Blood advances最新文献

{"title":"Lymphoma B cells remodel bone marrow stromal cells into extracellular matrix-producing cancer-associated fibroblasts.","authors":"Elise Dessauge, Baptiste Brauge, Simon Léonard, Alicia Beyou, Camille Laurent, Valentin Isen, Nicolas Barbier, Céline Monvoisin, Thomas Lejeune, Jérôme Destin, Florence Jouan, Judikael Saout, Francisco Llamas-Gutierrez, Franck Morschhauser, Sandrine Roulland, David Roulois, Frédéric Mourcin, Karin Tarte","doi":"10.1182/bloodadvances.2024015616","DOIUrl":"10.1182/bloodadvances.2024015616","url":null,"abstract":"<p><strong>Abstract: </strong>Bone marrow (BM) involvement is a common feature of germinal center-derived B-cell lymphomas and is associated with a poor prognosis. In particular, follicular lymphoma (FL) infiltrates the BM in 70% of cases, and analysis of in vitro-expanded FL BM mesenchymal stromal cells (MSCs) has revealed an extensive alteration of BM stromal cell phenotypic, transcriptomic, and functional profiles. However, the mechanisms underlying the direct interplay between lymphoma B cells and their permissive stromal niche in situ have not yet been identified. In this study, we identified a significant remodeling of extracellular matrix (ECM) composition and organization in the BM of patients with FL and in a murine model of lymphoma B-cell BM xenograft. In particular, murine leptin receptor (LepR+) MSCs were identified by single-cell RNA sequencing as engaged in a bidirectional cross talk with malignant B cells, triggering their specific and progressive reprogramming and commitment toward a phenotype resembling that of human ECM/transforming growth factor β (TGFβ) myofibroblastic cancer-associated fibroblasts (CAFs) and FL-CAFs. Kinetic analysis of FL BM samples showed that ECM and TGFβ deregulation persisted after treatment, suggesting it may contribute to disease persistence and relapse. Overall, this work sheds new light on the kinetics and mechanisms of BM stromal niche reshaping in B-cell lymphomas.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3455-3468"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959690","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":"Delayed T-cell recovery after hematopoietic cell transplantation is associated with decreased overall survival in adults.","authors":"Miguel-Angel Perales, Marcie Riches, Naya He, Michael J Martens, Roy F Chemaly, Christopher E Dandoy, Joshua A Hill, Miguel Angel Diaz, Shahrukh Hashmi, Susan Prockop, Hillard M Lazarus, Amer M Beitinjaneh, Gerhard C Hildebrandt, Jeffery J Auletta, Paul Szabolcs","doi":"10.1182/bloodadvances.2024015288","DOIUrl":"10.1182/bloodadvances.2024015288","url":null,"abstract":"<p><strong>Abstract: </strong>Allogeneic hematopoietic cell transplantation (allo-HCT) can provide curative treatment for hematologic malignancies but is associated with prolonged lymphopenia that may contribute to an increased risk of infection and relapse, resulting in decreased survival. We hypothesized that patients with rapid and robust CD4 T- and B-cell recovery have improved survival and decreased treatment-related mortality (TRM). A total of 2089 patients were included who underwent first allo-HCT for acute myeloid leukemia/acute lymphoblastic leukemia/myelodysplastic syndrome from 2008 to 2019 reported to the Center for International Blood and Marrow Transplant Research with available CD4 counts at days 100 and 180. Patients (median age, 51 years [range, 2-75]) were categorized into 4 groups based on graft-versus-host disease (GVHD) prophylaxis: ex vivo T-cell depletion (TCD/CD34), posttransplant cyclophosphamide, calcineurin inhibitor alone (CNI), or CNI with antithymocyte globulin. Based upon survival, we could identify optimal cutoff points for CD4+ T cells in pediatric (age of <20 years) patients: 248 × 106/L and 420 × 106/L at days 100 and 180, respectively; and in adult (age of >20 years) patients: 104 × 106/L and 115 × 106/L at days 100 and 180, respectively. In adults, day-100 CD4 count was associated with overall survival (OS), progression-free survival (PFS), and TRM but not relapse, incidence of infections, or chronic GVHD. Similarly, CD4 counts above the cutoff point at day 180 in adults were associated with improved OS, PFS, and TRM but no other outcomes. No clinical associations for CD4 counts were identifiable in pediatric patients. These findings underscore the importance of tailoring transplant strategies for adults to optimize immune recovery and improve patient outcomes.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3502-3517"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954765","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":"Completion of phase 2b trial of etranacogene dezaparvovec gene therapy in patients with hemophilia B over 5 years.","authors":"Annette von Drygalski, Esteban Gomez, Adam Giermasz, Giancarlo Castaman, Nigel S Key, Susan U Lattimore, Frank W G Leebeek, Wolfgang A Miesbach, Michael Recht, Paul E Monahan, Sandra Le Quellec, Steven W Pipe","doi":"10.1182/bloodadvances.2024015291","DOIUrl":"10.1182/bloodadvances.2024015291","url":null,"abstract":"<p><strong>Abstract: </strong>Etranacogene dezaparvovec (CSL222, formerly AMT-061) is a recombinant adeno-associated virus serotype 5 (AAV5) vector containing the highly active factor IX (FIX) Padua variant controlled by a liver-specific promoter. This phase 2b, open-label, single-dose, single-arm, multicenter trial evaluated the efficacy and safety of etranacogene dezaparvovec. Three adult participants with severe or moderately severe hemophilia B (FIX ≤2%) and AAV5-neutralizing antibodies received a single IV dose (2 × 1013 genome copies per kg) of etranacogene dezaparvovec. The primary end point of FIX activity ≥5 IU/dL at 6 weeks was met (mean, 30.6 IU/dL). Secondary end points included bleed frequency, FIX concentrate use, and adverse events. Here, we report the end-of-study 5-year outcomes. After administration, mean (range) FIX activity increased to 40.8 IU/dL (31.3-50.2) at year 1 and was maintained at 45.7 IU/dL (39.0-51.2) at year 5. Mean annualized bleeding rate (all bleeds) was 0.14 for the cumulative follow-up period years 0 to 5. Two participants had 5 bleed-free years after treatment. Per protocol, 1 participant received episodic FIX replacement therapy after treatment for elective surgeries, 2 bleeding episodes, and 2 single self-administered infusions for unreported reasons. All participants discontinued and remained free of FIX prophylaxis. During the 5-year study period, there were no clinically significant elevations in liver enzymes, requirement for steroids, FIX inhibitor development, thrombotic complications, or late-emergent safety events in any participant. Five years after administration, etranacogene dezaparvovec was effective in adults with hemophilia B with a favorable safety profile. Participants are eligible to participate in an extension study (ClinicalTrials.gov identifier: NCT05962398) for 10-year additional follow-up. This trial was registered at www.clinicaltrials.gov as #NCT03489291.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3543-3552"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794667","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":"2025 ASH ISTH NBDF WFH monitoring report on the 2021 clinical guidelines on the diagnosis and management of von Willebrand disease.","authors":"Paula D James, Veronica H Flood, Nathan T Connell","doi":"10.1182/bloodadvances.2025016512","DOIUrl":"10.1182/bloodadvances.2025016512","url":null,"abstract":"<p><strong>Abstract: </strong>The American Society of Hematology (ASH), International Society on Thrombosis and Haemostasis (ISTH), National Hemophilia Foundation (NHF; now National Bleeding Disorders Foundation), and World Federation of Hemophilia (WFH) 2021 guidelines on the diagnosis and management of von Willebrand disease (VWD) included 11 recommendations on the diagnosis of VWD and 12 recommendations on the management of VWD, the most common inherited bleeding disorder. We describe the results of a review of the 2021 guidelines by the clinical co-chairs of the guideline panels requested by ASH to inform decision-making about the need for and timing of a guideline revision. An updated MEDLINE and Embase search applied the same terms as the ASH ISTH NHF WFH 2021 guidelines limited to studies from 2020 to 30 July 2024 (diagnosis) or 24 July 2024 (management). For the diagnosis of VWD, 432 studies were identified and underwent title and abstract review, with 17 undergoing full text review, and for the management of VWD, 288 studies were identified and underwent title and abstract review, with 37 undergoing full text review, to determine whether the data would change the strength or directionality of the existing recommendation or merit development of a new recommendation. Based on this review, the clinical co-chairs noted that none of the reviewed studies would change the direction or strength of the existing guideline recommendations. There will be continued monitoring of the ASH ISTH NHF WFH 2021 guidelines on the diagnosis and management of VWD to evaluate whether there is sufficient new evidence to warrant additional revisions.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3553-3555"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954409","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":"Longitudinal analysis of gut microbiome and metabolome correlates of response and toxicity with idecabtagene vicleucel.","authors":"Satabdi Saha, Lubna Rehman, Abdur Rehman, Faezeh Darbaniyan, Donna M Weber, Melody Becnel, Mahmoud Gaballa, Sheeba K Thomas, Hans C Lee, Chia-Chi Chang, Reetakshi Arora, Meghan Menges, Salvatore Corallo, Marco L Davila, Frederick L Locke, Mark R Tanner, Sattva S Neelapu, Elizabeth J Shpall, Christopher R Flowers, Robert Z Orlowski, Robert R Jenq, Michael D Jain, Christine Peterson, Doris K Hansen, Neeraj Y Saini, Krina K Patel","doi":"10.1182/bloodadvances.2024014476","DOIUrl":"10.1182/bloodadvances.2024014476","url":null,"abstract":"<p><strong>Abstract: </strong>Increasing evidence suggests that the gut microbiome may influence the responses and toxicities associated with chimeric antigen receptor T-cell (CAR-T) therapy. We conducted whole-genome shotgun sequencing on stool samples (N = 117) collected at various times from patients with multiple myeloma (n = 33) who underwent idecabtagene vicleucel (ide-cel) anti-B-cell maturation antigen CAR-T therapy. We observed a significant decrease in bacterial diversity after ide-cel infusion, along with significant differences in the bacterial composition linked to therapy response and toxicities. Specifically, we found significant enrichment of Flavonifractor plautii, Bacteroides thetaiotaomicron, Blautia fecis, and Dysosmobacter species in ide-cel responders. A notable finding was the link of major microbiome disruption, defined as the presence of dominant specific taxa (>35% prevalence), and increased facultative pathobionts, like Enterococcus, with ide-cel toxicities, especially cytokine release syndrome (CRS). Patients with genus dominance in baseline samples had a higher incidence of grade 2 or higher CRS at 46.2% than those without genus dominance (11.1%; P = .043). In addition, network analysis and mass spectrometric assessment of stool metabolites revealed important associations and pathways, such as F plautii being linked to increased indole metabolites and pathways in responders. Our findings uncovered novel microbiome associations between ide-cel responses and toxicities that may be useful for developing modalities to improve CAR-T outcomes.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3429-3440"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810602","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":"Atezolizumab consolidation in patients with high-risk diffuse large B-cell lymphoma in complete remission after R-CHOP.","authors":"Marcel Nijland, Djamila E Issa, Johanna A A Bult, Dries Deeren, Gerjo A Velders, Marten R Nijziel, Yorick Sandberg, Vibeke Vergote, Margriet Oosterveld, Rob Fijnheer, Rolf E Brouwer, Rinske S Boersma, Kalung Wu, Laurens Nieuwenhuizen, Joost S P Vermaat, Roel J W van Kampen, Wim E Terpstra, Sylvia Snauwaert, Marjolein W van der Poel, Eva de Jongh, Marc F Durian, Leonie Strobbe, Aart Beeker, Alain Gadisseur, Roos S van Rijn, Otto Visser, Jeanette K Doorduijn, Tjeerd J F Snijders, Matthijs H Silbermann, Daphne de Jong, Martine Chamuleau, Rogier Mous, Hilde Jalving, Heleen Visser-Wisselaar, Sonja Jansen van de Bergh, Gerben J C Zwezerijnen, Edwin Bremer, Mirian Brink, Arjan Diepstra, Dana A Chitu, Harry R Koene, Josée M Zijlstra","doi":"10.1182/bloodadvances.2024015226","DOIUrl":"10.1182/bloodadvances.2024015226","url":null,"abstract":"<p><strong>Abstract: </strong>The risk of relapse among high-risk patients with diffuse large B-cell lymphoma (DLBCL) in complete metabolic remission (CMR) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy is 20% to 25%. Here, we evaluated whether consolidation with the programmed cell death ligand 1 checkpoint inhibitor atezolizumab could reduce the relapse risk. In this phase 2, open-label trial, patients with DLBCL with an International Prognostic Index (IPI) score of ≥3 and CMR after R-CHOP received 1200 mg atezolizumab every 3 weeks for 18 cycles. The primary end point was disease-free survival (DFS) at 2 years, with the aim of improving it to 89% compared to historical 79%. Secondary end points included overall survival (OS) and safety (Common Terminology Criteria for Adverse Events version 4.0). Analyses were on an intention-to-treat principle. Of 109 patients, 65% completed treatment. The cohort was 59% males, with 63% having high-intermediate risk IPI scores. At a median follow-up of 36.4 months, 15 relapses occurred (median, 8.2 months). The 2-year DFS was 87.9% (90% confidence interval [CI], 81.5-92.1), and the 2-year OS was 96.3% (90% CI, 91.7-98.3), meeting the primary objective. Treatment with salvage chemotherapy resulted in 10 of 13 patients achieving a second CMR. OS was significantly better among atezolizumab-treated patients than in a population-based matched control cohort from the Netherlands Cancer Registry. Adverse events (AEs) affected 79% of patients, with 18% developing immune-related AEs, including 4.5% grade 3 to 4. Atezolizumab consolidation significantly improved DFS in high-risk patients with DLBCL compared to historical cohorts. OS was significantly better than a population-based control cohort. These findings warrant further validation and assessment of immune checkpoint inhibitors as consolidation strategy in DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT03463057.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3530-3539"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979008","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":"Prognostic significance of monocytic-like phenotype in patients with AML treated with venetoclax and azacytidine.","authors":"Lin-Pierre Zhao, Typhaine Dumas-Rivero, Lauren Barette, Lorea Aguinaga, Arij Cheffai, Clémentine Chauvel, Reinaldo Dal Bello, Emmanuel Raffoux, Emmanuelle Clappier, Matthieu Duchmann, Pierre Fenaux, Pierre Lemaire, Stephanie Mathis, Marie Sébert, Lionel Adès, Raphaël Itzykson","doi":"10.1182/bloodadvances.2024015734","DOIUrl":"10.1182/bloodadvances.2024015734","url":null,"abstract":"<p><strong>Abstract: </strong>The prognostic impact of monocytic differentiation in patients with acute myeloid leukemia (AML) receiving venetoclax (Ven) and azacitidine (Aza) remains unclear. In a prospective cohort of 86 newly diagnosed patients with AML treated with Ven-Aza, we used multiparametric flow cytometry (MFC) to define monoblasts as AML blasts coexpressing ≥2 monocytic markers (CD4, CD36, and CD64) per European LeukemiaNet (ELN) guidelines. Patients with higher monoblasts/CD45+ proportions had lower complete response rates (odds ratio, 0.24; P = .005) and significantly shorter overall survival (OS; 4.0 vs 14.9 months; P = .003). A ≥10% monoblasts/CD45+ threshold, identified via maximally selected rank statistics, stratified patients into monoblasthigh (≥10%) and monoblastlow (<10%) groups. MFC reclassified 20% of French-American-British (FAB) non-M4/5 and 15% of FAB M4/5 cases into monoblasthigh and monoblastlow groups, respectively. Multivariable analysis confirmed monoblasthigh status as an independent adverse prognostic factor for OS (hazard ratio [HR], 1.95; P = .023), with a particularly strong impact in ELN 2024 favorable-risk patients (HR, 2.81; P = .024). Our findings highlight monocytic differentiation, assessed via MFC, as a key predictor of Ven-Aza resistance and poor survival, independent of genetic classification. Given its availability in routine diagnostics, MFC-based monocytic assessment could improve AML risk stratification and treatment decisions in patients eligible for less intensive therapies. This trial was registered at www.clinicaltrials.gov as #NCT05326919.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3556-3565"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981522","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":"NTRK1-rearranged histiocytosis: clinicopathologic and molecular features.","authors":"Rivers Fragneau, Sylvie Fraitag, Paul G Kemps, Zofia Hélias-Rodzewicz, Somak Roy, Benjamin Bonsang, Allison L Bartlett, Subhra Dhar, Martin Jankofsky, Jozef Zlocha, Karel Svojgr, Lenka Krsková, Andrica C H de Vries, Robert M Verdijk, Jan A M van Laar, Roos J Leguit, Philippe Drabent, Eric D Carlsen, Jonhan Ho, Arivarasan D Karunamurthy, Mariarita Santi, Marie-Laure Jullié, Florian Babor, Robert Lorsbach, Astrid G S van Halteren, Sébastien Héritier, Eli L Diamond, Benjamin H Durham, Ashish R Kumar, Arunaloke Bhattacharya, Julien Haroche, Jean Donadieu, Arndt Borkhardt, Jennifer L Picarsic, Jean-François Emile","doi":"10.1182/bloodadvances.2025016167","DOIUrl":"10.1182/bloodadvances.2025016167","url":null,"abstract":"<p><strong>Abstract: </strong>Non-Langerhans cell histiocytoses are a diverse group of histiocytic diseases. Different entities are defined based on clinical, histopathologic, and/or molecular characteristics. This study aimed to define NTRK-rearranged histiocytosis. Through international collaboration, we investigated 50 cases of histiocytosis with pan-tropomyosin receptor kinase (pan-TRK) expression and/or in-frame NTRK rearrangement. We also analyzed 45 control xanthogranulomas using pan-TRK immunohistochemistry and targeted RNA sequencing. Slides were centrally reviewed; clinical and molecular data were collected. The 50 cases comprised 30 children and 20 adults with a median age of 11.5 years (range, 0-73 years) and a male predominance (64%). Most patients (88%) had disease limited to the skin, including a single skin nodule in 41 patients and multiple skin lesions in 3 others. Four newborns presented with skin lesions, hepatomegaly, and thrombocytopenia that required transfusions. The 2 remaining patients had life-threatening lesions of the brain or bronchus. All cases displayed xanthogranuloma histology, often including foamy histiocytes and Touton giant cells. Histiocytes stained positive for pan-TRK in 50 of 50 cases, whereas all 45 control xanthogranulomas without in-frame NTRK fusions stained negative. NTRK1 fusion partners included IRF2BP2 (23/46), TPM3 (12/46), SQSTM1 (3/46), PRDX1 (3/46), NPM1 (2/46), LMNA (2/46), and ARHGEF2 (1/46). Clinical outcomes were favorable, including spontaneous disease regression in 3 of 4 newborns with systemic disease, and rapid clinical response in both patients with a brain or bronchial tumor treated with the TRK inhibitor larotrectinib. This study advances the molecular characterization of histiocytoses and may guide the diagnosis and personalized treatment of patients.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3617-3628"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975641","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":"Untangling profiles of postthrombotic syndrome using unsupervised machine learning.","authors":"Aaron F J Iding, Vincent Ten Cate, Hugo Ten Cate, Philipp S Wild, Arina J Ten Cate-Hoek","doi":"10.1182/bloodadvances.2025015829","DOIUrl":"10.1182/bloodadvances.2025015829","url":null,"abstract":"<p><strong>Abstract: </strong>Postthrombotic syndrome (PTS) is a chronic condition that can develop after deep vein thrombosis (DVT) and is diagnosed using the Villalta scale. This study applied unsupervised machine learning to investigate the heterogeneity of PTS among patients and within the Villalta scale. In 818 patients from the IDEAL DVT study, clustering identified 4 clinical profiles: (1) younger patients with provoked DVT, (2) women with joint pain, (3) men with isolated popliteal DVT, and (4) older men with diabetes and femoral vein involvement. Clustering of Villalta items revealed a distinction between signs and symptoms. Sign scores increased with older age, male sex, higher body mass index (BMI), and DVT extent, whereas symptom scores increased with younger age, female sex, higher BMI, and provoked DVT. Residual venous obstruction was significantly associated with the sign score (odds ratio, 1.18 per point) but not the symptom score. Quality of life was related to the symptom score more than the sign score. At 6 months, sign and symptom scores differed significantly across profiles, especially between profile 1 and 4, because the former had most symptoms (41% vs 21% ≥ 3; P < .001), whereas the latter had most signs (18% vs 34% ≥ 3; P = .004]). After 2 years, symptoms decreased in profile 1 but increased in profile 4. Other profiles showed intermediate scores over time. These findings suggest that reappraising the PTS scoring system to distinguish its dimensions would enable more personalized risk prediction and prevention. This trial was registered at www.ClinicalTrials.gov as #NCT01429714.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3631-3641"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630195","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":"Evaluating the long-term benefits of hydroxyurea in pediatric sickle cell anemia.","authors":"Paul George, Grace Kalmus, Peter A Lane, Wilbur Lam, Joseph Lipscomb, David Howard","doi":"10.1182/bloodadvances.2024015564","DOIUrl":"10.1182/bloodadvances.2024015564","url":null,"abstract":"<p><strong>Abstract: </strong>Hydroxyurea is the primary disease-modifying medication for sickle cell anemia (SCA), but its long-term effects, particularly how these effects change over time, are not well understood. This study aimed to quantify the effects of hydroxyurea on clinical and laboratory outcomes in children with SCA over a prolonged period of use. We conducted a quasi-experimental study using contemporary difference-in-differences and dynamic event study analyses on a longitudinal cohort of 2147 children with SCA (hemoglobin SS or hemoglobin SSβ0, HbSS/HbSβ0) from 2010 to 2021. The primary outcomes included emergency department (ED) visits per year, hospital days per year, and annual average hemoglobin concentration. Hydroxyurea use was associated with fewer ED visits per year (average treatment effect on the treated [ATT], -0.36 visit per year; 95% confidence interval [CI], -0.57 to -0.16) and fewer hospital days per year (ATT, -0.84 d/y; 95% CI, -1.51 to -0.17) with sustained effects over time. On average, the hemoglobin concentration increased with hydroxyurea use (ATT, 0.56 g/dL; 95% CI, 0.39-0.73), but the sustained effect was observed only among the subgroup with laboratory markers of good adherence. This study demonstrates that hydroxyurea has sustained clinical benefits in reducing ED visits and hospital days across years of use in children with SCA. These findings provide perspective for clinicians and families regarding the long-term efficacy of hydroxyurea in pediatric SCA management and underscore the importance of ongoing adherence counseling to optimize clinical benefit. Furthermore, this study design provides a methodological framework for rigorously and causally evaluating other SCA-specific treatments, such as stem cell transplant and gene therapy, in real-world settings.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3585-3593"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970597","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}