HemaSphere最新文献

{"title":"Comparable outcomes for pediatric acute lymphoblastic leukemia patients receiving conditioning with total body irradiation or chemotherapy: A nationwide, Korean registry-based study","authors":"Kyung Taek Hong,&nbsp;Jung Yoon Choi,&nbsp;Hyery Kim,&nbsp;Ho Joon Im,&nbsp;Seung Min Hahn,&nbsp;Chuhl Joo Lyu,&nbsp;Hee Young Ju,&nbsp;Keon Hee Yoo,&nbsp;Eu Jeen Yang,&nbsp;Sung-Soo Yoon,&nbsp;Hyeon Jin Park,&nbsp;Hyoung Soo Choi,&nbsp;Hee Won Chueh,&nbsp;Deok-Hwan Yang,&nbsp;Joon Ho Moon,&nbsp;Jae Min Lee,&nbsp;Jung-Hee Lee,&nbsp;Jeong-A Kim,&nbsp;Jong-Ho Won,&nbsp;Hyoung Jin Kang","doi":"10.1002/hem3.70158","DOIUrl":"https://doi.org/10.1002/hem3.70158","url":null,"abstract":"<p>Acute lymphoblastic leukemia (ALL) is the predominant malignancy in pediatric patients, and allogeneic hematopoietic stem cell transplantation (HSCT) plays a critical role in high-risk cases. However, real-world nationwide data comparing the outcomes of conditioning regimens are limited. This nationwide registry-based study analyzed data from 270 Korean pediatric patients with high-risk or relapsed ALL who underwent their first allogeneic HSCT with myeloablative conditioning. Among all analyzed patients, 118 received total body irradiation-based conditioning (MAC-TBI) and 152 received chemotherapy-based conditioning (MAC-Chemotherapy), of whom 96.6% underwent busulfan-based regimens. MAC-TBI recipients were older at diagnosis and at HSCT. No significant differences were observed between groups in neutrophil or platelet engraftment times, or infused CD34+ cell doses. Acute graft-versus-host disease (GVHD) incidences (grades II–IV and III–IV) were comparable, although chronic GVHD incidence tended to be lower in the MAC-Chemotherapy group (21.0% vs. 31.1%, P = 0.072). Additionally, the 5-year event-free survival (EFS) rates for MAC-TBI versus MAC-Chemotherapy were 73.7% and 69.8% (P = 0.827), respectively; the 5-year overall survival (OS) rates were 76.3% and 80.2% (P = 0.941), respectively, indicating that conditioning regimen did not significantly impact survival. Pediatric disease risk index, recent HSCT era, haploidentical donor type, and pre-transplant disease status independently influenced EFS and OS, whereas anti-thymocyte globulin administration significantly improved moderate-to-severe chronic GVHD, leukemia-free survival. This nationwide real-world analysis demonstrated comparable outcomes between myeloablative TBI-based and chemotherapy-based conditioning regimens in pediatric patients with ALL. These findings may inform the development of improved treatment strategies for this patient population.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 6","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the secret life of the spleen in sickle cell disease","authors":"Adama Ladu,&nbsp;Stephen P. Hibbs","doi":"10.1002/hem3.70157","DOIUrl":"https://doi.org/10.1002/hem3.70157","url":null,"abstract":"&lt;p&gt;The spleen is a complex and often misunderstood organ, particularly in the context of sickle cell disease (SCD). Although hyposplenism is commonly observed in SCD, it can paradoxically coexist with features of hypersplenism, splenomegaly, and acute splenic sequestration. This apparent contradiction demonstrates the multifaceted nature of splenic function, where different physiological roles may be variably affected by disease. If clinicians could accurately measure splenic function and correlate clinical outcomes in SCD, it could facilitate risk-adapted approaches to infection prophylaxis – and potentially other complications linked to splenic dysfunction.&lt;/p&gt;&lt;p&gt;In this article, we survey both the established and emerging roles of the spleen and current methods of assessing splenic function. We then discuss why these assessments could be valuable in the management of SCD, particularly in resource-constrained settings, and review the predictive value of current tools.&lt;/p&gt;&lt;p&gt;The spleen is the largest organ of the lymphatic system and plays an important role in both immune defense and regulation of blood cell quality. One of its primary functions is the phagocytic filtration of the bloodstream, enabling the clearance of pathogens and cellular debris. It also contributes to adaptive immunity through the production of opsonising antibodies, which are particularly important for eliminating encapsulated bacteria (e.g., &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt;) and intracellular parasites (e.g., &lt;i&gt;Plasmodium falciparum&lt;/i&gt;, &lt;i&gt;Babesia&lt;/i&gt; spp).&lt;/p&gt;&lt;p&gt;Beyond an immune role, the spleen contributes to maintaining the quality of circulating red cells. It removes senescent erythrocytes from the bloodstream and recycles their iron for reuse in erythropoiesis. This filtration function may help explain the association between hyposplenism and vascular complications, such as the increased incidence of thrombotic events observed after splenectomy. The spleen also acts as a physiological reservoir, storing extra blood to release in times of increased demand, such as severe blood loss or intense physical exertion. A striking example of this reservoir function is observed in the Bajau people – commonly known as “sea nomads” – who have markedly enlarged spleens that enable them to dive to depths of up to 200 feet and remain underwater for as long as 13 minutes.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Emerging research has revealed that the spleen engages in bidirectional communication with other organs.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; A notable example is the gut–spleen axis, in which the gut microbiota modulates splenic immune activity, while splenic cytokines reciprocally influence bowel inflammation. Interventions such as probiotics, dietary modification, and fecal microbiota transplantation are under investigation for their potential to modulate this gut-spleen interaction.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Several modalities can be employed to evaluate splenic function,&lt;span&gt;&lt;sup&gt;4&lt;/sup","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 6","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of PET/CT for CAR T cell therapy in relapsed/refractory multiple myeloma","authors":"Patrick Born,&nbsp;David Fandrei,&nbsp;Song Yau Wang,&nbsp;Carmen Perez-Fernandez,&nbsp;Luise Fischer,&nbsp;Jule Ussmann,&nbsp;Enrica Bach,&nbsp;Sandra Hoffmann,&nbsp;Klaus H. Metzeler,&nbsp;Marco Herling,&nbsp;Carmen Herling,&nbsp;Madlen Jentzsch,&nbsp;Andreas Boldt,&nbsp;Sabine Seiffert,&nbsp;Ronny Baber,&nbsp;Heike Weidner,&nbsp;Georg-Nikolaus Franke,&nbsp;Timm Denecke,&nbsp;Osama Sabri,&nbsp;Uwe Platzbecker,&nbsp;Vladan Vucinic,&nbsp;Hans Jonas Meyer,&nbsp;Lars Kurch,&nbsp;Maximilian Merz","doi":"10.1002/hem3.70159","DOIUrl":"https://doi.org/10.1002/hem3.70159","url":null,"abstract":"<p>PET/CT plays an important role in staging of multiple myeloma (MM) and detecting extramedullary disease (EMD); however, its role in patients treated with commercially available CAR T cell therapies is unclear. We evaluated 61 patients treated with CAR T cell products. In 53 patients, PET/CT was available before CAR T infusion, and 43 had follow-up PET/CT on day 30. Findings from PET/CT were correlated to (CAR) T single-cell dynamics, fitness and T cell receptor diversity after infusion, and serological markers of tumor burden and inflammation. Patients with bone-independent EMD had inferior median progression-free survival (PFS: 3 vs. 15 months, <i>p</i> = 0.01). Univariate and multivariate analysis showed that EMD but not the number of lesions or metabolic tumor volume (MTV) were associated with inferior PFS. High MTV was connected to higher baseline sBCMA and Interleukin-6 levels, but not associated with hampered CAR T cell expansion or decreased fitness of the bystander T cell compartment. Follow-up PET/CTs identified patients with metabolic complete remissions, which were associated with better PFS. PET/CT identifies patients with high risk of relapse after CAR T cell therapy.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 6","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plenary Abstracts Session & Oral Presentations","authors":"","doi":"10.1002/hem3.70151","DOIUrl":"https://doi.org/10.1002/hem3.70151","url":null,"abstract":"","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 S1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster Sessions","authors":"","doi":"10.1002/hem3.70152","DOIUrl":"https://doi.org/10.1002/hem3.70152","url":null,"abstract":"","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 S1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Publication Only","authors":"","doi":"10.1002/hem3.70153","DOIUrl":"https://doi.org/10.1002/hem3.70153","url":null,"abstract":"","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 S1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the phenotypic and genetic landscape of congenital neutropenia through whole-exome and genome sequencing","authors":"Séverine Marti,&nbsp;Philippe Pellet,&nbsp;Blandine Beaupain,&nbsp;Léa Durix,&nbsp;Julien Buratti,&nbsp;Yves Réguerre,&nbsp;Nathalie Aladjidi,&nbsp;Saba Azarnoush,&nbsp;Severine Clauin,&nbsp;Wahid Abou Chahla,&nbsp;Gilles Blaison,&nbsp;Jeremy Bertand,&nbsp;Damien Bodet,&nbsp;Benoit Brethon,&nbsp;Jessica Chane-Teng,&nbsp;Manon Delafoy,&nbsp;Chrystelle Dupraz,&nbsp;Virginie Gandemer,&nbsp;Philippe Denizeau,&nbsp;Alice Goldenberg,&nbsp;Pierre Hirsch,&nbsp;Anaïs l'Haridon,&nbsp;Aude Marie-Cardine,&nbsp;Gabriella Vera,&nbsp;Brigitte Nelken,&nbsp;Laure Nizery,&nbsp;Marie Nolla,&nbsp;Marlène Pasquet,&nbsp;Jérémie Rosain,&nbsp;Louis Terriou,&nbsp;Isabelle Plo,&nbsp;Jean Donadieu,&nbsp;Christine Bellanné-Chantelot","doi":"10.1002/hem3.70150","DOIUrl":"https://doi.org/10.1002/hem3.70150","url":null,"abstract":"<p>Congenital neutropenia (CN) comprises a heterogeneous group of rare genetic disorders. While some CN cases present only with neutropenia, others present with additional extra-hematological manifestations. The most common cause of CN is variants in <i>ELANE</i>; however, approximately 30 other genes have been implicated. Despite this, the genetic basis remains unknown in roughly 30% of cases. The clinical and genetic heterogeneity of CN makes diagnosis particularly challenging. To address this, we conducted exome or genome sequencing of 60 patients with a suspected diagnosis of CN that remained unresolved following targeted sequencing. A genetic diagnosis was established in 25 patients (42%). Variants were identified in 15 different genes. Half of these cases involved genes traditionally associated with hereditary immunodeficiencies (<i>GINS4</i>, <i>CARD11</i>, <i>ADA2</i>, <i>GINS1</i>, <i>LCP1</i>, <i>SASH3</i>, and <i>WAS</i>). One-third of the cases carried variants in genes linked to syndromic disorders (<i>VPS13B</i>, <i>TAFAZZIN</i>, <i>CLPB</i>, and <i>TONSL</i>), demonstrating variable penetrance of extra-hematological phenotypes. A smaller subset (15%) harbored variants in genes associated with inherited bone marrow failure syndromes (<i>BLM</i>, <i>RPL18</i>, <i>SAMD9</i>, and <i>SRP72</i>), identified incidentally due to atypical presentations. Compared to patients with ELANE-CN, these individuals were diagnosed later, had fewer severe bacterial infections and gingivitis, exhibited less profound neutropenia, lacked monocytosis, and had a granulocytic maturation arrest, often beyond the promyelocytic stage. A shared feature among these cases was a tendency toward reduced lymphocyte subsets, particularly NK cells. This study highlights the significant contribution of exome and genome sequencing in diagnosing CN, given the phenotypic overlap, genetic heterogeneity, and variable penetrance of immunological and extra-hematological features.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 6","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of myeloid neoplasia associated with prolonged immune cell-associated hematotoxicity after CAR T-cell treatment of B-cell lymphoma: Should we surveille for pre-existing myeloid mutations?","authors":"Mattias Carlsten,&nbsp;Elisa Linnea Lindfors Rossi,&nbsp;Martin Jädersten,&nbsp;Bianca Tesi,&nbsp;Sulaf Abd Own,&nbsp;Brigitta Sander,&nbsp;Stefan Deneberg,&nbsp;Anne Ivinskiy,&nbsp;Kristina Sonnevi,&nbsp;Hanna Sjölund,&nbsp;Gunilla Enblad,&nbsp;Björn Wahlin,&nbsp;Stephan Mielke","doi":"10.1002/hem3.70160","DOIUrl":"https://doi.org/10.1002/hem3.70160","url":null,"abstract":"&lt;p&gt;Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the outcome of patients with B-cell malignancies as recently exemplified by the Swedish cohort.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Although the development of secondary cancers such as T-cell lymphomas following viral transduction has been a major concern from the very beginning,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; relatively few such cases have been reported. Instead, there is accumulating evidence that myeloid malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) can occur in up to 5%–7% of patients, which, together with a smaller proportion of other secondary malignancies, constitutes the second most common cause of non-relapse mortality after CAR T-cell therapy.&lt;span&gt;&lt;sup&gt;3-6&lt;/sup&gt;&lt;/span&gt; However, so far, we do not understand the biology behind therapy-related myeloid neoplasia (tMN), nor can we predict who is at risk. To better understand this, we have launched an ex vivo correlative study (Ethical Review Board Dnr 2021-04692) to which we enroll our patients undergoing CAR T-cell treatment.&lt;/p&gt;&lt;p&gt;In this study, we present two patients with B-cell lymphoma who developed tMN after receiving CD19-directed CAR T-cell therapy that triggered long-lasting immune effector cell-associated hematotoxicity (ICAHT)&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; (Table 1 and Figure 1). Both patients were males diagnosed with follicular lymphoma (FL) for which they received Rituximab–Bendamustine as the first line. Both patients transformed to large B-cell lymphoma (LBCL) and were primary refractory to Obinutuzumab–Cyclophosphamide–Vincristine–Doxorubicine–Dexamethasone (HyperCVAD), therefore qualifying for CAR T-cell therapy with Axi-cel as standard of care. Patient A received bridging therapy with Ifosfamide–Carboplatin–Etoposide (ICE) combined with radiotherapy, and patient B received Rituximab–Gemcitabine–Oxaliplatin (GemOx), resulting in a partial response in both cases. Axi-cel was administrated after lymphodepletion with Fludarabine and Cyclophosphamide. Patient A had no CRS or ICANS, while patient B developed a grade I CRS and received Tocilizumab. The course of treatment for each patient is summarized in Figure 1.&lt;/p&gt;&lt;p&gt;After cell infusion, patient A developed early ICAHT grade III that resulted in primary aplastic bone marrow while patient B developed biphasic ICAHT grade III in both its early and late stages. Both patients were promptly treated with G-CSF with suboptimal responses. The schedules for G-CSF administration slightly differed between the patients; while patient A was treated with 1-3 doses/week, patient B received 1-2 doses/week. The CAR/Hematotox&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; score was retrospectively calculated for both patients and determined high, underscoring the relevance of this tool on predicting later complications. In particular patient B was allocated to the same group even if lacking ferritin levels since a total score of 5 was achieved. Of note, patient A had several CM","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 6","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of erythroid-stimulating agent and luspatercept in VEXAS syndrome: A multicenter retrospective study by the FRENVEX group","authors":"Maël Heiblig,&nbsp;Vincent Jachiet,&nbsp;Jérôme Hadjadj,&nbsp;Lin Pierre Zhao,&nbsp;Thibault Comont,&nbsp;Hervé Lobbes,&nbsp;Valentin Lacombe,&nbsp;Anne Blandine Boutin,&nbsp;Joris Galland,&nbsp;Benjamin Terrier,&nbsp;Sophie Georgin-Lavialle,&nbsp;Pierre Fenaux,&nbsp;Arsène Mekinian,&nbsp;the FRENVEX Group","doi":"10.1002/hem3.70156","DOIUrl":"https://doi.org/10.1002/hem3.70156","url":null,"abstract":"&lt;p&gt;VEXAS syndrome (for Vacuoles in myeloid progenitors, E1 ubiquitin activating enzyme, X-linked, Autoinflammatory manifestations, and Somatic) is due to somatically acquired &lt;i&gt;UBA1&lt;/i&gt; mutations within hematopoietic stem/progenitor cells.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; It is characterized clinically by a variety of autoinflammatory manifestations and biologically by marked cytopenia and more specifically macrocytic anemia.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Anemia in VEXAS is usually non-regenerative and red blood cell (RBC) transfusion dependency is observed in 23%–83% of cases.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; Precise mechanisms underlying anemia in VEXAS are not completely elucidated. Chronic inflammation certainly contributes, as RBC transfusion independency (TI) might be reached by controlling inflammatory burden.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Besides RBC transfusion, there is no validated therapeutic option regarding anemia management. Erythroid-stimulating agents (ESA) and more recently luspatercept (LUSPA) have been approved for the treatment of anemia in MDS.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; The aim of this multicenter retrospective study was to evaluate erythroid response to those drugs (HI-E according to IWG-2018 criteria) in VEXAS patients with anemia treated with ESA and LUSPA.&lt;/p&gt;&lt;p&gt;Anemic (Hb&lt;10 g/dL) VEXAS patients, with or without MDS, who were treated with ESA and/or LUSPA between 2020 and 2024 in eight centers of the French Vexas (FRENVEX) group (Lyon Sud, Clermont-Ferrant, Toulouse, Paris Saint-Antoine, Paris Saint-Louis, Bourg-en-Bresse, Centre Alpes-Léman, and Angers)&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; were included. Definitions and responses criteria are defined in Supporting Information.&lt;/p&gt;&lt;p&gt;Overall, 45 VEXAS patients received ESA (&lt;i&gt;N&lt;/i&gt; = 26 darbepoietin, &lt;i&gt;N&lt;/i&gt; = 15 epoietin-alfa, &lt;i&gt;N&lt;/i&gt; = 3 epoietin-beta) as the first-line treatment, 8 of whom were switched to LUSPA after ESA failure. Regarding delay between &lt;i&gt;UBA1&lt;/i&gt; molecular diagnosis and ESA initiation, 33% (15/45) of patients started ESA before a formal VEXAS diagnosis (median time before diagnosis: 11.1 months) (95% CI: 0.95–85.1), while the others (30/45) initiated ESA with a median time of 6.6 months (95% CI: 0.31–121.1) after VEXAS diagnosis. Median age at ESA initiation was 73.3 (range: 49–87.7). Regarding &lt;i&gt;UBA1&lt;/i&gt; variants, 14 (31%), 14 (31%), 6 (13%), and 11 (24%) harbored p.Met41Thr, pMet41Leu, p.Met41Val, and alternative variants (seven splice, three S56, and one active adenylation domain) mutations, respectively (Figure S1A). Sixteen patients (35.5%) were non-RBC transfusion dependent (NTD), 13 (29%) had high transfusion burden (HTB), and 16 (35.5%) low TB (LTB) before ESA initiation according to IWG 2018 criteria. Clinical and biological characteristics of patients with and without RBC transfusion dependency were similar (Table S1). Thirty seven (82%) patients had associated MDS (IPSS-R/M characteristics are reported in Figure S1A). Detailed hematological features are reported i","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 6","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New horizons in the pharmacological management of venous thromboembolism","authors":"Andreas Verstraete,&nbsp;Quentin Van Thillo,&nbsp;Thomas Vanassche,&nbsp;Peter Verhamme","doi":"10.1002/hem3.70143","DOIUrl":"https://doi.org/10.1002/hem3.70143","url":null,"abstract":"<p>Many patients suffer from venous thromboembolism (VTE) and its consequences. Despite substantial advancements with the introduction of direct oral anticoagulants (DOACs), patients and clinicians still encounter challenges in the acute and long-term management of VTE, such as recurrent events, anticoagulant-related bleeding complications, and post-thrombotic symptoms. Additionally, certain patient populations, including those with advanced kidney failure and liver cirrhosis and elderly individuals, were excluded from phase 3 clinical DOAC trials. Therefore, the call for innovative anticoagulants in the acute and long-term management of VTE resonates, not only to mitigate long-term recurrences and post-thrombotic symptoms but also to maintain the delicate harmony of hemostasis. Novel targets within the coagulation and fibrinolytic system, as well as mechanisms governing adherence to the vessel wall, are currently being explored to address these unmet needs. First, factor XI inhibitors have shown promise in preclinical and phase 2 clinical studies to tackle thrombosis while preserving hemostasis, although phase 3 trials are required for confirmation. Next, there is interest to boost the endogenous fibrinolytic system, with α2-antiplasmin, thrombin-activatable fibrinolysis inhibitor, and plasminogen activator inhibitor-1 emerging as potential attractive targets. Finally, strategies to inhibit the interaction between leucocytes and the vessel wall are also under exploration. This review provides an overview of the latest clinical advancements in the pharmacological management of VTE.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 6","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}