Expert Review of Hematology最新文献

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.

Introduction: The advent of immunotherapy has rapidly changed the treatment landscape of follicular lymphoma (FL).

Areas covered: Autologous CD19 chimeric antigen receptor T- cell (CAR-T) products show unprecedented efficacy in third-line FL but substantial rates of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Bispecific antibodies (BSAB) achieve deep and durable responses in heavily pretreated FL patients with less severe CRS and minimal neurological toxicity. BSAB have differing routes of administration, treatment duration and CRS prophylaxis. Checkpoint inhibitors show disappointing response rates in FL. Lenalidomide and tazametostat have modest single agent activity in FL, but synergize with other forms of immunotherapy.

Expert opinion: CAR-T offers a short duration of therapy with a potential plateau in progression free survival. Major disadvantages include cost, availability, requirement for lymphodepletion and toxicity. BSAB are available 'off the shelf,' have a comparably lower toxicity profile, and are ripe for combination. With both platforms, there are significant infectious risks. There are unanswered questions regarding when to use immunotherapy for FL, impact of disease burden, role of re-treatment and optimal sequencing/combinations. Moving forward, the field will need to develop new prognostic markers, reassess treatment indications, and focus on minimizing toxicity.

Background: Non-Hodgkin Lymphoma (NHL) is a group of hematological cancers with significant global mortality. Despite advances in treatment, mortality disparities persist across age, sex, region, and socioeconomic status, underscoring the need for a deeper understanding of global trends.

Research design and methods: Data from the Global Burden of Disease Study covering 204 countries between 1990 and 2021 were analyzed. The data were stratified by sex, age, and Socio-Demographic Index (SDI). Trends were assessed using the Estimated Annual Percentage Change (EAPC), and correlations with SDI were evaluated.

Results: From 1990 to 2021, global NHL deaths increased from 146,657 to 267,061, and death rates rose from 2.75 to 3.38 per 100,000 (EAPC: 0.51). Males and individuals aged 75 and older had higher mortality rates. High-SDI regions, including High-income North America (8.49 per 100,000) and High-income Asia Pacific (9.60 per 100,000), had the highest rates. Middle-SDI regions showed the most significant increases, while low-SDI regions experienced declines. Japan had a sharp rise in mortality (EAPC: 3.03), while Ethiopia had a decline (EAPC: -2.09).

Conclusion: NHL mortality increased globally from 1990 to 2021, with higher burdens in males and older adults. The fastest increases were observed in middle-SDI regions, reflecting healthcare disparities.

Introduction: Pyruvate kinase (PK) is an important glycolytic enzyme responsible for erythrocytic ATP production. PK allosteric activators have been shown to increase ATP and reduce 2,3-disphosphoglycerate among red blood cells leading to improved oxygen affinity, sickling, and hemolysis. In this systematic review, we aim to evaluate the efficacy and safety of PK activators in hemolytic anemias.

Methods: This study was conducted following the PRISMA guidelines. A literature search was conducted using relevant keywords over PubMed/Medline, Google Scholar, Cochrane Library, and clinicaltrial.gov, till 29 September 2024. Relevant data was extracted into a spreadsheet and synthesized qualitatively.

Results: The literature search yielded 7,153 results, with seven studies ultimately included in the review. These studies involved 206 patients, 166 of whom received mitapivat and the rest received placebo. Hemoglobin response was achieved by 38.0% to 80.0% of participants receiving mitapivat, with an average increase of 0.4 to 1.7 g/dL. Most studies reported improvements in bilirubin, lactate dehydrogenase, haptoglobin, and reticulocyte levels. Adverse events (AEs) were experienced by 93.2% of participants, with rates of 93.97% and 89.7% in the intervention and control groups, respectively. However, most AEs were mild and transient, and 23.4% were graded as 3 or higher.

Conclusions: In this study, PK activators, particularly mitapivat, demonstrated promising efficacy and safety profiles in managing hemolytic anemias. These agents significantly improved hemoglobin levels, markers of hemolysis, and hematopoietic response, offering a beneficial therapeutic option for various hemolytic conditions, including pyruvate kinase deficiency, sickle cell disease, and thalassemia.

Registration: A protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) before study initiation, CRD42024598980.

Background: Thrombosis is a major complication in polycythemia vera (PV), contributing to significant morbidity and mortality. This retrospective study aimed to develop a predictive model for thrombosis risk in PV patients using advanced statistical techniques.

Research design and methods: The study included 817 consecutive PV patients, with a median follow-up of 59 months. A Bayesian logistic regression model with sparsity-inducing R2D2 priors was used to predict thrombosis.

Results: Thrombotic events occurred in 13.2% of patients. The thrombosis group had significantly higher median neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), splenomegaly, cardiovascular risk factors, microvascular symptoms, pruritus, previous thrombosis, and Charlson Comorbidity Index (CCI) compared to the no-thrombosis group. Both groups were comparable in age. Multivariate regression analysis identified CCI, PLR, splenomegaly, and microvascular symptoms as key predictors of thrombosis. A clinical score, ThromboVera CS, was developed based on these predictors, classifying patients into low, moderate, or high-risk groups. In the low-risk group, 6.94% experienced thrombosis, compared to 15.76% in moderate-risk group and 48.78% in the high-risk group.

Conclusions: The ThromboVera CS score is a reliable, easy-to-use tool for predicting thrombosis in PV patients. It can help clinicians identify those at high risk, enabling early intervention that could significantly improve patient outcomes by targeting nearly 50% of high-risk patients.