Expert Review of Hematology最新文献

Background: Polycythemia vera (PV) is characterized by erythrocytosis and an increased risk of thrombotic events (TEs). Currently, standard-of-care therapies for PV have limitations, which indicate the need to understand real-world treatment patterns and treatment burden in PV.

Research design and methods: This retrospective observational study analyzed real-world claims data in adult patients with PV using the Komodo Health claims database (2016-2022) in the United States. Burdensome treatment was classified as patients receiving ≥ 3 phlebotomies (PHLs) within a 6-month period and/or high-dose hydroxyurea (HU) ≥ 1,000 mg per day.

Results: Of 44,766 treated patients (mean age: 65 years; 64% male), 55% received burdensome treatment, which included frequent PHL (33%), high-dose HU (17%), or a combination of both (frequent PHL + high-dose HU, 5%). PHL and HU were the most common first-line treatments (PHL, 71%; HU, 27%), and 87% of patients initiating treatment with PHL monotherapy never advanced to another therapy regimen. TEs occurred in 16% of the treated patients.

Conclusions: These data suggest a substantial proportion of patients with PV receive burdensome treatments, with 55% of treated patients receiving frequent PHL and/or high-dose HU, highlighting need for therapy optimization. However, inherent limitations of using claims data should be taken into consideration.

Introduction: Down Syndrome (DS) is the most common human aneuploid abnormality. However, no association has been established between the presence of DS in Acute Lymphoblastic Leukemia (ALL) patients to affect survival rates.

Methods: We searched in Medline, Scopus, and Web of Science databases for relevant studies. Binary outcomes were evaluated using risk ratios (RRs) with 95% confidence intervals (CIs). The risk of bias was performed using the Newcastle - Ottawa Scale (NOS). We included randomized controlled trials and cohort studies, with patients with newly diagnosed ALL and excluded studies with overlapping, reviews, animal model studies, or letters. All endpoints were analyzed using random-effect models. Heterogeneity was assessed using I² statistics. Statistical analyses were performed using R, version 4.2.3.

Results: Sixteen studies, comprising 63,054 patients, were included. The outcomes demonstrated a significant difference favoring the ALL group for the outcomes as induction failure (RR 5.51 95% CI 3.50-8.69; p < 0.001); treatment-related mortality (RR 4.29 95% CI 3.38-5.45; p < 0.001), and total relapse (RR 1.28 95% CI 1.08-1.53; p = 0.004). There was no significant difference between the groups for event-free survival (5 years) groups (RR 0.91 95% CI 0.74-1.13; p = 0.40) and central nervous system relapse (RR 0.98 95% CI 0.55-1.72; p = 0.93).

Conclusions: This meta-analysis found a significant difference when comparing the DS-ALL group with the ALL group, the results supported a higher risk of induction failure, treatment-related mortality, and total relapse in the DS-ALL group.

Registration: The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO), National Institute for Health and Care Research (NIHR), with registration number CRD5689342.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy is used to treat several types of relapsed and refractory hematological malignancies and is associated with cognitive side-effects. The accurate diagnosis of cognitive impairment following CAR-T requires knowledge of baseline cognitive status prior to the therapy.

Research design and methods: Adult patients with advanced hematologic or solid organ malignancies underwent cognitive assessment, including a self-report questionnaire of psychopathology and subjective cognitive function, prior to receiving CAR-T. A subset of individuals also completed the Montreal Cognitive Assessment (MoCA) to examine utility of cognitive screening.

Results: Of 60 patients included, 16 (27%) had cognitive impairment, with six unique patterns of dysfunction. Memory impairment was the most common finding (15%). Impaired patients were more likely to have B-cell acute lymphoblastic leukemia (p = 0.024, BF₁₀ = 9.30), be younger (p = 0.007, BF₁₀ = 7.76), have bone marrow involvement (p = 0.037, BF₁₀ = 5.18), or have evidence of psychopathology (p = 0.004, BF₁₀ = 31.30). Analyses did not support the utility of cognitive screening. Of those patients who completed a self-report measure of psychopathology, nine (16%) were elevated on at least one symptom domain.

Conclusions: The findings demonstrate a broad spectrum of cognitive and psychological symptoms, emphasizing the importance of baseline evaluation for detecting cognitive symptoms that might arise after CAR-T.

Introduction: Hodgkin lymphoma (HL) is a curable disease; however, 10-20% of patients experience relapsed/refractory disease. While autologous hematopoietic cell transplantation (auto-HCT) remains standard, a substantial proportion relapse, necessitating alternative strategies. Allogeneic HCT (allo-HCT) remains a potentially curative option and here we emphasize the role of reduced-intensity conditioning (RIC) in HL.

Areas covered: In this review, we compare the feasibility, efficacy, and safety of myeloablative conditioning (MAC) and RIC allo-HCT in relapsed/refractory HL. Additionally, we describe the evolving landscape of transplantation in HL with the use of novel agents, especially immune checkpoint inhibitors, the role of alternative donors especially for ethnic minorities, and the evolving literature on the role of post-transplant Cyclophosphamide (PTC) in improving outcomes.

Expert opinion: Allo-HCT remains a potentially curative option for patients with relapsed/refractory HL. RIC allo-HCT has emerged as the preferred platform for most patients, offering a favorable balance between efficacy and tolerability by leveraging graft-versus-malignancy (GVM) effects while minimizing non-relapse mortality over myeloablative conditioning. The use of ICI in the first line has significantly altered post-transplant outcomes by enhancing GVM effects but also increasing the risk of graft-versus-host disease (GVHD). PTCy-based prophylaxis and optimized donor selection now enable the safer use of alternative donors without compromising outcomes.

Background: Mesenchymal stromal cells (MSCs) have emerged as a potential alternative therapeutic strategy for the prophylaxis of graft-versus-host disease (GVHD) in patients undergoing hematopoietic stem cell transplantation (HSCT).

Research design and methods: This meta-analysis included eight randomized controlled trials (RCTs) involving 570 patients. The primary outcomes assessed were overall survival (OS), the development of acute GVHD(aGVHD), and chronic GVHD (cGVHD). The statistical analysis was performed using Review Manager (RevMan 5.4) with a random-effects model.

Results: The meta-analysis showed a significant improvement in overall survival in the MSC group compared to the control group (RR 1.12; 95% CI: 1.02-1.23), with no evidence of heterogeneity (I² = 0%). MSC prophylaxis was associated with a significant reduction in the incidence of aGVHD (RR 0.67; 95% CI: 0.40-0.83) and cGVHD (RR 0.65; 95% CI: 0.49-0.87). However, no significant difference was found between the MSC and control groups regarding primary disease relapse (RR 1.00; 95% CI:0.73-1.38) or the incidence of infections (RR 0.80; 95% CI:0.57-1.11). In terms of patients with at least one adverse event, no statistically significant difference was observed between the two groups (RR 1.10; 95% CI: 0.74-1.63).

Conclusions: MSC prophylaxis significantly improves overall survival and reduces the incidence of both aGVHD and cGVHD in HSCT patients, without increasing the risk of relapse, infections, or adverse events, indicating its potential as a safe and effective intervention for GVHD management. Further large-scale, multicenter RCTs are needed to validate or refute the current findings.

Registration: This review has been registered with theInternational Prospective Register of Systematic Reviews (PROSPERO)(CRD42024569358).

Background: Cytogenetic tests are essential prognostic indicators for patients diagnosed with multiple myeloma (MM). The study aimed to evaluate the prevalence of cytogenetic abnormalities and their prognostic significance in patients with newly diagnosed MM.

Research design and methods: A cohort study involving 88 cases. Malignant plasma cells were isolated, and interphase fluorescent in situ hybridization was performed on bone marrow samples.

Results: The gain of 1q was observed in 17 (19%) patients, followed by t(4;14) in 10 (11.5%), and the 17p or P53 mutation was found in only 6 (7%) patients. Three patients (3.5%) exhibited t(14;16). Amplification of 1q was not detected in any of the samples. The presence of t(4;14), anemia, renal disease, a revised myeloma comorbidity index (R-MCI) of 7-9, and a lack of treatment response were associated with poor progression-free survival. Additionally, t(4;14), anemia, elevated LDH, an R-MCI of 7-9, and absence of maintenance treatment correlated with decreased overall survival. In the Cox regression analysis, the presence of t(4;14) and an R-MCI of 7-9 were the most significant factors predicting worse outcomes.

Conclusions: The t(4;14) and RMCI are reliable predictors of poor survival in newly diagnosed MM patients.

Introduction: Hemophilia A and B are lifelong bleeding disorders traditionally managed with factor replacement therapy. While effective, this approach is limited by frequent infusions, inhibitor development, and high treatment costs, underscoring the need for innovative therapies that improve patient outcomes and quality of life.

Areas covered: This review explores recent advances in hemophilia management, focusing on extended half-life factor concentrates, non-factor therapies, such as bispecific antibodies and rebalancing agents, and the emergence of gene therapy as a potential functional cure. English-language studies on hemophilia therapies were searched in PubMed, Embase, Web of Science, and ClinicalTrials.gov (Jan 2014 to Apr 2025). A comprehensive literature review was conducted, covering pivotal clinical trials, real-world data, and translational research addressing both efficacy and safety considerations.

Expert opinion: Innovative therapies are transforming hemophilia care, offering simplified administration, superior bleed prevention, and new hope for patients with inhibitors. Gene therapies mark a milestone, but present challenges related to durability, immune response, and cost. Personalized treatment strategies, integrating patient-specific factors and shared decision-making, are essential to optimizing outcomes. Continued research, long-term surveillance, and efforts to improve global access will define the next era of hemophilia management, moving closer to a future where patients can lead lives free from the burden of bleeding.

Background: LINC00652 plays pivotal roles in acute lymphoblastic leukemia (ALL) a heterogeneous hematological malignancy. Here, we investigated the potential regulatory mechanisms of LINC00652 in ALL.

Research design and methods: Genome-wide association study data for LINC00652 were obtained for Mendelian randomization and integrated with RNA sequencing data, Bioinformatics analyses, including weighted gene co-expression network analysis (WGCNA), Spearman or Pearson correlation analysis, function, immune microenvironment, subcellular localization, and competing endogenous RNA (ceRNA) network construction, were employed explore the potential mechanisms of LINC00652 in ALL.

Results: LINC00652 exhibited no significant causal relationship with ALL but was identified as a protective factor (p > 0.05). LINC00652 levels were significantly decreased in patients with ALL, while WGCNA demonstrated the significance of black and blue modules for ALL. Seventy-nine messenger RNA (mRNAs) (SYT7) significantly correlated with LINC00652 (p > 0.05) and were enriched in the Janus kinase/signal transducer and activator of transcription (STAT), interleukin 2-STAT5, apoptosis, and adipogenesis pathways. Twenty-eight immune cells infiltrated the ALL, with immature B-cells and gamma delta T-cells significantly associated with LINC00652 expression (p < 0.05). LINC00652 was predominantly cytoplasmic, and a ceRNA network involving LINC00652, 36 microRNAs, and 18 mRNAs were proposed.

Conclusions: LINC00652 May protect against ALL and influence its pathogenesis through ceRNA mechanisms.