of factor D within the complement system by Danicopan demonstrates both safety and efficacy in managing PNH, as evidenced by our findings.

Registration: This paper was registered with the PROSPERO database (CRD42024499375).

Background: This study aimed to investigate the demographic, clinical, and diagnostic aspects of adult pancytopenia while exploring its etiological spectrum through hematological parameters and bone marrow studies.

Research design and methods: This observational study involved 117 adult individuals ranging from 13 to 85 years who presented with pancytopenia. A comprehensive examination of demographic features, hematological parameters, clinical presentations, and physical findings, including liver and spleen characteristics, was conducted. Additionally, serological analyses for HBsAg and Anti HCV were performed. The diagnostic spectrum was determined through bone marrow studies.

Results: Pancytopenia manifested with varied clinical symptoms, with generalized weakness (72.65%), fever (64.1%), dyspnea (54.70%), bleeding (34.2%), and weight loss (25.6%) being prominent. Physical examination revealed a range of liver and spleen characteristics, with hepatomegaly observed in 32.48% and splenomegaly in 44.4% of cases. Serological findings indicated HBsAg positivity in 8.5% and Anti HCV positivity in 21.37% of cases. The diagnostic distribution encompassed diverse conditions, with aplastic anemia (17.1%), megaloblastic anemia (12.8%), and myelodysplastic syndromes (12.8%) being prevalent.

Conclusions: This study provides a comprehensive overview of the demographic, clinical, and diagnostic aspects of pancytopenia. The observed prevalence of different diagnoses underscores the necessity of a thorough evaluation, including bone marrow studies, for accurate diagnosis and appropriate management.

Background: Multiple myeloma (MM) is a malignant incurable disease characterized by monoclonal plasma cell increase associated with renal impairment. Evaluation of neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), hemoglobin/red cell distribution width (HB/RDW), interleukin-20 (IL-20), and vascular endothelial growth factor-A (VEGFA) in patients with MM (with or without renal impairment) as prognostic and severity indicators.

Research design and methods: A cross-sectional study was conducted on sixty MM patients with renal impairment, sixty MM patients without renal impairment, and sixty subjects (control group). Complete blood count, IL-20 immunoassay, and gene expression of IL-20, and VEGFA were evaluated.

Results: Higher levels of NLR, MLR, and IL-20, and moreover lower levels of PLR, HB/RDW, as well as upregulation of IL-20, and VEGFA gene expression were detected in MM patients, especially those with renal impairment. Receiver operating characteristic curves analysis of NLR, MLR, PLR, and IL-20 showed high sensitivity and specificity in the diagnosis of MM and disease stages.

Conclusions: NLR, MLR, PLR, HB/RDW, IL-20, and VEGFA may be implicated in the inflammatory process of MM and renal impairment pathogenesis. NLR, MLR, and IL-20 can be used as prognostic markers in MM stages.