Expert Review of Hematology最新文献

{"title":"An interview with Dr. Jean A. Yared on his experience as an investigator for obecabtagene autoleucel - by Reegan Burnell-Clarke (Commissioning Editor).","authors":"Jean A Yared","doi":"10.1080/17474086.2025.2524219","DOIUrl":"10.1080/17474086.2025.2524219","url":null,"abstract":"","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-3"},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in non-Hodgkin lymphoma mortality: global, regional, and national insights from 1990 to 2021.","authors":"Fangna Gu, Li Zhang","doi":"10.1080/17474086.2025.2522959","DOIUrl":"10.1080/17474086.2025.2522959","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Research design and methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-10"},"PeriodicalIF":2.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of pyruvate kinase activator in treating hemolytic anemias: a systematic review.","authors":"Syed Hassan Ahmed, Laila Tul Qadar, Jawad Ahmed, Zohaib Yousaf, Afsana Ansari Shaik, Muhammad Sohaib Asghar","doi":"10.1080/17474086.2025.2522295","DOIUrl":"10.1080/17474086.2025.2522295","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Registration: </strong>A protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) before study initiation, CRD42024598980.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-16"},"PeriodicalIF":2.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-106b-5p, MiR-200c-3p, and MiR-146a-5p expression as putative biomarkers for disease state in primary immune thrombocytopenia.","authors":"Reham Salah El Zaiat, Mai A H Abouelenin, Amany A Saleh, Mahmoud El-Hawy, Iman Aly Ahmedy, Manal Monir Mansour","doi":"10.1080/17474086.2025.2522298","DOIUrl":"10.1080/17474086.2025.2522298","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Research design and methods: </strong>Three groups were recruited in this study: newly diagnosed ITP children (<i>n</i> = 25) in group I, chronic ITP children (<i>n</i> = 25) in group II, and normal controls (<i>n</i> = 25) in group III. Plasma levels of miR-106p-5p, miR-200c-3p, and miR-146a-5p were measured by polymerase chain reaction.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-8"},"PeriodicalIF":2.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current state-of-the-art of immunotherapy in follicular lymphoma.","authors":"Sean McKeague, Phil Thompson, John F Seymour","doi":"10.1080/17474086.2025.2522956","DOIUrl":"10.1080/17474086.2025.2522956","url":null,"abstract":"<p><strong>Introduction: </strong>The advent of immunotherapy has rapidly changed the treatment landscape of follicular lymphoma (FL).</p><p><strong>Areas covered: </strong>Autologous CD19 chimeric antigen receptor <i>T</i>- 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.</p><p><strong>Expert opinion: </strong>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.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-13"},"PeriodicalIF":2.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obecabtagene autoleucel, a novel CD19-directed CAR T-cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia: the future for reducing toxicity and T-cell exhaustion?","authors":"Jean A Yared, Ariel Fromowitz, Mehmet Kocoglu, Nancy Hardy, Djordje Atanackovic, Aaron P Rapoport","doi":"10.1080/17474086.2025.2523551","DOIUrl":"https://doi.org/10.1080/17474086.2025.2523551","url":null,"abstract":"<p><strong>Introduction: </strong>Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL) continue to face poor outcomes despite recent advances in immunotherapy. The development of chimeric antigen receptor (CAR) T-cell therapies has transformed the treatment landscape, yet challenges such as severe cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and limited T-cell persistence have hindered their broader applicability. Obecabtagene autoleucel (obe-cel), a novel CD19-directed CAR T-cell therapy featuring a fast off-rate binding domain, represents a significant innovation aimed at optimizing the balance between efficacy and toxicity in this high-risk population.</p><p><strong>Areas covered: </strong>This review examines the pharmacologic and clinical development of obe-cel, with a focus on the unique receptor design that mimics physiologic T-cell receptor interactions to mitigate overactivation and exhaustion. Data from early-phase and pivotal trials, particularly the FELIX phase Ib/II study, are discussed in detail, highlighting efficacy outcomes such as a 77% overall remission rate and favorable safety profile with low rates of grade 3 or higher CRS (2.4%) and ICANS (7.1%). A comprehensive literature search was conducted using PubMed and clinical trial databases to identify peer-reviewed publications, reports, ongoing studies, and regulatory updates relevant to obe-cel and comparable therapies in R/R B-ALL.</p><p><strong>Expert opinion: </strong>Obe-cel represents an important conceptual advancement in CAR T-cell therapy, offering a promising alternative to existing high-affinity CD19 CARs. The integration of kinetic receptor engineering and split-dose administration appears to enhance both safety and durability of response, potentially redefining treatment goals in R/R B-ALL. As real-world experience and longer-term data accrue, obe-cel may emerge not only as a bridge to transplantation but also as a definitive therapy for select patients. The success of this approach may inform future CAR design across hematologic malignancies and support a paradigm shift toward receptor-tuned cellular immunotherapies.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determining treatment pathways for older patients with acute myeloid leukemia: patient and clinician perspectives.","authors":"Esther N Oliva, Antonio Almeida","doi":"10.1080/17474086.2025.2521397","DOIUrl":"10.1080/17474086.2025.2521397","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Areas covered: </strong>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.</p><p><strong>Expert opinion: </strong>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.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-10"},"PeriodicalIF":2.3,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preformed anti-HLA DQA1/DQB1 DSA possibly responsible for graft failure in haploidentical stem cell transplantation.","authors":"HeHua Wang, Jing Cheng, Fan Zhang, JunXun Li","doi":"10.1080/17474086.2025.2522307","DOIUrl":"10.1080/17474086.2025.2522307","url":null,"abstract":"<p><strong>Background: </strong>Primary graft failure (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplants (HSCT) and is associated with poor outcomes. Most clinical studies have focused on donor-specific anti-HLA antibodies (DSAs) against HLA-A, -B, and -DR molecules.</p><p><strong>Research design and methods: </strong>We present the first reported case of PGF associated with a preformed high-level DSA against HLA-DQ alone. The 39-year-old patient was diagnosed with acute myeloid leukemia. She received a haploidentical graft from her son and suffered PGF. She had persistently high levels of DSAs against her son's HLA-DQA1 and HLA-DQB1 molecules after desensitization. No alternative donor was available.</p><p><strong>Results: </strong>To circumvent the second graft failure, we adopted an approach of combining two units of unrelated cord blood (CB) and G-CSF-primed bone marrow (BM) and peripheral blood stem cells (PBSCs) from her son's transplants. The BM short tandem repeats (STRs) assay showed that one unit of the CB was fully engrafted, and the grafts from her son still failed to engraft.</p><p><strong>Conclusions: </strong>We conclude that high levels of anti-HLA DQA1/DQB1 DSA could be associated with PGF in our case. Besides DSAs against HLA-A, -B, and -DR, attention should also be paid to DSAs against the HLA-DQ molecule.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-5"},"PeriodicalIF":2.3,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of marstacimab in patients with hemophilia A and B: a systematic review and meta-analysis.","authors":"Muhammed Edib Mokresh, Omar Alomari, Sena Mokresh, Cagla Sumeyye Caliskan, Merve Kabasakal Ilter","doi":"10.1080/17474086.2025.2522296","DOIUrl":"10.1080/17474086.2025.2522296","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Nine manuscripts were included. Marstacimab significantly reduced the annualized bleeding rate (mean difference: -16.30; 95% CI: [-18.46, -14.15], <i>p</i> < 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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Registration: </strong>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.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-12"},"PeriodicalIF":2.3,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence, prevention and management of severe infections in patients undergoing therapy for chronic lymphocytic leukemia.","authors":"Arianna Bevilacqua, Alessandro Cellini, Francesco Angotzi, Andrea Serafin, Federica Mazzetto, Nicolò Danesin, Francesco Piazza, Livio Trentin, Andrea Visentin","doi":"10.1080/17474086.2025.2523552","DOIUrl":"10.1080/17474086.2025.2523552","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic Lymphocytic Leukemia (CLL) is a disease marked by high infectious risk due to a combination of patient, disease and treatment-related factors. As a new landscape in the therapeutic panorama is emerging with the introduction of novel agents, it is essential to understand their impact on the incidence of infectious events and consequently what prevention and management strategies should be introduced.</p><p><strong>Areas covered: </strong>We searched the PUBMED database considering peer-reviewed papers published between January 2013 and January 2025 that reported on at least 100 patients and provided detailed information on infectious complications. Retrospective studies, pooled analyses, and commentaries were excluded.</p><p><strong>Expert opinion: </strong>Infections are a considerable adverse effect that can occur in CLL patients under treatment, with their incidence being influenced by intrinsic biology of the disease, the number of prior lines of therapy, and treatment duration. This being considered, the initiation of fixed duration therapy combined with the use of preventive measures, such as immunoglobulin replacement therapy and vaccination programs, should be preferred whenever feasible.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-13"},"PeriodicalIF":2.3,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}