Blood advances最新文献

{"title":"ALLG APML5: bioavailability and safety of oral arsenic trioxide assessed during consolidation therapy for APL.","authors":"Harry J Iland, John Reynolds, Alan V Boddy, Hayley B Schultz, Liane Khoo, Shaun Fleming, Steven W Lane, Nicholas Weber, Robin Gasiorowski, Tasman Armytage, Rosemary Harrup, Anne-Marie Watson, Peter Tan, Robin Filshie, Fiona Kwok, William Stevenson, Sam Yuen, Ashley P Ng, Leesa Rowley, Paula Marlton, Andrew H Wei","doi":"10.1182/bloodadvances.2024015397","DOIUrl":"10.1182/bloodadvances.2024015397","url":null,"abstract":"<p><strong>Abstract: </strong>The prognosis for patients with acute promyelocytic leukemia (APL) has improved dramatically since the introduction of all-trans retinoic acid and IV arsenic trioxide (ATO). However, ATO administration requires daily infusions over several months, representing an onerous burden for hospitals and patients. We evaluated the bioavailability of a novel encapsulated oral ATO formulation in patients with APL in first complete remission during standard-of-care consolidation. After a pilot study exploring the likely oral dose requirement, total arsenic pharmacokinetics were evaluated in 20 patients after both IV and oral ATO 0.15 mg/kg per day, with exposure to oral ATO restricted to the first week in 2 of 4 ATO cycles. The primary end point was bioequivalence of area under the curve from 0 to 24 hours (AUC0-24), with bioequivalence of maximum concentration achieved (Cmax) as the key secondary end point. The 90% confidence intervals (CIs) around point estimates of the geometric means of the oral-to-IV ratios for AUC0-24 and Cmax were compared with bioequivalence limits specified by the European Medicines Agency (0.80-1.25). The estimated oral-to-IV ratios and 90% CIs for AUC0-24 in whole blood and plasma were 0.993 (0.954-1.034) and 1.030 (0.977-1.087) respectively; data for Cmax also satisfied bioequivalence requirements. Exploratory studies of arsenic species in plasma showed bioequivalence for AUC0-24 with As(III) (oral-to-IV ratio, 0.966 [0.879-1.063]). The adverse event profiles of oral and IV ATO were comparable for cycles commencing with the IV and oral formulations. In conclusion, this novel oral ATO formulation is bioequivalent with IV ATO and offers a convenient alternative for patients with APL. This trial was registered at www.anzctr.org.au as #ACTRN12616001022459.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1476-1484"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058167","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":"Targeting SDOH inequities in hematologic malignancies.","authors":"Joanna M Robles, Kimberly Montez","doi":"10.1182/bloodadvances.2024015741","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015741","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 6","pages":"1472-1473"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699714","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":"Health care systems as determinants of outcomes in multiple myeloma: final results from the Latin American MYLACRE study.","authors":"Vania Hungria, Rafael Gaiolla, Kenny Galvez, Guillermina Remaggi, Natalia Schutz, Rosane Bittencourt, Angelo Maiolino, Guillermo Quintero-Vega, Maria Silvana Cugliari, Walter Moises Tobias Braga, Carolina Colaco Villarim, Edvan Crusoe, Alicia Ines Enrico, Gaston Caiero, Jandey Bigonha, Fernanda Lemos Moura, Jair Figueroa, Claudia Lucia Sossa Melo, Milton Lombana, Huiling Pei, Mariana Fernandez, Jaqueline Saes, Damila Cristina Trufelli","doi":"10.1182/bloodadvances.2024013838","DOIUrl":"10.1182/bloodadvances.2024013838","url":null,"abstract":"<p><strong>Abstract: </strong>Although systemic therapy for multiple myeloma (MM) has evolved considerably over the past 2 decades, state-of-the-art treatment is not uniformly available in Latin America. In some countries, disparities between the public and private sectors in clinical presentation, access to novel agents, and transplantation are striking, with the public sector lagging. We conducted a multicenter, observational study of patients with MM in 5 Latin American countries (Argentina, Brazil, Colombia, Mexico, and Panama). We enrolled patients aged ≥18 years diagnosed with MM between January 2016 and June 2021, using data collected between May 2019 and June 2022. We categorized institutions as \"public\" when primarily funded by federal or local government, and \"private\" when financed mostly or completely by other sources. We analyzed 1029 patients, 1021 of whom could be classified into public (n = 339) and private (n = 682) institutions. These 2 groups differed in many respects, with patients from the latter having better baseline prognostic features (including eligibility to transplantation) and receiving combinations of immunomodulatory drugs and proteasome inhibitors, as well as anti-CD38 antibodies, more frequently than patients from public institutions. Among 960 patients with complete data for this analysis, the median overall survival was 44.6 months in public institutions and 53.3 months in private institutions (hazard ratio, 0.84; 95% confidence interval, 0.67-1.04; P = .109). Our results indicate diagnostic and therapeutic shortcomings in the management of MM in Latin America, with important gaps in patient profile, treatment patterns and long-term outcomes between public and private institutions. This trial was registered at www.clinicaltrials.gov as #NCT03955900.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1293-1302"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827480","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":"G3BP1::CSF1R: a new and actionable gene fusion in acute megakaryoblastic leukemia.","authors":"Xi Luo, Chi-Keung Cheng, Hoi-Yun Chan, Kam-Tong Leung, Chi-Kong Li, Nellie Yuk-Fei Chung, Herbert Augustus Pitts, Ke Tian, Yuet-Fong Kam, Margaret H L Ng","doi":"10.1182/bloodadvances.2024014354","DOIUrl":"10.1182/bloodadvances.2024014354","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1286-1292"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869381","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":"Characterization of the phenotypic consequences of the Duffy-null genotype.","authors":"Micah R Hysong, Megan M Shuey, Jennifer E Huffman, Paul Auer, Alexander Reiner, Laura M Raffield","doi":"10.1182/bloodadvances.2024014399","DOIUrl":"10.1182/bloodadvances.2024014399","url":null,"abstract":"<p><strong>Abstract: </strong>A wealth of research focused on African American populations has connected rs2814778-CC (\"Duffy-null\") to decreased neutrophil (neutropenia) and leukocyte counts (leukopenia). Although it has been proposed that this variant is benign, prior studies have shown that the misinterpretation of Duffy-null-associated neutropenia and leukopenia can lead to unnecessary bone marrow biopsies, inequities in cytotoxic and chemotherapeutic treatment courses, underenrollment in clinical trials, and other disparities. To investigate the phenotypic correlates of Duffy-null status, we conducted a phenome-wide association study across >1400 clinical conditions in All of Us, the Vanderbilt University Medical Center's Biobank, and the Million Veteran Program. This reveals that Duffy-null status is only reproducibly associated with changes in white blood cell count and not with any disease outcomes. Moreover, we find that Duffy-null-associated neutropenia is on average less severe than other neutropenia cases in All of Us. We also show that this genotype is present in considerable frequencies in All of Us populations that are genetically similar to African (68%) and Middle Eastern (14%) 1000 Genomes/Human Genome Diversity Project reference populations as well as those who identify with >1 race (12%), as Pacific Islander (7%), and as Hispanic (5%). Furthermore, we find that race is not an accurate predictor of Duffy-null status or associated benign neutropenia. Our research suggests that broad genetic screening of rs2814778 across all populations could provide a more robust and accurate understanding of white blood cell count and mitigate resulting health disparities.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1452-1462"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000471","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":"Clinical use of measurable residual disease in adult ALL: recommendations from a panel of US experts.","authors":"Nicholas J Short, Ibrahim Aldoss, Daniel J DeAngelo, Marina Konopleva, Jessica Leonard, Aaron C Logan, Jae Park, Bijal Shah, Wendy Stock, Elias Jabbour","doi":"10.1182/bloodadvances.2024015441","DOIUrl":"10.1182/bloodadvances.2024015441","url":null,"abstract":"<p><strong>Abstract: </strong>Measurable residual disease (MRD) is a powerful predictor of clinical outcomes in acute lymphoblastic leukemia (ALL). In addition to its clear prognostic importance, MRD information is increasingly used in clinical decision algorithms to guide therapeutic interventions. Although it is well established that achievement of MRD-negative remission is an important end point of ALL therapy, the prognostic and therapeutic implications of MRD in an individual patient are influenced by both disease-related factors (eg, cytomolecular risk) and assay-related factors (eg, sensitivity, specimen source, and timing of assessment), which add complexity to MRD-guided treatment decisions. In this review, we discuss the data supporting the use of MRD assessment in adult ALL and how this information can rationally inform clinical decisions, including selection of patients for MRD-directed therapies or allogeneic hematopoietic stem cell transplantation. We also discuss important interpretative challenges related to novel high sensitivity next-generation sequencing-based MRD assays, which are becoming increasingly used in clinical practice.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1442-1451"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032283","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":"Predicting risk in Hodgkin lymphoma for research and clinical practice.","authors":"Ruohui Chen, Leo I Gordon","doi":"10.1182/bloodadvances.2024015742","DOIUrl":"10.1182/bloodadvances.2024015742","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 6","pages":"1387-1389"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623608","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":"Cost-effectiveness of Voncento prophylaxis vs on-demand treatment in von Willebrand disease in the United Kingdom.","authors":"Michele Wilson, Giancarlo Castaman, Will Thomas, Carolyn Millar, Ginés Escolar, Wolfgang Miesbach, Cheryl McDade, Radovan Tomic, Songkai Yan","doi":"10.1182/bloodadvances.2024014376","DOIUrl":"10.1182/bloodadvances.2024014376","url":null,"abstract":"<p><strong>Abstract: </strong>von Willebrand factor (VWF) concentrates may be required for on-demand treatment (ODT) or long-term prophylaxis (LTP) in von Willebrand disease (VWD). This study assesses the cost-effectiveness of LTP compared with ODT in patients with VWD treated with Voncento in the United Kingdom. A Markov structure was developed to estimate the quality-adjusted life years (QALYs) and costs of VWD treatment over a lifetime horizon. Treatment options included ODT or LTP. For both options, we assumed plasma-derived VWF/factor VIII 2.4:1 (Voncento) as the VWF product used. Clinical parameters were obtained from published literature and Voncento's summary characteristics. Utility weights were obtained from published literature. Costs (in 2021 GBP [£]) and outcomes were discounted annually by 3.5%. Sensitivity analyses were conducted. Three baseline annual bleed rate (ABR) scenarios (11, 26.5, and 39.6) were considered. In the base-case analyses, Voncento LTP resulted in lower costs (-£831 206) and greater QALYs (6.14) vs ODT. Savings were primarily due to reductions in product use required (-£529 571) and bleed-related other medical costs (-£301 352). Compared with ODT, LTP also resulted in 322.52 fewer major bleeds and 515.68 fewer minor bleeds over a lifetime horizon. Probabilistic sensitivity analyses showed dominance in 96.12% of simulations and cost-effectiveness in 97.68% of simulations. For the 39.6 ABR scenario also, LTP was dominant compared with ODT. Results suggest that Voncento LTP is more effective and cost saving than ODT in the United Kingdom for patients with VWD with higher ABR. Prophylaxis for patients with frequent bleeds is likely to be a cost-saving and effective strategy.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1312-1319"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852830","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":"Combination therapies of porcupine inhibition with ruxolitinib, ibrutinib, or belumosudil in murine sclerodermatous GVHD.","authors":"Xuezhi Hong, Yanhua Xiao, Liyan Xu, Lichong Shen, Ranjana Neelagar, Veda Devakumar, Thuong Trinh-Minh, Minrui Liang, Aleix Rius Rigau, Yun Zhang, Yi-Nan Li, Clara Dees, Andrea-Hermina Györfi, Daniel Wolff, Wolfgang Herr, Georg Schett, Jörg H W Distler, Alexandru-Emil Matei","doi":"10.1182/bloodadvances.2024014387","DOIUrl":"10.1182/bloodadvances.2024014387","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1261-1266"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944918","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":"Relationship between additional mutations at diagnosis and treatment response in patients with essential thrombocythemia.","authors":"Carole Mosnier, Sarah Bellal, Laurane Cottin, Françoise Boyer, Sandrine Lemoine, Amélie Bachelot, Joris Argentin, Bertille Pawlicki, Marie-Christine Copin, Rébecca Jouanneau-Courville, Anaïs Malinge, Jérémie Riou, Mathilde Hunault-Berger, Valérie Ugo, Corentin Orvain, Damien Luque Paz","doi":"10.1182/bloodadvances.2024014791","DOIUrl":"10.1182/bloodadvances.2024014791","url":null,"abstract":"<p><strong>Abstract: </strong>Patients with essential thrombocythemia (ET) have a chronic evolution with a risk of hematologic transformation associated with a dismal outcome. Because patients with resistance or intolerance have adverse prognosis, it is important to identify which patient will respond to first-line treatment. We, therefore, aim to describe the association between additional mutations and response to first-line treatment in patients with ET. In this retrospective study, we analyzed the molecular landscape of 121 ET patients first-line treated with hydroxyurea (HU; n = 86) or pegylated interferon (peg-IFN; n = 35). Patients undergoing peg-IFN therapy were younger and had higher proportion of low and very low risk of thrombosis recurrence. A total of 62 patients (51%) had ≥1 additional mutations at diagnosis. At 12 months of treatment, 75 patients (62%) achieved complete response (CR), 37 (31%) partial response, and 7 (6%) no response. The presence of at least 1 additional mutation at diagnosis was associated with not achieving CR (hazard ratio [HR], 0.65; P = .038), whereas treatment with peg-IFN was associated with higher CR (HR, 2.00; P = .002). The number of additional mutations at diagnosis was associated with hematologic progressions (P < .0001). None of the patients receiving peg-IFN therapy progressed to myelofibrosis, whereas 16 of 86 patients (19%) treated with HU developed secondary myelofibrosis. In conclusion, our results suggest that the presence of at least 1 additional mutation at diagnosis is associated with failure to achieve CR and also with an increased risk of hematologic evolution.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"1303-1311"},"PeriodicalIF":7.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000310","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}