Blood advances最新文献

{"title":"Transcriptomic atlas reveals organ-specific disease tolerance in sickle cell mice.","authors":"Anne Grunenwald, Julie Peliconi, Julien Lavergne, Margot Revel, Elodie Voilin, Tania Robe-Rybkine, Gilles Crambert, Jordan D Dimitrov, Olivier Blanc-Brude, Lubka T Roumenina","doi":"10.1182/bloodadvances.2024013435","DOIUrl":"10.1182/bloodadvances.2024013435","url":null,"abstract":"<p><strong>Abstract: </strong>Sickle cell disease (SCD) is the most common genetic disease in the world and a societal challenge. SCD is characterized by multiorgan injury related to intravascular hemolysis. To understand tissue-specific responses to intravascular hemolysis and exposure to heme, we present a transcriptomic atlas of the primary target organs of hemoglobin S (HbSS) vs hemoglobin 1 (HbAA) transgenic SCD mice. We explored the transcriptomes of the liver, kidney, heart, lung, and bone marrow from HbAA and HbSS Townes littermates at resting state and their changes after the injection of heme, assessed by RNA sequencing. Inflammation and myeloid cell signatures were omnipresent in resting HbSS organs, with the liver being the most affected. The injection of heme triggered a robust inflammatory response in HbAA mice. Signatures of exposure to heme in HbAA mice were downstream of toll like receptor 4, sensor of lipopolysaccharides but also of heme, interleukin-1β (IL-1β), IL-6, and interferon gamma, similarly to HbSS mice at rest. Nevertheless, HbSS mice were strikingly unresponsive to the heme administration, irrespective of the organ. This tolerance was driven by upregulation of the heme-detoxifying enzyme heme oxygenase-1 and was abrogated by its specific inhibition. Therefore, HbSS mice develop robust protective mechanisms, which may explain how they and patients with SCD survive bouts of severe hemolysis.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1405-1419"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nivolumab and rituximab in treatment-naïve follicular lymphoma: the phase 2 1st FLOR study.","authors":"Allison Barraclough, Sze Ting Lee, Melinda Burgess, Leonid Churilov, Geoff Chong, Denise Lee, Michael Gilbertson, Tineke Fancourt, Kate Manos, David S Ritchie, Rachel M Koldej, Andrew M Scott, Colm Keane, Eliza A Hawkes","doi":"10.1182/bloodadvances.2024015487","DOIUrl":"10.1182/bloodadvances.2024015487","url":null,"abstract":"<p><strong>Abstract: </strong>Follicular lymphoma (FL) outcomes are influenced by host immune activity. CD20-directed therapy plus programmed cell death 1 inhibition (PD-1i) increases T-cell tumor killing and natural killer cell antibody-dependent cell cytotoxicity. Mounting evidence supports immune priming using PD-1i before cancer directed agents. Our multicenter, phase 2 1st FLOR study enrolled 39 patients with previously untreated advanced-stage FL to receive 4 cycles of nivolumab (240 mg), then 4 cycles of 2-weekly nivolumab plus rituximab 375 mg/m2 (induction), then 1 year of monthly nivolumab (480 mg) plus 2 years of 2-monthly rituximab maintenance. Participants with complete response (CR) after nivolumab priming continued nivolumab monotherapy. The primary end point was toxicity during induction. Adverse events of grade ≥3 during induction occurred in 33% (n = 13); most commonly elevated amylase/lipase (15%), liver enzyme derangement (11%), and infection (10%). Three patients discontinued nivolumab secondary to toxicity. Overall response rate was 92% (CR, 59%). Median follow-up was 51 months. Median and 4-year progression-free survival (PFS) were 61 months (95% confidence interval [CI], 2-72) and 58% (95% CI, 34-97); 70% of responders remained in CR. The 4-year overall survival was 95%. High baseline total metabolic tumor volume (TMTV) and total lesion glycolysis conferred inferior PFS (P = .04 and P = .02). Additionally, high baseline tumor CD8A gene expression was associated with improved PFS (P = .03). Nivolumab priming followed by nivolumab-rituximab in treatment-naïve FL is associated with favorable toxicity and high response rates, potentially providing an alternative to chemotherapy. TMTV and high tumor CD8A expression are promising immunotherapy biomarkers for FL. This trial was registered at www.ClinicalTrials.gov as #NCT03245021.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1432-1441"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imbalanced VWF-ADAMTS13 axis contributes to the detrimental impact of a preceding respiratory tract infection on stroke.","authors":"Rakesh B Patel, Abhishek B Jha, Aditi Jain, Abhishek K Verma, Saurabh Saini, Joshua Muia, Prajwal Gurung, Stanley Perlman, Ivan Budnik, Anil K Chauhan","doi":"10.1182/bloodadvances.2024014622","DOIUrl":"10.1182/bloodadvances.2024014622","url":null,"abstract":"<p><strong>Abstract: </strong>Respiratory tract infections (RTIs) caused by bacteria or viruses are associated with stroke severity. Recent studies have revealed an imbalance in the von Willebrand factor (VWF)-ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) axis in patients with RTIs, including coronavirus disease 2019. We examined whether this imbalance contributes to RTI-mediated stroke severity. Wild-type (WT), Vwf-/-, or Adamts13-/- mice with respective littermate controls (Vwf+/+ or Adamts13+/+) were infected intranasally with sublethal doses of Staphylococcus aureus (on days 0, 2, and 5) or mouse-adapted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; on day 0) and subjected to transient (30 or 45 minutes) cerebral ischemia followed by reperfusion. In S aureus-infected mice, infarct volumes were assessed on day 2 and functional outcomes on weeks 1 and 4 after reperfusion. In SARS-CoV-2-infected mice, infarct volumes and functional outcomes (Bederson score) were assessed on day 1 after reperfusion. We demonstrated that S aureus or SARS-CoV-2 RTI was accompanied by an imbalance in the VWF-ADAMTS13 axis and an increase in plasma levels of interleukin-6, C-X-C motif chemokine ligand 1, and monocyte chemoattractant protein-1, which was associated with larger infarcts and worse functional outcomes (P < .05 vs mock infection). S aureus- or SARS-CoV-2-infected Vwf-/- mice exhibited reduced infarcts and improved functional outcomes, whereas infected Adamts13-/- mice displayed greater stroke severity (P < .05 vs control). In the models of RTI preceding stroke, VWF contributes to stroke severity, whereas ADAMTS13 is protective.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1330-1341"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal relatedness as a prognostic marker in Richter transformation of chronic lymphocytic leukemia: a systematic review.","authors":"Aisling Barrett, Callum Harris, Toby A Eyre","doi":"10.1182/bloodadvances.2024015594","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015594","url":null,"abstract":"<p><p>Disease shift of chronic lymphocytic leukemia (CLL) to diffuse large B-cell lymphoma (DLBCL), so-called Richter transformation (RT), is a catastrophic clinical event. Rarely survival can outperform expectations and accurate prognostication for patients may affect therapeutic choices. To date, prognosis has relied on readily available factors such as TP53 disruption, prior CLL treatment status and performance score. Recently, shared clonality assessment by immunoglobulin heavy-chain variable (IgHV) region sequencing of the CLL and RT has been considered therapeutically relevant, but this is infrequently performed. We performed a systematic review of peer-reviewed manuscripts where outcomes in relation to clonal relatedness and lack thereof (clonally-related and -unrelated RT-DLBCL) were examined. Fifteen manuscripts which included 336 patients were found, of which six compared survival outcomes between the two groups in a statistically meaningful way. Two analyses showed no difference in survival outcomes with four studies reporting a significantly poorer prognosis with clonally-related RT-DLBCL. In two of these studies the baseline characteristics of clonally-related and -unrelated groups were compared and the clonally-related cases were enriched for underlying CLL which was TP53 disrupted, IgHV unmutated, more heavily pretreated and exhibiting stereotyped B-cell receptor VH CDR3, as well as RT-DLBCL which was MYD88wt. We demonstrate that although clonal relatedness of the underlying CLL confers a poorer survival, this is not demonstrated in any study to be independent of other well-described clinical and genomic variables known to influence outcome in RT-DLBCL. Further independent validation of this prognostic factor is required to help guide universal adoption into clinical practice.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699702","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":"Real World Outcomes for Young Adult Patients Receiving CD19 CAR T-cell Therapy.","authors":"Hannah Lust, Liora M Schultz, Soyang Kwon, Gregory W Roloff, Ibrahim Aldoss, Christina Baggott, Samuel John, Jenna Rossoff, Kevin O McNerney, Vanessa A Fabrizio, Julie-An Talano, Amy Moskop, Kevin J Curran, Christine L Phillips, Nicole A Karras, Susanne H C Baumeister, Stacy Cooper, Michelle L Hermiston, Prakash Satwani, Muna Qayed, Sunil Sudhir Raikar, Margaret L MacMillan, Erin M Hall, Khanh Nguyen, Ryan D Cassaday, Noam E Kopmar, Vamsi K Kota, John Mathews, Paul J Shaughnessy, Marc S Schwartz, Abdullah Ladha, George Yaghmour, Muthu Kumaran, Veronika Bachanova, Sean I Tracy, Tamer Othman, Marlise R Luskin, Evan C Chen, Anjali S Advani, Nikeshan Jeyakumar, Katharine Miller, Amy Zhang, Bijal D Shah, Lori S Muffly, Rawan G Faramand","doi":"10.1182/bloodadvances.2024014846","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014846","url":null,"abstract":"<p><p>Tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel) are approved CD19 CAR T products for young adults (YAs) with relapsed/refractory B-ALL. A distinct analysis of YAs receiving commercial CD19 CAR T has not been reported. Utilizing retrospective data from the Pediatric Real-World CAR T Consortium and the Real-World Outcomes of CAR T in Adult ALL collaboration, we describe efficacy and safety of tisa-cel and brexu-cel in 70 young adults (18-26 years; tisa-cel: 50, brexu-cel: 20). Cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity syndrome (ICANS) were observed more frequently for brexu-cel vs tisa-cel (CRS= 85% vs 56%, p=0.01; ICANS= 40% vs 18%, p=0.05). CR rates were similar between products at 80% for brexu-cel and 88% for tisa-cel (p=0.39). Relapse free survival (RFS) at 12 months was 46% for brexu-cel (95% CI 31-81%) and 36% for tisa-cel (95% CI 26-52%, p=0.79). Durability of remission over 12 months was 61% for brexu-cel (95% CI 41-93%) vs 41% for tisa-cel (95% CI 27-61%, p=0.12). 12-month overall survival (OS) for brexu-cel was 84% (95% CI 81-100) vs 68% for tisa-cel (95% CI 56-85, HR 1.9, p=0.35). In multivariate analysis, low disease burden was associated with improved OS (HR 0.23, 95% CI 0.06-0.86, p=0.03), while inotuzumab pre-CAR T was associated with inferior outcomes (OS HR 6.32, 95% CI 1.48-27, p=0.01; RFS HR 3.65, 95% CI 1.41-9.46, p=0.008). This study demonstrates comparable real-world efficacy among young adults receiving CD19 CAR T therapy irrespective of CAR T construct, however, rates of toxicity appear higher with brexu-cel.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699708","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 a protease-resistant ADAMTS13 to improve stability against proteolytic degradation.","authors":"Veronica DeYoung, Rex Huang, Hasam Madarati, Rida Malik, Peter Anthony Andrisani, Cherie Teney, Colin A Kretz","doi":"10.1182/bloodadvances.2024015212","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015212","url":null,"abstract":"<p><p>Recombinant ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was recently approved by the FDA for the treatment of heritable thrombotic thrombocytopenic purpura (TTP), and preclinical studies have demonstrated its efficacy in treating other thrombotic conditions. However, the current ADAMTS13 product is susceptible to degradation by proteases, which may reduce its therapeutic efficacy. Protease-sensitive sites were mapped to the linker regions in ADAMTS13. The linkers were mutated to generate T4L/T8L-ADAMTS13, and an additional elastase cleavage site was also disrupted (T4L/T8L-ADAMTS13[I380G]). Degradation of each ADAMTS13 mutant was tested using purified coagulation or neutrophil proteases, activated neutrophils, or with plasma-based assays. FRETS-VWF73 and microfluidic flow assays were used to characterize their activity. Thrombin, factor Xa, factor XIa, kallikrein, and plasmin cleaved WT-ADAMTS13 at two sites. Mutation of both the T4- and T8-linkers protects against degradation at these sites over 3 hours. T4L/T8L-ADAMTS13(I380G) was resistant to elastase degradation. T4L/T8L-ADAMTS13 is stable in plasma thrombin generation assays and fibrinolysis assays, and T4L/T8L-ADAMTS13(I380G) exhibits improved stability to activated neutrophils. T4L/T8L-ADAMTS13 exhibited similar activity to WT-ADAMTS13 using FRETS-VWF73 and in a microfluidic von Willebrand Factor (VWF)-platelet string cleavage assay. This work identifies prominent protease cleavage sites within ADAMTS13 and demonstrates that disruption of these sites does not impair its capacity to regulate VWF. Future work will explore the therapeutic efficacy of protease-resistant ADAMTS13 in vivo.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699705","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":"Validation of Risk Assessment Models for Venous Thromboembolism in Cancer Patients Receiving Systemic Therapies.","authors":"Nikola Vladić, Cornelia Englisch, Julia Maria Berger, Florian Moik, Anna Sophie Berghoff, Matthias Preusser, Ingrid Pabinger, Cihan Ay","doi":"10.1182/bloodadvances.2025016044","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016044","url":null,"abstract":"<p><p>Cancer increases the risk of venous thromboembolism (VTE). To identify patients with cancer at high VTE risk that might benefit from primary thromboprophylaxis, several risk assessment models (RAMs) have been developed. The evolution of anti-cancer therapies, including implementation of targeted- and immunotherapeutic agents, might affect VTE risk and risk prediction. Therefore, we aimed to evaluate the performance of six externally validated RAMs (Khorana score, PROTECHT, CONKO, COMPASS-CAT, CATScore and EHR-CAT) in a prospective observational cohort study of patients with cancer initiating contemporary systemic anti-cancer therapies. Eight-hundred-six patients (49.5% women) with a median age of 61 years (interquartile range [IQR]: 53-69) were included. The most common cancer types were lung (21.8%), breast (10.8%), and pancreatic (10.3%). Anti-cancer therapies initiated at study inclusion included chemotherapy (48.3%), combination of chemotherapy and ICI (16.6%), ICI monotherapy (15.4%), and targeted agents (19.7%). During an observation period of six months, 91 patients were diagnosed with VTE (cumulative incidence 11.2%, 95% confidence interval [CI]: 9.0-13.3). The discriminatory performance of the RAMs varied, with the best c-statistic seen with the CATScore, while the COMPASS-CAT score showed the lowest area under the curve (AUC) value (c-statistics [95% CI]: Khorana score: 0.53 [0.50-0.56], PROTECHT: 0.58 [0.56-0.61], CONKO: 0.54 [0.51-0.57], COMPASS-CAT: 0.50 [0.47-0.53], CATScore: 0.65 [0.62-0.67]) and EHR-CAT: 0.55 [0.52-0.57]. Overall, we observed a poor to modest discriminatory performance of the RAMs in our contemporary cohort of patients with cancer, with the CATScore performing best among all evaluated scores.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673340","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":"Nitrated Fatty Acids protect against Acute Kidney Injury in Sickle Cell Disease.","authors":"Mara Carreño, Diane Lenhart, Rajat Pant, Paritosh Mondal, Sonia R Salvatore, Maria F Pires, Enrico M Novelli, Francisco Jose Schopfer, Samit Ghosh, Dario A Vitturi","doi":"10.1182/bloodadvances.2024015038","DOIUrl":"10.1182/bloodadvances.2024015038","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673320","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":"Venous Thrombosis Unchained: Pandora's Box of Non-Inflammatory Mechanisms.","authors":"Sophie Robyn Megan Smith, Neil V Morgan, Alexander Brill","doi":"10.1182/bloodadvances.2024014114","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014114","url":null,"abstract":"<p><p>Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), represents a complex pathological process extending far beyond inflammatory mechanisms. This review comprehensively examines the multifaceted non-inflammatory mechanisms underlying thrombosis development, integrating insights from molecular, physiological, and systemic levels. Blood flow dynamics and endothelial function are known to be critical regulators of thrombus development. Platelets and microparticles play important roles beyond conventional inflammatory responses, actively contributing to thrombus formation through intricate molecular interactions. Metabolic syndrome and insulin resistance are associated with thrombotic risk, demonstrating the complex interplay between metabolic disorders and DVT. Certain genetic mutations also predispose individuals to venous thrombosis. Emerging research has discovered the essential role of previously underappreciated factors such as products of gut microbiota or endothelial glycocalyx modifications. Molecular regulators such as microRNAs and hormonal disbalance further illustrate the complex mechanisms of venous thrombosis. Interestingly, circadian rhythms exhibit certain influence on thrombotic potential, introducing chronobiology as emerging variable affecting the risk of thrombosis. Based on these insights, future therapeutic strategies may include various interventions targeting or at least considering metabolic, molecular, and systemic non-inflammatory factors. Potential approaches include personalized risk stratification, microbiome modulation, endothelial protection approaches, and chronotherapy-based therapeutic modalities, that would ensure promising more efficient and safe thrombosis management.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673345","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":"Thrombosis, major bleeding, and mortality in 1 079 myelofibrosis patients, a matched population-based study.","authors":"Anneli Enblom Larsson, Henrik Renlund, Björn I Andreasson, Henrik Holmberg, Maria Liljeholm, Anders Själander","doi":"10.1182/bloodadvances.2025016247","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016247","url":null,"abstract":"<p><p>Bleeding and thrombotic events are known complications in myeloproliferative neoplasms (MPN), but few studies are exclusively focusing on patients with myelofibrosis (MF). In this nationwide population-based study, we assessed the frequency of major bleeding, thrombotic events and all cause-mortality in 1 079 patients diagnosed with MF and 5 395 matched controls, using multiple Swedish Health Care Registers. Major bleeding, arterial and venous events were seen at a rate of 2.55, 2.59 and 1.06 events per 100 years in patients with MF. Compared to controls, the rates of bleedings, arterial events, venous events and mortality were increased, HR 3.78 (95% CI 2.98-4.79, p<0.001), HR 1.73 (1.40-2.12, p<0.001), 2.75 (1.93-3.90, p<0.001) and HR 3.92 (3.50-4.40, p<0.001) respectively. Patients treated with JAK inhibitors (JAKi) had higher rates of major bleeding (5.33), arterial events (4.67) and venous events (1.56) than patients with no ongoing symptoms-directed therapy (rates 2.32, 2.15 and 0.79) or hydroxyurea (rates 2.05, 2.35 and 1.27). Use of JAKi, low-molecular-weight heparin (LMWH), previous arterial or venous event and higher age were identified as independent risk factors for a new arterial or venous event. A previous venous event, a higher leukocyte count at diagnosis and ongoing JAKi treatment were associated with an increased risk of major bleeding. Current study shows that patients with MF have higher rates of thromboembolic events and major bleeding than described in other MPN and thromboembolic complications and major bleeding diverges in the different treatment groups.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673336","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}