American Journal of Hematology最新文献

{"title":"Targeting PIEZO1-TMEM16F Coupling to Mitigate Sickle Cell Disease Complications","authors":"Pengfei Liang, Yui-Chun S. Wan, Ke Z. Shan, Ryan Chou, Yang Zhang, Martha Delahunty, Sanjay Khandelwal, Samuel J. Francis, Gowthami M. Arepally, Marilyn J. Telen, Huanghe Yang","doi":"10.1002/ajh.70086","DOIUrl":"https://doi.org/10.1002/ajh.70086","url":null,"abstract":"A deeper understanding of sickle cell disease (SCD) pathophysiology is critical for identifying novel therapeutic targets. A hallmark of SCD is abnormal phosphatidylserine (PS) exposure on sickle red blood cells (RBCs), which contributes to anemia, thrombosis, and vaso-occlusive crises (VOC). However, the mechanisms underlying this excessive PS exposure remain unclear. Here, we identify TMEM16F, a Ca²⁺-activated lipid scramblase, as a key mediator of PS exposure downstream of Ca²⁺ influx through the mechanosensitive channel PIEZO1 in sickle RBCs. Electrophysiology, imaging, and flow cytometry reveal that deoxygenation-induced sickling activates PIEZO1, triggering Ca²⁺ entry, TMEM16F activation, and PS exposure. This cascade promotes PS⁺ microparticle release, thrombin generation, and RBC adhesion to endothelial cells. Notably, partial PIEZO1 inhibition with benzbromarone, an anti-gout drug, suppresses these effects. Our findings define a previously unrecognized mechanotransduction pathway in sickle RBCs and propose a unique therapeutic strategy to mitigate hypercoagulability and vaso-occlusion associated with SCD.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"10 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Thrombotic Risk of Thrombopoietin Receptor Agonists for Immune Thrombocytopenia Secondary to Systemic Lupus and Antiphospholipid Syndrome: French Experience With 80 Patients","authors":"Cindy Marques, Guillaume Moulis, Mickaël Roussotte, Bernard Bonnotte, Jean‐François Viallard, Julie Graveleau, Hervé Lobbes, Nathalie Costedoat‐Chalumeau, Alban Deroux, Delphine Gobert, Antoine Dossier, Laurent Gilardin, Olivier Lambotte, Mylène Dufrenoy, Matthieu Mahévas, Marc Michel, Pascal Sève, Bertrand Godeau","doi":"10.1002/ajh.70052","DOIUrl":"https://doi.org/10.1002/ajh.70052","url":null,"abstract":"Only few data are available regarding the efficacy and safety of thrombopoietin receptor agonists (TPO‐RAs) for treating systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS)‐associated immune thrombocytopenia (ITP). We retrospectively assessed the efficacy and safety of TPO‐RAs in 80 adults with ITP in three subgroups: (1) 37 patients with definite or incomplete SLE and no antiphospholipid antibodies (APAs), (2) 27 patients with definite or incomplete SLE associated with APAs and no history of arterial or venous thrombotic events (TEs) and (3) 16 patients with APS. In total, 39 (48.8%) patients received eltrombopag, 14 (17.5%) romiplostim and 27 (33.8%) both TPO‐RAs sequentially. The overall response of ITP was 78.8%. In total, 17 (21.3%) patients had 21 TEs (7 venous and 14 arterials, including 3 catastrophic APS); 3 were fatal. The rate of TEs was 8.1% in the SLE or lupus without APAs group, 22.2% in the SLE or lupus with APAs group and 50% in the APS group. In 12 patients, TPO‐RAs were continued after TE onset, combined with an anticoagulant (<jats:italic>n</jats:italic> = 12) and/or an antiplatelet agent (<jats:italic>n</jats:italic> = 3). Only one TE relapse occurred in the nine patients with TPO‐RAs maintained and combined with an anticoagulant after TE. TPO‐RAs may be effective safe in ITP associated with SLE and no APAs. Their use should be carefully considered in the presence of thrombotic risk factors and/or APA positivity and should be avoided in patients with definite APS. When a TE occurs, risk of relapse is low with maintenance of the TPO‐RA combined with anticoagulation.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"9 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic Hematopoietic Stem Cell Transplantation in Adolescents and Young Adults With Acute Lymphoblastic Leukemia—A Retrospective, Dual-Center Study","authors":"Oren Pasvolsky, Shai Shimony, Rima M. Saliba, Curtis Marcoux, Celina Ledesma, Gabriela Rondon, Priti Tewari, Dristhi Ragoonanan, Nicholas J. Short, Elias Jabbour, Mahasweta Gooptu, Vincent T. Ho, Robert J. Soiffer, Joseph H. Antin, John Koreth, Corey S. Cutler, Jonathan D. Paolino, Christine N. Duncan, Leslie E. Lehmann, Daniel J. DeAngelo, Nitin Jain, Richard Champlin, Elizabeth Shpall, Marlise R. Luskin, Partow Kebriaei","doi":"10.1002/ajh.70101","DOIUrl":"https://doi.org/10.1002/ajh.70101","url":null,"abstract":"Survival outcomes for adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) have improved with modern frontline therapies and minimal residual disease (MRD)-guided strategies. As a result, allogeneic hematopoietic cell transplantation (HCT) is increasingly deferred in first remission (CR1) and used in the relapsed setting. However, data on HCT outcomes in second remission (CR2) remain limited in AYAs. We conducted a dual-center retrospective study of AYA patients aged 15–40 years who underwent HCT in CR2 between 2010 and 2022. Among 164 patients, the median age was 25 years; 66% were male and 80% had B-ALL. Frontline therapies included pediatric-inspired (54%) and hyperCVAD-based (33%) regimens. Most received myeloablative conditioning (74%), and 67% were MRD-negative at HCT. At a median follow-up of 36 months, 3-year overall survival (OS) and progression-free survival (PFS) were 53% and 46%. The 3-year cumulative incidences of relapse and non-relapse mortality were 36% and 18%, respectively. The 6-month incidence of grade 2–4 acute graft-versus-host disease (GVHD) was 36%, and grade 3–4 was 14%. Chronic GVHD occurred in 27% at 3 years, with 37% moderate and 25% severe. On multivariable analysis, a HCT-specific comorbidity index &gt; 3 was independently associated with inferior OS, PFS, and higher non-relapse mortality. MRD positivity predicted worse PFS and higher relapse risk but not OS. These findings support HCT in CR2 as a curative option for AYA patients with ALL. Outcomes are influenced by MRD status and comorbidities, underscoring the need for risk-adapted transplant strategies.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"108 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characteristics, Treatment Responses and Outcomes of Light Chain Multiple Myeloma","authors":"Abiola Bolarinwa, Saurabh Zanwar, Nadine Abdallah, Francis K. Buadi, Suzanne R. Hayman, Morie A. Gertz, Angela Dispenzieri, Eli Muchtar, Prashant Kapoor, Wilson Gonsalves, Taxiarchis Kourelis, David Dingli, Rahma Warsame, Nelson Leung, Joselle Cook, Moritz Binder, Yi Lin, Yi Hwa, Michelle G. Rogers, Miriam Hobbs, Amie Fonder, Dragan Jevremovic, S. Vincent Rajkumar, Shaji K. Kumar","doi":"10.1002/ajh.70099","DOIUrl":"https://doi.org/10.1002/ajh.70099","url":null,"abstract":"Light chain multiple myeloma (LCMM) is a subtype of multiple myeloma (MM) characterized by the exclusive production of immunoglobulin light chains and accounts for 15%–20% of newly diagnosed MM. A comprehensive comparison of LCMM with MM producing intact immunoglobulin (non‐LCMM) remains limited. In this retrospective study, we described distinct clinical and cytogenetic features and assessed long‐term outcomes in 852 LCMM patients diagnosed between 01/01/2004 and 12/31/2022, compared with non‐LCMM controls matched for age, sex, and year of diagnosis. On univariable analysis, LCMM patients were more likely to present with elevated creatinine (&gt; 2 mg/dL), beta‐2‐microglobulin ≥ 5.5 mg/L, elevated LDH, hypercalcemia, t(11;14), del(13q), and t(6;14). Conversely, IMS‐IMWG high‐risk disease, hyperdiploidy, t(4;14), and serum albumin &lt; 3.5 g/dL were less common. On multivariable analysis, elevated creatinine (OR: 5.1, 95% CI: 1.2–27, <jats:italic>p</jats:italic> = 0.04), t(11;14) (OR: 2.6, 95% CI: 1.3–5.2, <jats:italic>p</jats:italic> = 0.006), and del(13q) (OR: 4.1, 95% CI: 2.1–8.2, <jats:italic>p</jats:italic> &lt; 0.001) were independently associated with LCMM, while IMS‐IMWG high‐risk disease (OR: 0.3, 95% CI: 0.1–0.8, <jats:italic>p</jats:italic> = 0.02) and hyperdiploidy (OR: 0.3, 95% CI: 0.1–0.7, <jats:italic>p</jats:italic> = 0.002) were less frequent. Despite these differences, progression‐free survival with frontline treatment (HR: 0.97, 95% CI: 0.84–1.11, <jats:italic>p</jats:italic> = 0.63) and overall survival (HR: 0.99, 95% CI: 0.87–1.13, <jats:italic>p</jats:italic> = 0.94) were similar between LCMM and non‐LCMM patients. This study highlights the distinct clinical and cytogenetic features of LCMM, marked by higher rates of renal failure, t(11;14), and del(13q), lower prevalence of IMS‐IMWG high‐risk disease, and comparable survival outcomes.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"28 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TEG and ROTEM: Technology and Clinical Applications, 2026 Update","authors":"Mckenna M. Longacre, Juan C. Ibla","doi":"10.1002/ajh.70074","DOIUrl":"https://doi.org/10.1002/ajh.70074","url":null,"abstract":"Viscoelastic testing (VET) has evolved significantly since its inception in the mid‐20th century, when it was first developed to guide transfusion strategies in trauma and surgical patients. Initially, VET technologies such as TEG and ROTEM assessed clot formation by measuring the mechanical resistance of a pin or piston within a blood sample. Recent advances have introduced automated, cartridge‐based systems and novel detection methods—including resonance frequency and ultrasound‐based sonorheometry—these new systems allow for more precise, rapid, and user‐friendly assessment of clot dynamics at the point of care. VET is now indicated for a wide range of clinical scenarios where complex coagulopathy is anticipated, including trauma, cardiac surgery, liver transplantation, obstetric hemorrhage, and hematologic disorders such as DIC. Its use is expanding into new populations, including pediatric cardiac surgery, patients with inflammatory bowel disease, and those with COVID‐19. However, VET remains limited in its ability to reliably detect therapeutic anticoagulants and certain congenital bleeding disorders, such as von Willebrand disease and deficiencies of protein C, S, and antithrombin. Technical limitations, including potential discrepancies between in vitro and in vivo clot formation, and lack of FDA approval for pediatric use have imposed implementation barriers to centers interested in pediatric VET. Looking forward, the integration of VET data with electronic medical records, the development of predictive models, artificial intelligence, and continued innovation in platelet function assessment and detection technologies are poised to enhance the clinical utility of VET. As guidelines and evidence continue to evolve, VET is positioned to become an increasingly important tool for real‐time, individualized management of coagulopathy in diverse patient populations.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"13 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of Concurrent (Double‐Positive) JAK2, CALR, or MPL Mutations and Corresponding Clinicopathologic Features: Analysis of 21556 Mayo Clinic NGS Studies Including 2651 Informative Cases","authors":"Rong He, Paul L. Ollila, Xi Zhang, Ji Yuan, Min Shi, Aruna Rangan, Naseema Gangat, Dong Chen, Ayalew Tefferi, David S. Viswanatha","doi":"10.1002/ajh.70098","DOIUrl":"https://doi.org/10.1002/ajh.70098","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"74 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying Morbidity Risk Attributed to Red-Cell Transfusion Volume in Optimally Transfused Patients With β-Thalassemia.","authors":"Khaled M Musallam,Angela Vitrano,Alessandro Inzerillo,Rosario Di Maggio,Rita Barone,Antonino Giangreco,Maria Concetta Renda,Emanuela Fecarotta,Antonio Troia,Antonino Giambona,Giovan Battista Ruffo,Efthymia Vlachaki,Theodora M Venou,Paolo Ricchi,Brunella Ziello,Marilena Serra,Elena Colizzi,Filomena Longo,Martina Culcasi,Aurelio Maggio","doi":"10.1002/ajh.70100","DOIUrl":"https://doi.org/10.1002/ajh.70100","url":null,"abstract":"In the long-term follow up study (de-LIGHT), the magnitude of transfusion burden was significantly and incrementally associated with morbidity development in transfusion-dependent patients achieving target hemoglobin thresholds.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"76 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline Pathogenic Variants in MUTYH Are Associated With Inferior Survival After Hematopoietic Cell Transplantation in Patients With Hematologic Malignancies or Disorders.","authors":"Maryam Rafati,Youjin Wang,Ashwin L Koppayi,Sharon A Savage,Lucy A Godley,Kirsten M Williams,Christopher Porter,Kristine Jones,Belynda Hicks,Stephen R Spellman,Meilun He,Rasha Atshan,Caidon Iwuagwu,Yung-Tsi Bolon,Esteban Arrieta-Bolaños,Jennifer N Saultz,Cara L Benjamin,Stephanie J Lee,Wael Saber,Shahinaz M Gadalla","doi":"10.1002/ajh.70093","DOIUrl":"https://doi.org/10.1002/ajh.70093","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"14 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypomethylating Therapy With or Without Eltrombopag in Elderly Patients With Acute Myeloid Leukemia: Results From the Randomized, Placebo‐Controlled Phase 2 DELTA Trial","authors":"Katja Sockel, Christoph Röllig, Anke Mütherig, Martina Crysandt, Sven Zukunft, Regina Herbst, Richard Noppeney, Kerstin Schäfer‐Eckardt, Martin Kaufmann, Uta Oelschlaegel, Frank Fiebig, Aristoteles Giagounides, Katharina Götze, Sebastian Scholl, Andreas Lück, Kathrin Rieger, Thomas Geer, Philipp Kiewe, Carsten Müller‐Tidow, Hubert Serve, Claudia D. Baldus, Ulrich Kaiser, Stefan Mahlmann, Burkhard Schmidt, Stefani Parmentier, Thomas Illmer, Ruth Seggewiss‐Bernhardt, Alexander Kiani, Hartmut Linde, Heinz Dürk, Michael Kramer, Desiree Kunadt, Katharina Schmidt‐Brücken, Ekaterina Balaian, Karolin Trautmann‐Grill, Leo Ruhnke, Jan Moritz Middeke, Malte von Bonin, Gerhard Ehninger, Christian Thiede, Martin Bornhäuser, Johannes Schetelig, Uwe Platzbecker","doi":"10.1002/ajh.70091","DOIUrl":"https://doi.org/10.1002/ajh.70091","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"37 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Algorithm for Estimating the Likelihood of Venous Thromboembolism in Primary Care Using Structured and Unstructured Electronic Health Record Data.","authors":"Siona Prasad,Patricia C Dykes,Richard Schreiber,Shadi Hijjawi,Khalid Nawab,Alice Kim,Stuart Lipsitz,Ania Syrowatka,Lipika Samal,David W Bates,Veysel Karani Baris,Tien Thai,Michael Sainlaire,Frank Y Chang,John Novoa-Laurentiev,Gregory Piazza,Wenyu Song","doi":"10.1002/ajh.70096","DOIUrl":"https://doi.org/10.1002/ajh.70096","url":null,"abstract":"Venous thromboembolism (VTE) is a major public health concern. It is often clinically difficult to diagnose and affects up to 900 000 individuals annually in the United States. Delayed or missed VTE diagnosis can impact treatment and increase morbidity and mortality. This retrospective study utilized structured and unstructured electronic health record (EHR) data from a large integrated care network in the northeastern US, focusing on 4678 adult patients presenting with at least one VTE-associated sign or symptom at primary care visits during 2019-2020. Feature selection incorporated expert-guided and data-driven approaches, resulting in a final set of demographic, clinical history, and sign/symptom risk factors. The primary analysis developed seven machine learning models to predict VTE incidence. Secondary analyses included the prediction of timely and delayed VTE diagnoses. All models showed predictive ability with area under the curve (AUC) of 0.83-0.88. The logistic regression model demonstrated robust performance in predicting incident VTE cases, achieving an AUC of 0.88 (95% CI: 0.86-0.90). Multiple risk factors were identified, including cancer history, smoking history, and spinal cord trauma. Variations in the top risk factors between timely and delayed prediction models highlighted how certain patients were more likely to have a delayed or missed diagnosis. This study highlights the potential for data-driven tools to facilitate timely, point-of-care VTE detection by leveraging structured and unstructured EHR data. The prediction model accurately estimated the likelihood of incident VTEs, especially in cases diagnosed late, showing potential to reduce costly diagnostic delays.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"41 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}