Expert Review of Hematology最新文献

Introduction: Despite being the leading causes of morbidity and mortality worldwide, very little is known about the similarities and differences between venous and arterial thrombi. This review is focused on comparing their structural, molecular, and temporal characteristics.

Methods: A systematic review following PRISMA guidelines and focusing on arterial and venous thrombi was conducted. Only studies having histological images in vivo from animal studies and humans were included. Data on structural components and temporal changes of thrombi were collected and analyzed.

Results: There were 76 articles found eligible from the full-text review. Only two studies had simultaneous temporal and spatial comparisons and did not attempt to compare the two types of thrombi: arterial and venous. Therefore, comparative insights were additionally drawn from studies analyzing one thrombus type in isolation. Four common factors were identified: red blood cells (RBCs), white blood cells (WBCs), platelets, and fibrin. Platelet concentration was higher in arterial thrombi, while more red blood cells (RBCs) were found in the venous thrombi.

Conclusions: There is a clear lack of direct comparison between arterial and venous thrombi, with limited information on their evaluations. Most available findings are derived from independently conducted analyses.

Registration: The protocol was registered on PROSPERO (registration ID: CRD420251003712).

Background: Molecular typing before hematopoietic stem cell transplantation (HSCT) at the eplet level is an emerging method to optimize HLA matching.

Materials and methods: Patients who received outpatient haploidentical HSCT (Haplo-HSCT) from a sibling after reduced intensity conditioning (RIC) were studied. HLA class I and II mismatched eplets (MEs) load was determined using HLAMatchmaker software. A cutoff > or < 10 MEs was used to assess outcomes.

Results: 114 patients were studied. A locus B MEs load > 10 was associated with decreased overall survival (OS), (p = 0.049), and increased graft failure (GF) (p = 0.004). Mortality was higher with > 10 MEs in HLA-I locus B (p = 0.025), and HLA-II DRB1 (p = 0.026); chronic GVHD was higher with > 10 MEs in DRB1 (p = 0.009). Anti-HLA donor-specific antibodies (DSA) were more frequent in recipients with > 10 MEs load at locus C (p = 0.021) and DRB1 (p = 0.002). MEs load > 10 at locus C and DRB1 were associated with anti-HLA DSA. Infection (p = 0.012), DSA (p = 0.014), and relapse (p = 0.001) were associated with lower OS, while multitransfusion (p = 0.035), aGVHD (p = 0.035) and infection (p = 0.021) with reduced event-free survival (EFS).

Conclusion: HLA MEs load > 10 in locus B was associated with reduced OS, and in locus DRB1 with higher death rate and cGVHD after outpatient sibling haplo-HSCT using RIC.

Introduction: Maintenance therapy plays a crucial role in prolonging progression-free survival and overall survival in multiple myeloma. Lenalidomide remains the gold standard, as demonstrated in phase 3 trials, consistently showing superior survival compared to observation or placebo. However, both established and novel agents - such as thalidomide and pomalidomide, proteasome inhibitors (PIs), monoclonal antibodies (moAbs), and bispecific antibodies - have been investigated as alternatives to assess their efficacy and safety.

Areas covered: This review delivers a comprehensive analysis of the current landscape of maintenance strategies in MM and presents the available evidence supporting the efficacy of novel agents, both as monotherapy and in combination.

Expert opinion: Maintenance therapy is a critical component of MM management, capable of improving disease control and survival. Lenalidomide has demonstrated its ability to extend patients' survival, but cumulative toxicity remains a significant concern. For high-risk patients, maintenance therapy with PIs and CD38-targeting moAbs has proven to improve outcomes. However, challenges such as quality of life, cost, accessibility, and treatment resistance persist. A minimal residual disease (MRD)-adapted maintenance strategy is desirable, particularly to enable personalized treatment approaches in clinical practice.

Background: Almost 50% of patients with FLT3-ITD AML relapse despite undergoing allogeneic hematopoietic stem cell transplantation (HSCT). FLT-3 inhibitors (FLT3i) can be used in a post-HSCT setting as a relapse prevention.

Research design and methods: We retrospectively compared 24 FLT3-mutated AML patients receiving post-HSCT SORA with a control group of 24 FLT3-mutated AML SORA-free individuals. SORA was initiated at a median of 2.9 months after transplantation. Median dosage was 600 mg daily with median treatment duration of 8.8 months. Due to toxicities, 16/24 patients required dose modifications with 6 early SORA withdrawals. After median follow-up of 20.7 months, 1 patient relapsed in SORA-group whereas 9 relapses were observed in the control group (p=0.004).

Results: SORA maintenance significantly improved OS and RFS probability when compared to the control group (36.3 vs 11.6 months; p = 0.01 and 95.5% and 66.7%; p = 0.004; respectively). SORA maintenance effectively reduced the risk of death by 93.6% for patients in complete remission with detectable measurable residual disease (p = 0.001). At the last follow-up, 4.2% of patients died in SORA-group when compared with 50% in the control group (p < 0.001).

Conclusions: SORA maintenance after HSCT diminishes the cumulative incidence of relapse as well as prolongs OS and RFS in FLT3-mutated AML.

Introduction: Von Willebrand factor (VWF) plays a crucial role in hemostasis: its interactions with endothelial matrices, platelets, and factor VIII make it a key player in both primary hemostasis and coagulation. Pathology associated with VWF spans mild to severe bleeding manifestations in the case of inherited von Willebrand disease (VWD), the most common congenital bleeding disorder, or acquired von Willebrand syndrome (AVWS). Conversely, VWF can be associated with thrombotic manifestations in situations related to inflammation, infection, or inherited or acquired ADAMTS13 defects.

Areas covered: This review article aims to provide guidance on the use and interpretation of clinical laboratory assays available to measure VWF and other factors related to VWD. Different VWF tests can be used in different clinical settings for efficient diagnosis and patient management. Assay limitations are also addressed.

Expert opinion: A myriad of laboratory assays, from first line to esoteric assays, exist to enable adequate diagnosis of VWD and other diseases influenced by VWF. Clinical investigations of VWF are complicated because VWF has multiple functions which variably depend on the patient's pathophysiological status. The right choice of assays is therefore critical to provide adequate diagnosis in due time and with reasonable analytical efforts.

Introduction: Outcomes of older patients with classic Hodgkin lymphoma (cHL) are inferior to those of younger patients secondary to their distinct clinical presentation, unique disease biology, increased burden of medical comorbidity, and poorer tolerance to conventional therapies. Greater attention to the objective parameters underlying patient fitness has led to the recognition of comprehensive geriatric assessments (CGA) as an important method to optimize selection for appropriate therapy intensity. Given the magnified risk associated with traditional chemotherapy in older patients with cHL, the incorporation of the novel agents brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) into modern treatment paradigms offers promise for improved outcomes in this population.

Areas covered: We describe historical outcomes in older patients with cHL, the underpinnings of traditional treatment strategies, the evolving therapeutic landscape via integration of novel therapies into the frontline and relapsed/refractory settings, and the importance of contextualizing therapy selection via formal CGAs.

Expert opinion: Novel therapies have broadened the array of therapeutic options for older patients with cHL eligible for either curative or palliative intent therapy. Further investigation into rational combinations of these drugs, together with ongoing efforts to validate cHL-specific CGAs, aim to improve outcomes for older patients across the spectrum of fitness.

Introduction: Achieving remission and prolonging duration of response are the primary treatment objectives for patients with acute myeloid leukemia (AML). However, identifying the best approach for older patients poses a significant challenge. This review explores the treatment pathways for older patients, especially those not eligible for stem cell transplantation and emphasizes the importance of optimizing outcomes by actively involving patients in their care plans.

Areas covered: There is currently no clinical consensus on when to use intensive or less-intensive induction chemotherapy for older patients, and more empirical evidence is needed. Meanwhile, this decision must still account for patients' preferences and circumstances in addition to the benefits and risks of therapy. Survey data have shown that patients want to be involved in their treatment decisions and that higher patient engagement improves patient-reported quality of care and satisfaction. While the importance of patient engagement is widely recognized, clinicians can work toward bridging the gap between patients' preferred and perceived levels of involvement in their treatment decisions.

Expert opinion: Patient engagement in treatment decisions is particularly important for older patients with AML. Understanding patients' perspectives and expectations for clinical and quality-of-life outcomes is essential to tailoring the most appropriate and effective treatment plan.

Background: The pathophysiology of primary immune thrombocytopenia (ITP) is complicated and multifactorial, including platelet antibody formation and T cell imbalance. Emerging evidence has revealed differential miRNA expression in autoimmune disorders, including ITP. Nevertheless, the role of miR-106b-5p, miR-200c-3p, and miR-146a-5p in ITP remains unclear. Herein, we explored the potential role of these miRNAs in pediatric ITP and examined how their plasma levels influenced response to therapy.

Research design and methods: Three groups were recruited in this study: newly diagnosed ITP children (n = 25) in group I, chronic ITP children (n = 25) in group II, and normal controls (n = 25) in group III. Plasma levels of miR-106p-5p, miR-200c-3p, and miR-146a-5p were measured by polymerase chain reaction.

Results: MiR-106b-5p and miR-200c-3p were upregulated, whereas miR-146a-5p was downregulated in newly diagnosed and chronic ITP versus controls. MiR-200c-3p and miR-146a-5p were much higher in chronic ITP than newly diagnosed ITP. Lower miR-106b-5p levels were associated with complete response.

Conclusions: MiR-106b-5p and miR-200c-3p were elevated, while miR-146a-5p was suppressed in ITP versus controls. Reduced miR-106b-5p indicated a full response to therapy. These markers may be useful as diagnostic ITP biomarkers. Moreover, miR-106b-5p level can be used to monitor response to therapy and as a predictor for complete response.

Background: Hemophilia A and B are life-threatening congenital bleeding disorders traditionally managed with frequent factor replacement therapies, often complicated by breakthrough bleeds and inhibitor development. Marstacimab, a monoclonal antibody targeting TFPI, has emerged as a novel prophylactic treatment to reduce bleeding episodes in patients without inhibitors.

Methods: A systematic review was conducted following PRISMA guidelines. A comprehensive literature search was performed across multiple databases. Meta-analysis was conducted using R, applying a random-effects model.

Results: Nine manuscripts were included. Marstacimab significantly reduced the annualized bleeding rate (mean difference: -16.30; 95% CI: [-18.46, -14.15], p < 0.001) and showed a favorable safety profile with most adverse events being mild or moderate, and no thrombotic events reported. The use of a prefilled pen device further highlighted the therapeutic benefits and ease-of-use of Marstacimab.

Conclusions: This meta-analysis reinforces the efficacy and safety of Marstacimab in reducing bleeding rates in severe hemophilia A and B. The findings support its role as a promising, transformative alternative to conventional factor replacement therapies.

Registration: The study protocol for this systematic review was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) database (www.crd.york.ac.uk/prospero/), and it was allocated the PROSPERO identification number CRD42024620215.