Expert Review of Hematology最新文献

Introduction: Leukocyte adhesion deficiency (LAD) is a rare genetic disorder that impairs leukocyte migration, leading to severe immune dysfunction and recurrent infections. Although allogeneic hematopoietic cell transplantation (HCT) remains the primary curative treatment for severe LAD, it is complicated by a high incidence of graft-versus-host-disease (GVHD).

Areas covered: This narrative review outlines the key factors influencing GVHD development in patients with LAD-I, the most common LAD subtype, undergoing HCT. It explores established and emerging strategies for preventing GVHD, focusing on their effectiveness and outcomes. The literature search was conducted using PubMed to identify studies reporting HCT for LAD published 1989-2025.

Expert opinion: Conventional GVHD prophylaxis regimens, primarily involving calcineurin inhibitors, have proven insufficient in preventing GVHD in high-risk populations. Among patients undergoing haploidentical HCT, post-transplantation cyclophosphamide has shown efficacy in preventing GVHD, although these results were based on limited cases. Graft manipulation techniques such as CD34⁺ selection have also been explored. However, these approaches are often associated with high graft failure rate and poor survival. Alemtuzumab, which is used in conditioning regimens, has shown promise in lowering GVHD incidence. Further studies are essential to optimize GVHD prophylaxis and improve survival outcomes in patients with LAD undergoing HCT.

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).