Blood advances最新文献

{"title":"Thalassemia carriers exhibit reduced expression of the receptor for the malarial parasite Plasmodium vivax on erythrocytes.","authors":"Renliang Huang, Xinze Li, Zhe Lu, Jing Xu, Dan Lin, Yunxue Fu, Yan Liang, Frank Petersen, Xuexia Li, Qiaomiao Zhou, Xinhua Yu","doi":"10.1182/bloodadvances.2024014792","DOIUrl":"10.1182/bloodadvances.2024014792","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1738-1741"},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000312","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":"Teclistamab for Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma and Renal Impairment.","authors":"Danai Dima, Aimaz Afrough, Utkarsh Goel, Ariel Grajales-Cruz, Jack Khouri, Kelley Julian, Oren Pasvolsky, Rahul Banerjee, Beatrice Razzo, Christopher J Ferreri, Mariola Alejandra Vazquez Martinez, James A Davis, Aishwarya Sannareddy, Omar Castaneda Puglianini, Shahzad Raza, Andrew J Portuguese, Mahmoud R Gaballa, Masooma Rana, Alex Lieberman-Cribbin, Shaun DeJarnette, Rebecca Gonzalez, Anna Chen, Megan M Herr, Lakha Mikkilineni, Hitomi Hosoya, Evguenia Ouchveridze, Gurbakhash Kaur, Adriana C Rossi, Leyla Shune, Faiz Anwer, Yi Lin, Shambavi Richard, Douglas W Sborov, Rachid C Baz, Alfred Garfall, Hans C Lee, Larry D Anderson, Andrew J Cowan, Krina K Patel, Peter M Voorhees, Surbhi Sidana, Doris K Hansen, Shebli Atrash, Sandra P Susanibar-Adaniya","doi":"10.1182/bloodadvances.2025016059","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016059","url":null,"abstract":"<p><p>Outcomes of bispecific antibodies in patients with renal impairment (RI) are not well-characterized given the exclusion of these patients from clinical trials. Herein, we evaluated patients with relapsed/refractory multiple myeloma and RI treated with standard-of-care teclistamab. RI was defined as creatinine clearance (CrCl) <40mL/min. CrCl <30mL/min or dialysis dependence were defined as severe RI. Of the 384 included patients, 81 (21%) had RI, including 45 (18%) with severe RI, and 18 (5%) on dialysis. Patients with RI were more likely to be older (median age 71 vs. 67 years, p=0.002), and have a higher median number of prior lines of therapy (7 vs. 6, p=0.04). Rates and severity of cytokine release syndrome (51% vs. 59%, grade ≥3: 1.2% vs. 1%) and immune effector cell-associated neurotoxicity syndrome (16% vs. 13%; grade ≥3: 2.5% vs 2.6%) were similar in patients with and without RI, respectively. Patients with RI had higher baseline and day-30 post-teclistamab grade ≥3 anemia and grade ≥3 thrombocytopenia. Renal function did not worsen after teclistamab initiation in patients with RI outside of the context of disease progression. Overall response rate (52% vs. 56%, p=0.61) and survival outcomes (median progression-free survival: 4.6 vs. 6.5 months; p=0.62) were comparable in patients with and without RI, respectively, after a median follow-up of 9.9 months. No differences in overall survival or non-relapse mortality were noted. Our findings suggest that treatment with teclistamab is feasible in patients with RI including those on dialysis, with a similar safety and efficacy profile to patients without RI.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810606","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":"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":"https://doi.org/10.1182/bloodadvances.2024015291","url":null,"abstract":"<p><p>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, multi-center trial evaluated the efficacy and safety of etranacogene dezaparvovec. All participants (n=3) were adults, had severe or moderately severe hemophilia B (FIX ≤2%), and AAV5 neutralizing antibodies. Participants received a single intravenous dose (2×1013 genome copies/kg) of etranacogene dezaparvovec. The primary endpoint of FIX activity ≥5 IU/dL at 6 weeks was met (mean 30.6IU/dL). Secondary endpoints included bleed frequency, FIX concentrate use, and adverse events. Here we report the end-of-study 5-year outcomes. Post-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 ABR (all bleeds) was 0.14 for the cumulative follow-up period Years 0-5. Two participants had 5 bleed-free years post-treatment. Per protocol, one participant received episodic FIX replacement therapy post-treatment for elective surgeries, two bleeding episodes, and two 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 post-administration, etranacogene dezaparvovec was effective in adults with hemophilia B with a favorable safety profile. Participants are eligible to participate in an extension study (NCT05962398) for 10-years additional follow-up. ClinicalTrials.gov Identifier: NCT03489291.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discrepancy between original and adapted ASH VTE guidelines: same clinical evidence but different recommendations.","authors":"Suely Meireles Rezende, Ignacio Neumann, Benjamin Djulbegovic","doi":"10.1182/bloodadvances.2025016102","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016102","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794668","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":"Immunological Consequences of CAR T-Cell Therapy - Analysis of Infectious Complications and Immune Reconstitution.","authors":"Andreas Riedel, Laurent Phely, Stefan Hug, Philipp Faustmann, Jan Schröder, Britta Besemer, Anna M Paczulla Stanger, Christoph Faul, Claudia Lengerke, Jan Frederic Weller, Wolfgang Andreas Bethge","doi":"10.1182/bloodadvances.2024015346","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015346","url":null,"abstract":"<p><p>Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated remarkable efficacy in treating relapsed and refractory (R/R) B-cell neoplasms, such as diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Despite its success, the long-term effects and sequelae of CAR T cells on the immune system remain underexplored. This study presents a one-year follow-up analysis of 52 patients (42 with R/R DLBCL and 10 with R/R MM) treated with anti-CD19- and BCMA-targeted CAR T-cells, focusing on immune reconstitution and infectious complications. Our findings show that CAR T-cell therapy leads to profound depletion of B- and T-cells. In particular, CD4+ T-cells and CD19+ B-cells exhibited impaired regeneration post-treatment. Infections were more frequent during the first 30 days. In the short-term follow up, density of infections within 100 days at risk was 1.8 in DLBCL patients and 4.6 in MM patients, with bacterial infections predominating in this early period after CAR-T infusion. Additionally, we observed a shift to viral infections in the long-term follow-up, alongside with a decline in infection density to 0.1 in DLBCL patients and 0.4 infections per 100 days at risk in MM patients, respectively. Severe cytokine release syndrome (CRS) was associated with a higher risk of late-onset infections. These findings highlight the importance of close monitoring and prophylactic measures in CAR T-cell therapy patients to reduce infection risks and enhance immune recovery.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794670","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":"Distinct routes of clonal progression in SF3B1-mutant myelodysplastic syndromes.","authors":"Martina Sarchi, Courtnee A Clough, Anna Gallì, Cristina Picone, Beatrice Ferrari, Edie I Crosse, Laura D Baquero Galvis, Claudia Fiducioso, Nelli Aydinyan, J Philip Creamer, Sara Pozzi, Elisabetta Molteni, Chiara Elena, Robert K Bradley, Luca Malcovati, Sergei Doulatov","doi":"10.1182/bloodadvances.2024014965","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014965","url":null,"abstract":"<p><p>Myelodysplastic syndromes (MDS) are clonal stem cell disorders driven by heterogeneous genetic alterations leading to variable clinical course. MDS with splicing factor SF3B1 mutations is a distinct subtype with a favorable outcome. However, selected co-mutations induce poor prognosis and how these genetic lesions cooperate in human hematopoietic stem and progenitor cells (HSPCs) during disease progression is still unclear. Here, we integrated clinical and molecular profiling of patients with SF3B1 mutations with gene editing of primary and iPSC-derived human HSPCs to show that high-risk co-mutations impart distinct effects on lineage programs of SF3B1-mutant HSPCs. Secondary RUNX1 or STAG2 mutations were clinically associated with advanced disease and reduced survival. However, RUNX1 and STAG2 mutations induced opposing regulation of myeloid transcriptional programs and differentiation in SF3B1-mutant HSPCs. Moreover, high-risk RUNX1 and STAG2, but not low-risk TET2, mutations expanded distinct SF3B1-mutant HSPC subpopulations. These findings provide evidence that progression from low- to high-risk MDS involves distinct molecular and cellular routes depending on co-mutation patterns.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794669","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":"Platelet activating histone/antihistone IgG complexes in anti-PF4 negative thrombosis and thrombocytopenia syndrome.","authors":"Max Esefeld, Stefan Handtke, Rainer Kaiser, Leo Nicolai, Lea Di Fina, Dario Rossaro, Jan Wesche, Justina Rath, Ann-Christin Wienrich, Till Hoffmann, Lukas Harasser, Clemens Feistritzer, Lorin Loacker, Kourosh Lotfi, Margareta Holmström, Jovan Antovic, Leif Steil, Uwe Volker, Lena Ulm, Karsten Becker, Nils-Olaf Hübner, Andreas Greinacher, Thomas Thiele","doi":"10.1182/bloodadvances.2024015076","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015076","url":null,"abstract":"<p><p>Thrombosis and Thrombocytopenia syndromes (TTS) describe immune mediated thrombotic adverse reactions following vaccination against Covid-19. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a well-known sub-entity of TTS, caused by adenovirus vector-based vaccines. VITT is mediated by anti-platelet factor 4 (PF4) IgG-antibodies, activating platelets via Fc-gamma IIa receptors (FcgRIIa). We describe clinical and serological features of 18 patients with anti-PF4/heparin ELISA negative TTS in temporal relationship to mRNA-based Covid-19 vaccination. Symptoms began at a median of 7 (range 1-61) days after vaccination. Patients showed thrombocytopenia (59,000/µl, 0-127,000/µl); petechiae (n=7), venous thromboembolism (n=11), arterial thrombosis (n=6), disseminated intravascular coagulation (n=1), and combined arterial and venous thromboses (n=1). Twelve sera induced FcgRIIa dependent and caspase independent procoagulant activation of platelets indicated by phosphatidylserine exposure and CD62P expression. We found histones precipitated with IgG fractions of TTS sera and antibodies binding to histones were found in 8/12 platelet-activating sera. Ex vivo generated histone/anti-histone IgG complexes strongly activated platelets via FcgRIIa, whereas anti-histone-IgG alone did not. Platelet autoantibodies were detected in 7/12 sera targeting GPIIb/IIIa (n=5); GPIb/IX (n=5) and GPIa/IIa (n=3). However, sera containing platelet anti-GPIIb/IIIa autoantibodies activated also platelets from a Glanzmann patient, making it unlikely that these autoantibodies are causative for platelet activation. Finally, 2/114 healthy vaccinees developed anti-histone antibodies after mRNA-based Covid-19 vaccination. Our data indicate a new sub-entity of TTS associated with platelet activating histone/anti-histone IgG complexes. Further studies are warranted to characterize the biological and clinical role of post-mRNA-based vaccination anti-histone antibodies. SeCo, NCT04370119.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779177","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":"Triaging Acute Chest Syndrome Clinical Decision-Making Using Bedside SaO2/FiO2 Ratio.","authors":"Austin Wesevich, Megan Elizabeth Woelkers, Ayodeji Adegunsoye, Adam J Wesevich, Mark J Ratain, Gabrielle Lapping-Carr","doi":"10.1182/bloodadvances.2024015139","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015139","url":null,"abstract":"<p><p>Acute chest syndrome (ACS) severity is inconsistently defined and its clinical course difficult to predict. This retrospective observational study evaluated the utility of the ratio of the pulse oximetry oxygen saturation to the fraction of inspired oxygen (SaO2/FiO2) in adult patients with ACS and its association with the clinical outcome of intensive care unit (ICU) transfer. Across all ACS hospitalizations at a tertiary medical center from 2017-2021, we characterized the SaO2/FiO2 ratio at 3 timepoints: emergency department (ED) presentation, diagnosis with ACS, and antibiotic initiation. Of the 227 hospitalizations identified, 54% were female, mean age was 29, 70% had Hgb SS, and 9% had obesity. While ICU transfer was not strongly associated with the SaO2/FiO2 ratio at ED presentation (AUC 0.59), it was strongly associated with the SaO2/FiO2 ratio at ACS diagnosis (AUC 0.73) and antibiotic initiation (AUC 0.74). Given the highest sensitivity at ACS diagnosis, a diagnostic SaO2/FiO2 cutoff of 310 was proposed for triaging likely ICU transfer (sensitivity 63%, specificity 82%, aOR 8.94, 95% CI 2.12-37.6, adjusted HR 4.86, 95% CI 1.91-12.4) with models adjusting for obesity, lung disease, and blood counts. This cutoff corresponds to an SpO2 below 90% on 2 L/min nasal cannula support. We propose using the SaO2/FiO2 ratio cutoff of 310 prospectively as a simple bedside triage tool for adult patients with sickle cell disease hospitalized with ACS to be transferred to a higher level of care.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779240","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":"Maintenance therapy with romidepsin after autologous stem-cell transplant for peripheral T-cell lymphoma.","authors":"Niloufer Khan, Parastoo B Dahi, Farhad Khimani, Andrei Shustov, Mazyar Shadman, Jia Ruan, Alison J Moskowitz, Andrew D Zelenetz, Ariela Noy, David J Straus, Pamela R Drullinsky, Audrey M Hamilton, Anita Kumar, Craig S Sauter, Gunjan L Shah, Matthew J Matasar, Esther Drill, Theresa Davey, Helen Hancock, Nivetha Ganesan, Natasha Galasso, Koen Van Besien, Sergio A Giralt, Steven M Horwitz","doi":"10.1182/bloodadvances.2024014263","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014263","url":null,"abstract":"<p><p>Patients with peripheral T-cell lymphomas (PTCL) have suboptimal outcomes. Autologous hematopoietic stem cell transplant (AHCT) is a therapeutic strategy for patients in first complete or partial remission (CR1 or PR1), with median intent to treat progression-free survival (PFS) of 36-48%. Romidepsin is a histone deacetylase inhibitor used for treatment of relapsed/refractory PTCL. We present the first multicenter study to evaluate PFS of patients receiving maintenance therapy with romidepsin after AHCT. Twenty-six patients transplanted in CR1 or PR1 were evaluable for the primary endpoint of 2-year PFS. An exploratory cohort enrolled pts either transplanted in or after CR/PR2 (n=5) or with high-risk histologies (n=2). Patients underwent AHCT with carmustine, etoposide, cytarabine and melphalan (BEAM) conditioning. Romidepsin 14 mg/m2 started at days 42-80 post AHCT every other week until six months post AHCT, every three weeks between six months and one year post AHCT, and every four weeks between one - two years post AHCT. PFS was estimated by Kaplan-Meier. 47 patients consented; 13 did not receive romidepsin. With median progression-free follow up of 32 months (range 24-36 months), 15 out of the first 25 patients in Cohort 1 were progression-free after 2 years. Estimated 2-year PFS was 62% (45-83%, 95% CI). Across cohorts, 5 patients required dose reduction. Most common toxicities were fatigue (n=24, 73%), decreased platelets (n=16, 48%) and anemia (n=16, 48%). While the study did not meet its desired primary efficacy endpoint, maintenance romidepsin was feasible with a favorable estimated 2-year PFS of 62%, relative to historical data. Clinicaltrials.gov NCT01908777.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779167","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":"Characteristics and Outcomes of Patients with Double Refractory and Double Exposed Chronic Lymphocytic Leukemia.","authors":"James T Yoon, Yinglu Zhou, Mariia Mikhaleva, Daniel Sungchul Choi, Stacey M Fernandes, Philippe Armand, Amy C Bessnow, Jennifer L Crombie, David C Fisher, Eric D Jacobsen, Caron A Jacobson, Austin I Kim, Ann S LaCasce, Reid W Merryman, Oreofe O Odejide, Erin M Parry, David A Qualls, Christine E Ryan, Aswin Sekar, Jacob D Soumerai, Jon E Arnason, Svitlana Tyekucheva, Matthew S Davids, Jennifer R Brown, Inhye E Ahn","doi":"10.1182/bloodadvances.2025016006","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016006","url":null,"abstract":"<p><p>We analyzed the characteristics and outcomes of 95 patients with chronic lymphocytic leukemia (CLL) post-Bruton tyrosine kinase inhibitor (BTKi) and B-cell lymphoma 2 inhibitor (BCL2i) failure. To clearly distinguish sensitivity and resistance to the targeted treatment classes, we defined double refractory (DR) CLL when progressive disease occurred during active treatment with a BTKi and a BCL2i given sequentially or in combination and double exposed (DE) disease when treatment with either or both of these agents was discontinued due to reasons other than progression. Thirty (31.6%) patients had DR CLL and 65 (63.2%) had DE CLL. The DR group more frequently had unmutated IGHV (97%), TP53 aberration (73%), and BTK mutations (59%) than the DE group (75%, 46%, and 27%, respectively). The median number of total lines of therapy was 6 for DR and 3 for DE. Nearly all (97%) DR patients required subsequent therapy after developing DR CLL. The most commonly used treatment was non-covalent BTKis (34%), followed by concurrent covalent BTKi and BCL2i (28%) and CD19 chimeric antigen receptor-modified T cells (24%). Treatment for DE CLL was less frequently observed (26%). Median overall survival (OS) was 2.2 years once DR developed despite frequent initial responses to non-covalent BTKis or cellular therapy in the cohort. Patients with DE CLL demonstrated favorable survival (median OS not reached) and durable response to subsequent therapy.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779166","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}