HemaSphere最新文献

{"title":"Autologous stem cell transplantation versus consolidation chemotherapy as postremission treatment in newly diagnosed favorable- and intermediate-risk patients with AML: A comparative analysis of HOVON–SAKK–Nordic trials","authors":"Dimitrios Kotsos,&nbsp;Carin Hazenberg,&nbsp;Thomas Pabst,&nbsp;Patrycja Gradowska,&nbsp;Markus G. Manz,&nbsp;Johan Maertens,&nbsp;Carlos Graux,&nbsp;Marie-Christiane Vekemans,&nbsp;Bjorn T. Gjertsen,&nbsp;Sören Lehmann,&nbsp;Catharina H. M. J. Van Elssen,&nbsp;Peter J. M. Valk,&nbsp;Edo Vellenga,&nbsp;Gert Ossenkoppele,&nbsp;Bob Löwenberg,&nbsp;Marc H. G. P. Raaijmakers,&nbsp;Gerwin Huls,&nbsp;Jurjen Versluis","doi":"10.1002/hem3.70462","DOIUrl":"https://doi.org/10.1002/hem3.70462","url":null,"abstract":"<p>High-dose chemotherapy (CT), followed by autologous hematopoietic cell transplantation (auto-HCT) or consolidation CT, are postremission strategies for European LeukemiaNet 2022 (ELN2022) favorable- or intermediate-risk patients with acute myeloid leukemia (AML) in complete remission (CR) without measurable residual disease (MRD). We conducted a retrospective, nonrandomized analysis to compare the efficacy and safety of auto-HCT versus CT in newly diagnosed AML patients aged 18–65 years treated within two recent HOVON–SAKK–Nordic trials. From a total of 1005 patients with ELN2022 favorable- or intermediate-risk AML, 224 received busulfan/cyclophosphamide (Bu/Cy), followed by auto-HCT, and 199 received mitoxantrone/etoposide-based CT. The 5-year relapse-free survival (RFS) and overall survival (OS) were comparable between auto-HCT and CT (RFS: 60% vs. 56%, P = 0.70; OS: 72% vs. 71%, P = 0.76). In multivariable analysis, auto-HCT was not associated with a significant difference in RFS (HR 0.80, 95% CI 0.56–1.13, P = 0.20) or OS (HR 0.91, 95% CI 0.60–1.37, P = 0.64). Median time to platelet and neutrophil recovery was shorter with auto-HCT than CT (platelet: 42 vs. 57 days, neutrophil: 13 vs. 39 days). Subgroup analysis revealed that patients achieving CR after the second induction cycle or with baseline white blood cell counts &gt;20 × 10⁹/L had longer RFS with auto-HCT compared to CT (HR 0.17, P = 0.003 and HR 0.48, P = 0.02), which was not observed for OS. Focusing on ELN2022 favorable-risk patients (excluding <i>NPM1</i>mut MRD-positive) and MRD-negative intermediate-risk patients, RFS and OS were not different between consolidation strategies. Collectively, auto-HCT yielded similar RFS and OS to mitoxantrone/etoposide-based CT in favorable- and intermediate-risk AML, particularly in MRD-negative patients, with faster hematologic recovery.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785118","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":"Digital PCR-based non-invasive prenatal diagnosis should be considered in the evolving diagnostic pathway for sickle cell disease","authors":"Paloma Ropero,&nbsp;Fernando Ataúlfo González,&nbsp;Miguel Gómez,&nbsp;Jorge M. Nieto,&nbsp;Ana Villegas,&nbsp;Celina Benavente","doi":"10.1002/hem3.70446","DOIUrl":"https://doi.org/10.1002/hem3.70446","url":null,"abstract":"&lt;p&gt;We read with great interest the European Hematology Association (EHA) recommendations by de Montalembert et al. on preconceptual and antenatal screening and prenatal diagnosis for hemoglobinopathies. The manuscript provides a timely and valuable framework for genetic counseling and reproductive decision-making in thalassemia and sickle cell disease, particularly by emphasizing non-directive counseling and the need to adapt diagnostic strategies to local healthcare infrastructures.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;We would like to comment specifically on Question 4, concerning the laboratory tests that should be used for prenatal diagnosis. The authors appropriately state that invasive prenatal diagnosis based on chorionic villus sampling or amniocentesis remains the most established diagnostic approach, and they also highlight the current limitations of non-invasive prenatal testing (NIPT)/diagnosis for hemoglobinopathies. In particular, they cite previous data showing that the performance of non-invasive approaches for sickle cell disease has not yet reached that of invasive prenatal diagnosis.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;However, we believe that this section may benefit from a more explicit distinction in light of recent advances in non-invasive prenatal diagnosis (NIPD) based on cell-free fetal DNA and digital polymerase chain reaction (PCR). Our group has recently published a pilot study evaluating third-generation digital PCR for NIPD of sickle cell disease using relative mutation dosage analysis in maternal plasma. In this study, nine pregnant women carrying the HbS heterozygous variant were included. &lt;i&gt;Z&lt;/i&gt;-score classification correctly identified the fetal genotype in all conclusive cases, with one inconclusive result, and postnatal confirmation showed 100% concordance among classified cases.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In addition, our group is currently expanding this pilot experience in an ongoing prospective validation cohort that now includes 54 pregnant women. As the study is still ongoing, these data are not presented here; however, the expanded cohort underscores the feasibility of implementing this approach in a real-world diagnostic setting.&lt;/p&gt;&lt;p&gt;The published pilot findings are consistent with previous studies supporting the feasibility of cell-free DNA-based approaches for NIPD of hemoglobinopathies. Early work by Barrett et al. demonstrated the potential of digital PCR for non-invasive detection of sickle cell anemia, while van Campen et al. reported a targeted massively parallel sequencing approach for NIPD of fetal sickle cell disease.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; More recently, Shaw et al. developed a droplet digital PCR workflow based on relative mutation dosage for non-invasive fetal genotyping of maternal alleles, including a substantial cohort of sickle cell disease cases.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; In parallel, dPCR-based strategies have also shown promising results in beta-thalassemia, further supporting the growin","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783482","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":"Digital PCR-based non-invasive prenatal diagnosis should be considered in the evolving diagnostic pathway for sickle cell disease","authors":"Paloma Ropero,&nbsp;Fernando Ataúlfo González,&nbsp;Miguel Gómez,&nbsp;Jorge M. Nieto,&nbsp;Ana Villegas,&nbsp;Celina Benavente","doi":"10.1002/hem3.70446","DOIUrl":"https://doi.org/10.1002/hem3.70446","url":null,"abstract":"&lt;p&gt;We read with great interest the European Hematology Association (EHA) recommendations by de Montalembert et al. on preconceptual and antenatal screening and prenatal diagnosis for hemoglobinopathies. The manuscript provides a timely and valuable framework for genetic counseling and reproductive decision-making in thalassemia and sickle cell disease, particularly by emphasizing non-directive counseling and the need to adapt diagnostic strategies to local healthcare infrastructures.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;We would like to comment specifically on Question 4, concerning the laboratory tests that should be used for prenatal diagnosis. The authors appropriately state that invasive prenatal diagnosis based on chorionic villus sampling or amniocentesis remains the most established diagnostic approach, and they also highlight the current limitations of non-invasive prenatal testing (NIPT)/diagnosis for hemoglobinopathies. In particular, they cite previous data showing that the performance of non-invasive approaches for sickle cell disease has not yet reached that of invasive prenatal diagnosis.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;However, we believe that this section may benefit from a more explicit distinction in light of recent advances in non-invasive prenatal diagnosis (NIPD) based on cell-free fetal DNA and digital polymerase chain reaction (PCR). Our group has recently published a pilot study evaluating third-generation digital PCR for NIPD of sickle cell disease using relative mutation dosage analysis in maternal plasma. In this study, nine pregnant women carrying the HbS heterozygous variant were included. &lt;i&gt;Z&lt;/i&gt;-score classification correctly identified the fetal genotype in all conclusive cases, with one inconclusive result, and postnatal confirmation showed 100% concordance among classified cases.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In addition, our group is currently expanding this pilot experience in an ongoing prospective validation cohort that now includes 54 pregnant women. As the study is still ongoing, these data are not presented here; however, the expanded cohort underscores the feasibility of implementing this approach in a real-world diagnostic setting.&lt;/p&gt;&lt;p&gt;The published pilot findings are consistent with previous studies supporting the feasibility of cell-free DNA-based approaches for NIPD of hemoglobinopathies. Early work by Barrett et al. demonstrated the potential of digital PCR for non-invasive detection of sickle cell anemia, while van Campen et al. reported a targeted massively parallel sequencing approach for NIPD of fetal sickle cell disease.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; More recently, Shaw et al. developed a droplet digital PCR workflow based on relative mutation dosage for non-invasive fetal genotyping of maternal alleles, including a substantial cohort of sickle cell disease cases.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; In parallel, dPCR-based strategies have also shown promising results in beta-thalassemia, further supporting the growin","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785117","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":"Anti-BCMA immunotherapies deplete plasmacytoid dendritic cells and impair antiviral immunity in multiple myeloma","authors":"Ondrej Venglar,&nbsp;Eva Radova,&nbsp;Maxima Warmuzova,&nbsp;Daniel Bilek,&nbsp;Marketa Kudelkova,&nbsp;Katerina Jasinkova,&nbsp;Ludmila Muronova,&nbsp;Lucie Broskevicova,&nbsp;Veronika Kapustova,&nbsp;Jan Vrana,&nbsp;Tereza Novakova,&nbsp;Katerina Karasova,&nbsp;Michaela Hornakova,&nbsp;Tereza Popkova,&nbsp;Jana Mihalyova,&nbsp;Hana Plonkova,&nbsp;Michal Simicek,&nbsp;Jakub Radocha,&nbsp;Tereza Sevcikova,&nbsp;David Zihala,&nbsp;Juli Bago,&nbsp;Roman Hajek,&nbsp;Tomas Jelinek","doi":"10.1002/hem3.70455","DOIUrl":"https://doi.org/10.1002/hem3.70455","url":null,"abstract":"&lt;p&gt;Modern T-cell redirecting immunotherapy targeting B-cell maturation antigen (BCMA) and G protein–coupled receptor class C group 5 member D (GPRC5D) on malignant plasma cells (PCs) demonstrated remarkable efficacy in multiple myeloma (MM). Currently, approved therapies include bispecific antibodies (bsAbs) directed against BCMA—teclistamab (tec), elranatamab (elra), linvoseltamab, and against GPRC5D—talquetamab (tal),&lt;span&gt;&lt;sup&gt;1-4&lt;/sup&gt;&lt;/span&gt; as well as chimeric antigen receptor (CAR)-T cells targeting BCMA—ide-cel and cilta-cel.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; Infections remain the most common and critical complication associated with their use, including severe and fatal cases. This increased risk is driven by a combination of factors, including T-cell exhaustion, neutropenia, lymphopenia, and hypogammaglobulinemia. The use of combination regimens may further increase the risk of infection.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; In this context, targeting BCMA was associated with significantly higher infection risk compared to GPRC5D due to on-target off-tumor killing of PCs and B cells.&lt;span&gt;&lt;sup&gt;7-9&lt;/sup&gt;&lt;/span&gt; In addition, viral infections represent a substantial proportion of overall infectious burden with their true incidence being probably underestimated by current standard of infection reporting.&lt;span&gt;&lt;sup&gt;10-12&lt;/sup&gt;&lt;/span&gt; Respiratory viral infections are frequent, dominantly low-grade complications, often recurring or persisting, that considerably impair the quality of life of MM patients and may serve as an initial trigger for more severe bacterial superinfections. Interestingly, breakthrough infections remain common despite the use of multiple anti-infective and prophylactic measures, including immunoglobulin replacement therapy,&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; suggesting that additional unidentified mechanism may contribute to infection onset.&lt;/p&gt;&lt;p&gt;Among the primary immune components engaged in antiviral defense, dendritic cells (DCs) serve as essential co-activators and professional antigen-presenting cells (APCs). Although plasmacytoid DCs (pDCs) are less efficient APCs than myeloid/conventional dendritic cells (mDCs/cDCs), they play a central role in immune system activation against viruses through enormous Type I interferon (IFN) production, particularly IFN-α and IFN-β, following toll-like receptors (TLR7 and TLR9) engagement by viral nucleic acids.&lt;span&gt;&lt;sup&gt;13&lt;/sup&gt;&lt;/span&gt; Notably, BCMA expression in pDCs was first reported as early as 2017.&lt;span&gt;&lt;sup&gt;14&lt;/sup&gt;&lt;/span&gt; Here, we investigated whether anti-BCMA immunotherapy, including bsAbs and CAR-T cells, contributes to increased viral susceptibility by affecting the pDC compartment in MM patients.&lt;/p&gt;&lt;p&gt;Overall, 388 unique samples from 72 MM patients were assessed in this study in multiple cohorts (Table S1). Patient characteristics are summarized in Tables S2–S5. BCMA gene expression was analyzed using publicly available single-cell RNA sequencing (scRNA-seq) datasets from healthy donor (HD) b","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783880","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":"Anti-BCMA immunotherapies deplete plasmacytoid dendritic cells and impair antiviral immunity in multiple myeloma","authors":"Ondrej Venglar,&nbsp;Eva Radova,&nbsp;Maxima Warmuzova,&nbsp;Daniel Bilek,&nbsp;Marketa Kudelkova,&nbsp;Katerina Jasinkova,&nbsp;Ludmila Muronova,&nbsp;Lucie Broskevicova,&nbsp;Veronika Kapustova,&nbsp;Jan Vrana,&nbsp;Tereza Novakova,&nbsp;Katerina Karasova,&nbsp;Michaela Hornakova,&nbsp;Tereza Popkova,&nbsp;Jana Mihalyova,&nbsp;Hana Plonkova,&nbsp;Michal Simicek,&nbsp;Jakub Radocha,&nbsp;Tereza Sevcikova,&nbsp;David Zihala,&nbsp;Juli Bago,&nbsp;Roman Hajek,&nbsp;Tomas Jelinek","doi":"10.1002/hem3.70455","DOIUrl":"https://doi.org/10.1002/hem3.70455","url":null,"abstract":"&lt;p&gt;Modern T-cell redirecting immunotherapy targeting B-cell maturation antigen (BCMA) and G protein–coupled receptor class C group 5 member D (GPRC5D) on malignant plasma cells (PCs) demonstrated remarkable efficacy in multiple myeloma (MM). Currently, approved therapies include bispecific antibodies (bsAbs) directed against BCMA—teclistamab (tec), elranatamab (elra), linvoseltamab, and against GPRC5D—talquetamab (tal),&lt;span&gt;&lt;sup&gt;1-4&lt;/sup&gt;&lt;/span&gt; as well as chimeric antigen receptor (CAR)-T cells targeting BCMA—ide-cel and cilta-cel.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; Infections remain the most common and critical complication associated with their use, including severe and fatal cases. This increased risk is driven by a combination of factors, including T-cell exhaustion, neutropenia, lymphopenia, and hypogammaglobulinemia. The use of combination regimens may further increase the risk of infection.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; In this context, targeting BCMA was associated with significantly higher infection risk compared to GPRC5D due to on-target off-tumor killing of PCs and B cells.&lt;span&gt;&lt;sup&gt;7-9&lt;/sup&gt;&lt;/span&gt; In addition, viral infections represent a substantial proportion of overall infectious burden with their true incidence being probably underestimated by current standard of infection reporting.&lt;span&gt;&lt;sup&gt;10-12&lt;/sup&gt;&lt;/span&gt; Respiratory viral infections are frequent, dominantly low-grade complications, often recurring or persisting, that considerably impair the quality of life of MM patients and may serve as an initial trigger for more severe bacterial superinfections. Interestingly, breakthrough infections remain common despite the use of multiple anti-infective and prophylactic measures, including immunoglobulin replacement therapy,&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; suggesting that additional unidentified mechanism may contribute to infection onset.&lt;/p&gt;&lt;p&gt;Among the primary immune components engaged in antiviral defense, dendritic cells (DCs) serve as essential co-activators and professional antigen-presenting cells (APCs). Although plasmacytoid DCs (pDCs) are less efficient APCs than myeloid/conventional dendritic cells (mDCs/cDCs), they play a central role in immune system activation against viruses through enormous Type I interferon (IFN) production, particularly IFN-α and IFN-β, following toll-like receptors (TLR7 and TLR9) engagement by viral nucleic acids.&lt;span&gt;&lt;sup&gt;13&lt;/sup&gt;&lt;/span&gt; Notably, BCMA expression in pDCs was first reported as early as 2017.&lt;span&gt;&lt;sup&gt;14&lt;/sup&gt;&lt;/span&gt; Here, we investigated whether anti-BCMA immunotherapy, including bsAbs and CAR-T cells, contributes to increased viral susceptibility by affecting the pDC compartment in MM patients.&lt;/p&gt;&lt;p&gt;Overall, 388 unique samples from 72 MM patients were assessed in this study in multiple cohorts (Table S1). Patient characteristics are summarized in Tables S2–S5. BCMA gene expression was analyzed using publicly available single-cell RNA sequencing (scRNA-seq) datasets from healthy donor (HD) b","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784221","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":"An Italian cartography of VEXAS-related thrombosis","authors":"Giorgia Ranucci,&nbsp;Maria Rosaria Pascale,&nbsp;Vittorio Forte,&nbsp;Elisa Diral,&nbsp;Corrado Campochiaro,&nbsp;Jacqueline Ferrari,&nbsp;Mariachiara Cuccaro,&nbsp;Chiara Cattaneo,&nbsp;Francesca Crisafulli,&nbsp;Lucia Cardillo,&nbsp;Valeria Renola,&nbsp;Elisa Meddi,&nbsp;Marianna Velocci,&nbsp;Elisa Casciani,&nbsp;Francesca Romano,&nbsp;Pellegrino Musto,&nbsp;Serafina Barbato,&nbsp;Giorgia Battipaglia,&nbsp;Marco Frigeni,&nbsp;Erika Morsia,&nbsp;Arianna Savi,&nbsp;Cristina Papayannidis,&nbsp;Elena Crisà,&nbsp;Laura Cicconi,&nbsp;Isabella Capodanno,&nbsp;Alfonso Fiumarella,&nbsp;Antonio Pierini,&nbsp;Massimo Breccia,&nbsp;Giovanni Orsolini,&nbsp;Giulia Rivoli,&nbsp;Sara Bindoli,&nbsp;Davide Firinu,&nbsp;Antonio Vitale,&nbsp;Bruno Fattizzo,&nbsp;Monica Bocchia,&nbsp;Luca Cantarini,&nbsp;Chiara Pinton,&nbsp;Gabriele Todisco,&nbsp;Nicola Toschi,&nbsp;Paola Triggianese,&nbsp;Adriano Venditti,&nbsp;Maria Teresa Voso,&nbsp;Carmelo Gurnari","doi":"10.1002/hem3.70451","DOIUrl":"https://doi.org/10.1002/hem3.70451","url":null,"abstract":"<p>Thrombotic events (TEs) occur in up to 40% of patients with vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic (VEXAS) syndrome, but data on its clinical-genomics features and anticoagulation strategies are limited. To gain more insight into this, we conducted a two-step study evaluating the prevalence and outcome of TE in VEXAS. First, among 1086 patients followed for TEs, 198 were men aged &gt;40 years with unprovoked thrombosis and no known thrombophilia; 21 also had at least one VEXAS-compatible feature and underwent <i>UBA1</i> exon 3 testing. No <i>UBA1</i> mutation was detected in these 21 patients. Next, we leveraged our Italian VEXAS network, and we accrued 87 molecularly confirmed Italian VEXAS cases (median age 70 years). Any history of TE was documented in 43/87 patients (49%), deep vein thrombosis being the most common (71%). Because follow-up varied, incident thrombosis was analyzed using a time-to-first-event framework from molecular VEXAS diagnosis, with death without prior TE treated as a competing event. Among 49 patients without prior/concomitant TE, five developed incident post-diagnosis TE; the 24-month cumulative incidence was 18.3%. Thrombophilia testing revealed a 15% co-occurrence, including heterozygous Factor V Leiden, Factor II G20210A, and anti-cardiolipin antibodies. Treatments comprised direct oral anticoagulants (DOACs) (51%), low molecular weight heparin (LMWH) (28%), Fondaparinux (14%), and vitamin K antagonists (AVKs) (7%). Notably, 27% experienced multiple TEs, of which 22% occurring despite anticoagulation during disease flares. Our findings provide an updated cartography of VEXAS-related TE, suggesting early screening for thrombophilia in these patients to inform both personalized anticoagulation and disease-control strategies.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784104","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":"An Italian cartography of VEXAS-related thrombosis","authors":"Giorgia Ranucci,&nbsp;Maria Rosaria Pascale,&nbsp;Vittorio Forte,&nbsp;Elisa Diral,&nbsp;Corrado Campochiaro,&nbsp;Jacqueline Ferrari,&nbsp;Mariachiara Cuccaro,&nbsp;Chiara Cattaneo,&nbsp;Francesca Crisafulli,&nbsp;Lucia Cardillo,&nbsp;Valeria Renola,&nbsp;Elisa Meddi,&nbsp;Marianna Velocci,&nbsp;Elisa Casciani,&nbsp;Francesca Romano,&nbsp;Pellegrino Musto,&nbsp;Serafina Barbato,&nbsp;Giorgia Battipaglia,&nbsp;Marco Frigeni,&nbsp;Erika Morsia,&nbsp;Arianna Savi,&nbsp;Cristina Papayannidis,&nbsp;Elena Crisà,&nbsp;Laura Cicconi,&nbsp;Isabella Capodanno,&nbsp;Alfonso Fiumarella,&nbsp;Antonio Pierini,&nbsp;Massimo Breccia,&nbsp;Giovanni Orsolini,&nbsp;Giulia Rivoli,&nbsp;Sara Bindoli,&nbsp;Davide Firinu,&nbsp;Antonio Vitale,&nbsp;Bruno Fattizzo,&nbsp;Monica Bocchia,&nbsp;Luca Cantarini,&nbsp;Chiara Pinton,&nbsp;Gabriele Todisco,&nbsp;Nicola Toschi,&nbsp;Paola Triggianese,&nbsp;Adriano Venditti,&nbsp;Maria Teresa Voso,&nbsp;Carmelo Gurnari","doi":"10.1002/hem3.70451","DOIUrl":"https://doi.org/10.1002/hem3.70451","url":null,"abstract":"<p>Thrombotic events (TEs) occur in up to 40% of patients with vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic (VEXAS) syndrome, but data on its clinical-genomics features and anticoagulation strategies are limited. To gain more insight into this, we conducted a two-step study evaluating the prevalence and outcome of TE in VEXAS. First, among 1086 patients followed for TEs, 198 were men aged &gt;40 years with unprovoked thrombosis and no known thrombophilia; 21 also had at least one VEXAS-compatible feature and underwent <i>UBA1</i> exon 3 testing. No <i>UBA1</i> mutation was detected in these 21 patients. Next, we leveraged our Italian VEXAS network, and we accrued 87 molecularly confirmed Italian VEXAS cases (median age 70 years). Any history of TE was documented in 43/87 patients (49%), deep vein thrombosis being the most common (71%). Because follow-up varied, incident thrombosis was analyzed using a time-to-first-event framework from molecular VEXAS diagnosis, with death without prior TE treated as a competing event. Among 49 patients without prior/concomitant TE, five developed incident post-diagnosis TE; the 24-month cumulative incidence was 18.3%. Thrombophilia testing revealed a 15% co-occurrence, including heterozygous Factor V Leiden, Factor II G20210A, and anti-cardiolipin antibodies. Treatments comprised direct oral anticoagulants (DOACs) (51%), low molecular weight heparin (LMWH) (28%), Fondaparinux (14%), and vitamin K antagonists (AVKs) (7%). Notably, 27% experienced multiple TEs, of which 22% occurring despite anticoagulation during disease flares. Our findings provide an updated cartography of VEXAS-related TE, suggesting early screening for thrombophilia in these patients to inform both personalized anticoagulation and disease-control strategies.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784108","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":"The bidirectional relationship between JAK2V617F allele burden and inflammation in polycythaemia vera: Insights from interferon and ruxolitinib therapy","authors":"Tiziano Barbui,&nbsp;Paola Guglielmelli,&nbsp;Alessandro Maria Vannucchi","doi":"10.1002/hem3.70464","DOIUrl":"https://doi.org/10.1002/hem3.70464","url":null,"abstract":"&lt;p&gt;Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal hematopoietic stem cell disorders driven by recurrent mutations in &lt;i&gt;JAK2&lt;/i&gt;, &lt;i&gt;CALR&lt;/i&gt;, or &lt;i&gt;MPL&lt;/i&gt;, resulting in constitutive activation of the JAK–STAT signaling pathway.&lt;/p&gt;&lt;p&gt;Although these mutations are central to disease initiation, accumulating evidence indicates that chronic inflammation plays a pivotal role in disease progression and clinical manifestations, making it a relevant therapeutic target.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;In PV, the interplay between inflammation and clonal hematopoiesis appears particularly important as inflammatory signals may promote the expansion and persistence of the &lt;i&gt;JAK2V617F&lt;/i&gt; mutant clone, thereby influencing its accumulation over time. Within this context, the two principal targeted agents, pegylated interferon-α and ruxolitinib, both exert anti-inflammatory effects. Interferon therapy in PV evolved from conventional and pegylated IFN-α2a to ropeginterferon alfa-2b (Ropeg), a long-acting formulation that enables sustained treatment while preserving disease-modifying activity.&lt;/p&gt;&lt;p&gt;Recent data indicate that ropeginterferon and ruxolitinib differ in clonal suppression, likely due to distinct interactions with the inflammatory microenvironment, providing the rationale for this brief review of their biological and therapeutic implications.&lt;/p&gt;&lt;p&gt;Among inflammatory mediators, IL-1 signaling appears particularly relevant. Elevated IL-1 levels have been demonstrated in both MPN patients and &lt;i&gt;JAK2V617F&lt;/i&gt; mouse models. Genetic deletion of IL-1R1 normalizes blood counts, reduces splenomegaly and fibrosis, and decreases mutant hematopoietic stem/progenitor cells, whereas exogenous IL-1β promotes myeloid expansion and fibrosis.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Complementary studies showed that IL-1β is produced by &lt;i&gt;JAK2V617F&lt;/i&gt; hematopoietic cells and contributes to bone marrow niche damage, myelofibrosis, and osteosclerosis, with additive therapeutic effects observed when IL-1β suppression is combined with ruxolitinib.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Importantly, IL-1β also appears involved in disease initiation, since its inhibition reduces engraftment and clonal expansion of JAK2-mutant HSCs and delays progression from &lt;i&gt;JAK2V617F&lt;/i&gt; CHIP to overt MPN.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Upstream of IL-1β, the NLRP3 inflammasome has emerged as a critical regulator of inflammatory activation. Deletion of Nlrp3 abolishes IL-1β and IL-18 release and attenuates thrombocytosis, granulocytosis, HSPC expansion, splenomegaly, and fibrosis in &lt;i&gt;JAK2V617F&lt;/i&gt; models. Pharmacologic NLRP3 inhibition reverses established disease manifestations, supporting its therapeutic potential.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;TNF-α also promotes clonal dominance&lt;i&gt;. JAK2V617F&lt;/i&gt; induces TNF-α production, while mutant progenitors display resistance to TNF-α-mediated suppression, unlike nor","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784107","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":"No association between temozolomide maintenance and survival after first-line treatment in primary CNS lymphoma","authors":"Nashif Chowdhury,&nbsp;Jenni Niemi,&nbsp;Haris Babačić,&nbsp;Hanna-Maija Rantakylö,&nbsp;Ingrid Glimelius,&nbsp;Mats Jerkeman,&nbsp;Mats Hellström","doi":"10.1002/hem3.70445","DOIUrl":"https://doi.org/10.1002/hem3.70445","url":null,"abstract":"&lt;p&gt;Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of diffuse large B-cell lymphoma (DLBCL) characterized by infiltration of malignant B cells into the central nervous system (CNS).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Fit patients are treated with high-dose methotrexate (HD-MTX)–based polychemotherapy followed by thiotepa-containing high-dose chemotherapy and autologous stem cell transplantation (ASCT).&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; For patients unsuitable for ASCT, induction treatment is consolidated with high-dose cytarabine and low-dose whole-brain radiotherapy (WBRT).&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Patients unsuitable for HD-MTX can receive first-line treatment with a single alkylator, such as temozolomide (TMZ) and WBRT. Despite therapeutic advances and high response rates, over half of the patients with PCNSL relapse within 2 years after diagnosis.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; TMZ maintenance treatment has been suggested to reduce relapse rates and improve overall survival (OS) for patients with post-induction complete remission (CR) or partial remission (PR). Therefore, its administration is supported by international guidelines, including the European Hematology Association and European Society for Medical Oncology (EHA-ESMO) joint recommendations&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; and the National Comprehensive Cancer Network (NCCN) Guidelines for B-Cell Lymphomas (Version 3.2026). However, implementation of TMZ maintenance varies across clinical settings, allowing real-world evaluation of the association between TMZ maintenance and OS.&lt;/p&gt;&lt;p&gt;To address the clinical evidence gap regarding TMZ maintenance benefits, we aimed to evaluate its OS gain in a retrospective cohort of 110 patients with PCNSL diagnosed between 2009 and 2022 at two Swedish university hospitals: Uppsala University Hospital (&lt;i&gt;n&lt;/i&gt; = 60) and Skåne University Hospital in Lund (&lt;i&gt;n&lt;/i&gt; = 50), respectively. The Uppsala subgroup was included from the U-CAN population-based prospective biobank.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; We collected information on patient characteristics, treatments, and outcomes. We performed univariable survival analyses with Kaplan–Meier curves and time-dependent Cox proportional hazards models, tested with two-sided log-rank and Wald tests, respectively, at a statistical significance threshold of &lt;i&gt;α&lt;/i&gt; = 0.05. OS was the primary outcome, defined as the time from diagnosis to death or last vital status assessment. To adjust for the effects of different treatments and account for potential immortal time bias, we performed multivariable analyses with time-dependent Cox proportional hazards models by introducing the treatment effects on OS at the time of treatment start, whereas CR was introduced at the end of induction. Study design and methodology are available in Supporting Information S2: Supplementary Methods.&lt;/p&gt;&lt;p&gt;In the entire cohort, 84 patients (76%) received HD-MTX, mainly the MPV (HD-MTX, procarbazine, and vincristine) regimen, given to 62","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784187","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":"No association between temozolomide maintenance and survival after first-line treatment in primary CNS lymphoma","authors":"Nashif Chowdhury,&nbsp;Jenni Niemi,&nbsp;Haris Babačić,&nbsp;Hanna-Maija Rantakylö,&nbsp;Ingrid Glimelius,&nbsp;Mats Jerkeman,&nbsp;Mats Hellström","doi":"10.1002/hem3.70445","DOIUrl":"https://doi.org/10.1002/hem3.70445","url":null,"abstract":"&lt;p&gt;Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of diffuse large B-cell lymphoma (DLBCL) characterized by infiltration of malignant B cells into the central nervous system (CNS).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Fit patients are treated with high-dose methotrexate (HD-MTX)–based polychemotherapy followed by thiotepa-containing high-dose chemotherapy and autologous stem cell transplantation (ASCT).&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; For patients unsuitable for ASCT, induction treatment is consolidated with high-dose cytarabine and low-dose whole-brain radiotherapy (WBRT).&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Patients unsuitable for HD-MTX can receive first-line treatment with a single alkylator, such as temozolomide (TMZ) and WBRT. Despite therapeutic advances and high response rates, over half of the patients with PCNSL relapse within 2 years after diagnosis.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; TMZ maintenance treatment has been suggested to reduce relapse rates and improve overall survival (OS) for patients with post-induction complete remission (CR) or partial remission (PR). Therefore, its administration is supported by international guidelines, including the European Hematology Association and European Society for Medical Oncology (EHA-ESMO) joint recommendations&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; and the National Comprehensive Cancer Network (NCCN) Guidelines for B-Cell Lymphomas (Version 3.2026). However, implementation of TMZ maintenance varies across clinical settings, allowing real-world evaluation of the association between TMZ maintenance and OS.&lt;/p&gt;&lt;p&gt;To address the clinical evidence gap regarding TMZ maintenance benefits, we aimed to evaluate its OS gain in a retrospective cohort of 110 patients with PCNSL diagnosed between 2009 and 2022 at two Swedish university hospitals: Uppsala University Hospital (&lt;i&gt;n&lt;/i&gt; = 60) and Skåne University Hospital in Lund (&lt;i&gt;n&lt;/i&gt; = 50), respectively. The Uppsala subgroup was included from the U-CAN population-based prospective biobank.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; We collected information on patient characteristics, treatments, and outcomes. We performed univariable survival analyses with Kaplan–Meier curves and time-dependent Cox proportional hazards models, tested with two-sided log-rank and Wald tests, respectively, at a statistical significance threshold of &lt;i&gt;α&lt;/i&gt; = 0.05. OS was the primary outcome, defined as the time from diagnosis to death or last vital status assessment. To adjust for the effects of different treatments and account for potential immortal time bias, we performed multivariable analyses with time-dependent Cox proportional hazards models by introducing the treatment effects on OS at the time of treatment start, whereas CR was introduced at the end of induction. Study design and methodology are available in Supporting Information S2: Supplementary Methods.&lt;/p&gt;&lt;p&gt;In the entire cohort, 84 patients (76%) received HD-MTX, mainly the MPV (HD-MTX, procarbazine, and vincristine) regimen, given to 62","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784105","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}