BloodPub Date : 2024-10-31DOI: 10.1182/blood.2024025896
Silvia Deaglio
{"title":"Toward a new paradigm for CLL treatment.","authors":"Silvia Deaglio","doi":"10.1182/blood.2024025896","DOIUrl":"10.1182/blood.2024025896","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"144 18","pages":"1849-1850"},"PeriodicalIF":21.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543589","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}
BloodPub Date : 2024-10-31DOI: 10.1182/blood.2023021789
Alison J Moskowitz, Robert N Stuver, Steven M Horwitz
{"title":"Current and upcoming treatment approaches to common subtypes of PTCL (PTCL, NOS; ALCL; and TFHs).","authors":"Alison J Moskowitz, Robert N Stuver, Steven M Horwitz","doi":"10.1182/blood.2023021789","DOIUrl":"10.1182/blood.2023021789","url":null,"abstract":"<p><strong>Abstract: </strong>The treatment of common nodal peripheral T-cell lymphomas (PTCLs), including PTCL, not otherwise specified (PTCL, NOS), anaplastic large-cell lymphomas, and T-follicular helper lymphomas, is evolving. These entities are currently treated similarly with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) for CD30-negative diseases, or brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (CHP) for CD30-positive diseases, followed by consolidation with autologous stem cell transplantation in the first remission. Ongoing improvements in PTCL classification, identification of predictive biomarkers, and development of new targeted agents will lead to more specific therapies that address the unique biologic and clinical properties of each entity. For example, widespread efforts focused on molecular profiling of PTCL, NOS is likely to identify distinct subtypes that warrant different treatment approaches. New agents, such as EZH1/2 and JAK/STAT pathway inhibitors, have broadened treatment options for relapsed or refractory diseases. Furthermore, promising strategies for optimizing immune therapy for PTCL are currently under investigation and have the potential to significantly alter the therapeutic landscape. Ongoing frontline study designs incorporate an understanding of disease biology and drug sensitivities and are poised to evaluate whether newer-targeted agents should be incorporated into frontline settings for various disease entities. Although current treatment strategies lump most disease entities together, future treatments will include distinct strategies for each disease subtype that optimize therapy for individuals. This movement toward individualized therapy will ultimately lead to dramatic improvements in the prognosis of patients with PTCL.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1887-1897"},"PeriodicalIF":21.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671286","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}
BloodPub Date : 2024-10-31DOI: 10.1182/blood.2023021787
Javeed Iqbal, Giorgio Inghirami, Wing C Chan
{"title":"New insights into the biology of T-cell lymphomas.","authors":"Javeed Iqbal, Giorgio Inghirami, Wing C Chan","doi":"10.1182/blood.2023021787","DOIUrl":"10.1182/blood.2023021787","url":null,"abstract":"<p><strong>Abstract: </strong>Peripheral T-cell lymphomas (PTCLs) encompass a heterogeneous group of postthymic T-cell lymphomas with >30 distinct subtypes associated with varied clinicopathological features. Unfortunately, the overall survival of the major PTCL subtypes is dismal and has not improved for decades; thus, there is an urgent unmet clinical need to improve diagnosis, therapies, and clinical outcomes. The diagnosis is often challenging, requiring a combinatorial evaluation of clinical, morphologic, and immunophenotypic features. PTCL pathobiology is difficult to investigate due to enormous intertumor and intratumor heterogeneity, limited tissue availability, and the paucity of authentic T-cell lymphoma cell lines or genetically faithful animal models. The application of transcriptomic profiling and genomic sequencing has markedly accelerated the discovery of new biomarkers, molecular signatures, and genetic lesions, and some of the discoveries have been included in the revised World Health Organization or International Consensus Classification. Genome-wide investigations have revealed the mutational landscape and transcriptomic profiles of PTCL entities, defined the cell of origin as a major determinant of T-cell lymphoma biology, and allowed for the refinement of biologically and clinically meaningful entities for precision therapy. In this review, we prioritize the discussion on common nodal PTCL subtypes together with 2 virus-associated T-cell and natural killer cell lymphomas. We succinctly review normal T-cell development, differentiation, and T-cell receptor signaling as they relate to PTCL pathogenesis and biology. This review will facilitate a better biological understanding of the different PTCL entities and their stratification for additional studies and target-directed clinical trials.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1873-1886"},"PeriodicalIF":21.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104258","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":"A predictive model for therapy failure in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy.","authors":"Xiaoshuai Zhang, Bingcheng Liu, Jian Huang, Yanli Zhang, Na Xu, Robert Peter Gale, Weiming Li, Xiaoli Liu, Huanling Zhu, Ling Pan, Yunfan Yang, Hai Lin, Xin Du, Rong Liang, Chunyan Chen, Xiaodong Wang, Guohui Li, Zhuogang Liu, Yanqing Zhang, Zhenfang Liu, Jianda Hu, Chunshui Liu, Fei Li, Wei Yang, Li Meng, Yanqiu Han, Li'e Lin, Zhenyu Zhao, Chuanqing Tu, Caifeng Zheng, Yanliang Bai, Zeping Zhou, Suning Chen, Huiying Qiu, Lijie Yang, Xiuli Sun, Hui Sun, Li Zhou, Zelin Liu, Danyu Wang, Jianxin Guo, Liping Pang, Qingshu Zeng, Xiaohui Suo, Weihua Zhang, Yuanjun Zheng, Xiaojun Huang, Qian Jiang","doi":"10.1182/blood.2024024761","DOIUrl":"10.1182/blood.2024024761","url":null,"abstract":"<p><strong>Abstract: </strong>Although tyrosine kinase inhibitor (TKI) therapy has markedly improved the survival of people with chronic-phase chronic myeloid leukemia (CML), 20% to 30% of people still experienced therapy failure. Data from 1955 consecutive patients with chronic-phase CML diagnosed by the European LeukemiaNet recommendations from 1 center receiving initial imatinib or a second-generation (2G) TKI therapy were interrogated to develop a clinical prediction model for TKI-therapy failure. This model was subsequently validated in 3454 patients from 76 other centers. Using the predictive clinical covariates associated with TKI-therapy failure, we developed a model that stratified patients into low-, intermediate- and high-risk subgroups with significantly different cumulative incidences of therapy failure (P < .001). There was good discrimination and calibration in the external validation data set, and the performance was consistent with that of the training data set. Our model had the better prediction discrimination than the Sokal and European Treatment and Outcome Study long-term survival scores, with the greater time-dependent area under the receiver-operator characteristic curve values and a better ability to redefine the risk of therapy failure. Our model could help physicians estimate the likelihood of initial imatinib or 2G TKI-therapy failure in people with chronic-phase CML.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1951-1961"},"PeriodicalIF":21.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751057","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}
BloodPub Date : 2024-10-31DOI: 10.1182/blood.2023021791
Philippe Armand
{"title":"Introduction to a review series on peripheral T-cell lymphomas: salutary complexity?","authors":"Philippe Armand","doi":"10.1182/blood.2023021791","DOIUrl":"https://doi.org/10.1182/blood.2023021791","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"144 18","pages":"1847-1848"},"PeriodicalIF":21.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543587","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}
BloodPub Date : 2024-10-31DOI: 10.1182/blood.2024024487
Jing Nie, Chunmeng Wang, Liangtao Zheng, Yang Liu, Chengcheng Wang, Yixin Chang, Yudi Hu, Bing Guo, Yuting Pan, Qingming Yang, Xueda Hu, Weidong Han
{"title":"Epigenetic agents plus anti-PD-1 reprogram the tumor microenvironment and restore antitumor efficacy in Hodgkin lymphoma.","authors":"Jing Nie, Chunmeng Wang, Liangtao Zheng, Yang Liu, Chengcheng Wang, Yixin Chang, Yudi Hu, Bing Guo, Yuting Pan, Qingming Yang, Xueda Hu, Weidong Han","doi":"10.1182/blood.2024024487","DOIUrl":"10.1182/blood.2024024487","url":null,"abstract":"<p><strong>Abstract: </strong>DNA methyltransferase inhibitor decitabine plus anti-programmed cell death 1 (DP) therapy was effective in relapsed/refractory classic Hodgkin lymphoma (cHL). However, a subset of patients experienced primary resistance or relapse/progression after DP therapy. In this study, we evaluated the efficacy and safety of a triplet regimen consisting of the histone deacetylase inhibitor chidamide, decitabine, and anti-PD-1 camrelizumab (CDP) in 52 patients who previously received DP therapy. CDP treatment was well tolerated and resulted in an objective response rate of 94% (95% confidence interval [CI], 84-99), with 50% (95% CI, 36-64) of patients achieving complete response (CR). Notably, all patients who were recalcitrant to previous DP treatment exhibited therapeutic responses after CDP therapy, although their CR rate was lower than patients responsive to prior DP. Overall, the median progression-free survival was 29.4 months. Through single-cell RNA sequencing of pretreatment and on-treatment cHL tumor biopsy samples, we observed the heterogeneity of rare malignant Hodgkin Reed/Sternberg (HRS)-like cells. The classical CD30+ HRS-like cells interacted with abundant immunosuppressive IL21+CD4+ T helper cells, forming a positive feedback loop that supported their survival. While the CD30- HRS-like cell population showed potential resistance to anti-PD-1 immunotherapy. CDP treatment promoted the activation of diverse tumor-reactive CD8+ T cells and suppressed the proliferation of IL21+CD4+ T cells by inhibiting STAT1/3 signaling, thereby alleviating their immunosuppressive effects. These findings provide insights into the cHL microenvironment that contributes to anti-PD-1 resistance and highlight the therapeutic effectiveness of dual epi-immunotherapy in overcoming immunotherapy resistance. This trial was registered at www.clinicaltrials.gov as #NCT04233294.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1936-1950"},"PeriodicalIF":21.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878346","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}
BloodPub Date : 2024-10-31DOI: 10.1182/blood.2024024631
Othman Al-Sawaf, Sandra Robrecht, Can Zhang, Stefano Olivieri, Yi Meng Chang, Anna Maria Fink, Eugen Tausch, Christof Schneider, Matthias Ritgen, Karl-Anton Kreuzer, Liliya Sivchev, Carsten Utoft Niemann, Anthony Schwarer, Javier Loscertales, Robert Weinkove, Dirk Strumberg, Allanah Kilfoyle, Beenish S Manzoor, Dureshahwar Jawaid, Nnadozie Emechebe, Jacob Devine, Michelle Boyer, Eva D Runkel, Barbara Eichhorst, Stephan Stilgenbauer, Yanwen Jiang, Michael Hallek, Kirsten Fischer
{"title":"Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study.","authors":"Othman Al-Sawaf, Sandra Robrecht, Can Zhang, Stefano Olivieri, Yi Meng Chang, Anna Maria Fink, Eugen Tausch, Christof Schneider, Matthias Ritgen, Karl-Anton Kreuzer, Liliya Sivchev, Carsten Utoft Niemann, Anthony Schwarer, Javier Loscertales, Robert Weinkove, Dirk Strumberg, Allanah Kilfoyle, Beenish S Manzoor, Dureshahwar Jawaid, Nnadozie Emechebe, Jacob Devine, Michelle Boyer, Eva D Runkel, Barbara Eichhorst, Stephan Stilgenbauer, Yanwen Jiang, Michael Hallek, Kirsten Fischer","doi":"10.1182/blood.2024024631","DOIUrl":"10.1182/blood.2024024631","url":null,"abstract":"<p><strong>Abstract: </strong>In the CLL14 study, patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). Progression-free survival (PFS) was the primary end point. Key secondary end points included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS), and rates of adverse events. Patient reported outcomes of time until definitive deterioration (TUDD) in quality of life (QoL) were analyzed. At a median observation time of 76.4 months, PFS remained superior for Ven-Obi compared with Clb-Obi (median, 76.2 vs 36.4 months; hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.31-0.52; P < .0001). Likewise, TTNT was longer after Ven-Obi (6-year TTNT, 65.2% vs 37.1%; HR, 0.44; 95% CI, 0.33-0.58; P < .0001). In the Ven-Obi arm, presence of del(17p), unmutated immunoglobulin heavy-chain variable region, and lymph node size of ≥5 cm were independent prognostic factors for shorter PFS. The 6-year OS rate was 78.7% in the Ven-Obi and 69.2% in the Clb-Obi arm (HR, 0.69; 95% CI, 0.48-1.01; P = .052). A significantly longer TUDD in global health status/QoL was observed in the Ven-Obi than in the Clb-Obi arm (median, 82.1 vs 65.1 months; HR, 0.70; 95% CI, 0.51-0.97). Follow-up-adjusted second primary malignancies incidence rates were 2.3 and 1.4 per 1000 patient-months in the Ven-Obi and Clb-Obi arm, respectively. The sustained long-term survival and QoL benefits support the use of 1-year fixed-duration Ven-Obi in CLL. This trial was registered at www.ClinicalTrials.gov as #NCT02242942.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1924-1935"},"PeriodicalIF":21.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854765","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}
BloodPub Date : 2024-10-31DOI: 10.1182/blood.2024024649
Charlotte M Thomas, M Khalid F Salamat, Florian Almela, Jillian K Cooper, Kaetan Ladhani, Mark E Arnold, Daisy Bougard, Olivier Andréoletti, E Fiona Houston
{"title":"Longitudinal detection of prion infection in preclinical sheep blood samples compared using 3 assays.","authors":"Charlotte M Thomas, M Khalid F Salamat, Florian Almela, Jillian K Cooper, Kaetan Ladhani, Mark E Arnold, Daisy Bougard, Olivier Andréoletti, E Fiona Houston","doi":"10.1182/blood.2024024649","DOIUrl":"10.1182/blood.2024024649","url":null,"abstract":"<p><strong>Abstract: </strong>Variant Creutzfeldt-Jakob disease (vCJD) is a devastating disease caused by transmission of bovine spongiform encephalopathy to humans. Although vCJD cases are now rare, evidence from appendix surveys suggests that a small proportion of the United Kingdom population may be infected without showing signs of disease. These \"silent\" carriers could present a risk of iatrogenic vCJD transmission through medical procedures or blood/organ donation, and currently there are no validated tests to identify infected asymptomatic individuals using easily accessible samples. To address this issue, we evaluated the performance of 3 blood-based assays in a blinded study, using longitudinal sample series from a well-established large animal model of vCJD. The assays rely on amplification of misfolded prion protein (PrPSc; a marker of prion infection) and include real-time quaking-induced conversion (RT-QuIC), and 2 versions of protein misfolding cyclic amplification (PMCA). Although diagnostic sensitivity was higher for both PMCA assays (100%) than RT-QuIC (61%), all 3 assays detected prion infection in blood samples collected 26 months before the onset of clinical signs and gave no false-positive results. Parallel estimation of blood prion infectivity titers in a sensitive transgenic mouse line showed positive correlation of infectivity with PrPSc detection by the assays, suggesting that they are suitable for detection of asymptomatic vCJD infection in the human population. This study represents, to our knowledge, the largest comparison to date of preclinical prion detection in blood samples from a relevant animal model. The outcomes will guide efforts to improve early detection of prion disease and reduce infection risks in humans.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1962-1973"},"PeriodicalIF":21.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035215","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}
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