American Journal of Hematology最新文献

{"title":"Clinico-Genomic Interrogation of Secondary-Type Acute Myeloid Leukemia: Response and Outcomes to Contemporary Therapies","authors":"Jayastu Senapati, Sanam Loghavi, Jennifer Marvin-Peek, Guillermo Garcia-Manero, Tapan M. Kadia, Gautam Borthakur, Naval Daver, Nicholas J. Short, Nitin Jain, Ghayas C. Issa, Fadi Haddad, Danielle Hammond, Kelly Chien, Guillin Tang, Beenu Thakral, Guillermo Montalban-Bravo, Naveen Pemmaraju, Alexandre Bazinet, Mahesh Swaminathan, Sherry Pierce, Hussein A. Abbas, Patrick Reville, Uday Popat, Elizabeth Shpall, Richard Champlin, Elias Jabbour, Farhad Ravandi, Hagop M. Kantarjian, Courtney D. DiNardo","doi":"10.1002/ajh.27628","DOIUrl":"https://doi.org/10.1002/ajh.27628","url":null,"abstract":"Ontogeny of acute myeloid leukemia (AML) provides prognostic information, however closer interrogation with respect to AML characteristics, genomics, and various treatments are warranted. We defined untreated clinical secondary (CS) AML as AML with a diagnosis of antecedent myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MDS-MPN) without exposure to hypomethylating agents or chemotherapy; genomic secondary (GS) AML included patients with myelodysplasia related cytogenetics (MRC) or myelodysplasia related mutations (MRM) without a known antecedent myeloid neoplasm or prior chemo-radiotherapy for non-myeloid neoplasms. Among newly diagnosed AML patients classified as untreated CS-AML (<i>n</i> = 133) or GS-AML (<i>n</i> = 389), median relapse-free survival (RFS) (11.9 vs. 12.4 months, <i>p</i> = 0.36) and overall survival (OS) (11.6 vs. 14.4 months, <i>p</i> = 0.75) were similar. No difference in RFS and OS between these groups treated with low-intensity therapy (LIT) and venetoclax regimens was seen, but both were inferior to <i>de novo</i> (DN) AML without secondary-type genomics (pure DN-AML). GS-AML defined by the presence of only MRM had superior OS compared with MRM ± MRC with LIT+ venetoclax therapy (RFS 19.5 vs. 6.8 months [<i>p</i> &lt; 0.01] and OS 29.6 vs. 8.4 [<i>p</i> &lt; 0.01]) and had similar RFS (29.8 months, <i>p</i> = 0.48) and OS (32.0 months, <i>p</i> = 0.48) to pure DN-AML treated with LIT+ venetoclax. On multivariate analysis in patients treated with LIT+ venetoclax, untreated CS-AML (vs. GS-AML), adverse cytogenetics and ELN 2024 adverse-risk disease (mutated <i>TP53</i>) were associated with higher hazard of death. Adverse cytogenetics was the strongest prognostic variable predicting survival. Mutation-driven genomic ontogeny of newly diagnosed AML with MRM appears less prognostic than cytogenetic-driven ontogeny with venetoclax-based therapy.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"62 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371586","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":"It's More Than Complex: Further Insights Into TP53 in MPN","authors":"Nico Gagelmann, Nicolaus Kröger","doi":"10.1002/ajh.27632","DOIUrl":"https://doi.org/10.1002/ajh.27632","url":null,"abstract":"TP53 in MPN.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"59 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371502","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":"A Transfusion Reaction due to Anti-ER5 in a Hyposplenic β0 Thalassemia Major Patient","authors":"Arun Thomas, Kirstin Lund, Viviene Ballon, Barbara J. Bain","doi":"10.1002/ajh.27623","DOIUrl":"https://doi.org/10.1002/ajh.27623","url":null,"abstract":"<div>\u0000<figure>\u0000<div><picture>\u0000<source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/64345587-126f-4f18-a7ea-5159cf375f43/ajh27623-gra-0001-m.jpg\"/><img alt=\"image\" data-lg-src=\"/cms/asset/64345587-126f-4f18-a7ea-5159cf375f43/ajh27623-gra-0001-m.jpg\" loading=\"lazy\" src=\"/cms/asset/7647a287-3036-4ce2-b99b-6c8df39a4ef7/ajh27623-gra-0001-m.png\" title=\"image\"/></picture><p></p>\u0000</div>\u0000</figure>\u0000</div>\u0000<div>\u0000<figure>\u0000<div><picture>\u0000<source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/c47c6691-0665-4106-8ede-5889d765e677/ajh27623-gra-0002-m.jpg\"/><img alt=\"image\" data-lg-src=\"/cms/asset/c47c6691-0665-4106-8ede-5889d765e677/ajh27623-gra-0002-m.jpg\" loading=\"lazy\" src=\"/cms/asset/39c9b4bc-4add-4eab-a443-28a96038c75c/ajh27623-gra-0002-m.png\" title=\"image\"/></picture><p></p>\u0000</div>\u0000</figure>\u0000</div>\u0000<p>A 6-year-old boy of Libyan ethnic origin was referred to pediatric hematology 3 months after entering the United Kingdom as a refugee. The child was known to have thalassemia major. His parents were first cousins. He had previously been transfused every 4 weeks, received chelation therapy and had been splenectomized. More recently, transfusion requirement had increased to every 2 weeks and he had developed post-transfusion hemoglobinuria, which was not ameliorated by corticosteroids. He had not been transfused since arriving in the United Kingdom and his hemoglobin concentration (Hb) was 72 g/L. Anti-c and anti-E were present together with a panagglutinating antibody directed at the high frequency antigen, ER5. It was not possible to source ER5-negative blood and he was therefore transfused with Rh-typed red cells under cover of intravenous immunoglobulin, methylprednisolone, and eculizumab. Transfusion led to an initial rise of Hb to 96 g/L but, despite the precautions taken, by 3 days the Hb had fallen to 65 g/L. His mother reported that following the transfusion his urine had again become red.</p>\u0000<p>Post-transfusion his blood film (both images, ×100 objective) showed hypochromic red cells, target cells, Howell–Jolly bodies, Pappenheimer bodies, schistocytes, alpha chain inclusions within hypochromic erythrocytes (upper image), and nucleated red blood cells. In addition to the evidence of thalassemia and hyposplenism, there were also considerable numbers of spherocytes, indicating a transfusion reaction. The direct antiglobulin test was positive for immunoglobulin G (+). Molecular analysis showed homozygosity for β⁰ thalassemia, specifically NM_000518.4: c93-22_95del p.? In addition, there was homozygosity for the Xmn1 (−158) polymorphism of the <i>HBG2</i> gene, which leads to some increase in hemoglobin F synthesis.</p>\u0000<p>ER5 is a recently recognized, high incidence antigen, antibodies to which can cause hemolytic disease of the fetus and newborn [<span>1</span>]. Future management of the child will be fraught with problems.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"123 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257965","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":"Outcomes of Relapsed or Refractory Diffuse Large B-Cell Lymphoma Treated With R-GemOx: A Multicenter Cohort Study","authors":"Samuel Yamshon, Jean L. Koff, Melissa C. Larson, Brad S. Kahl, Carla Casulo, Izidore S. Lossos, Sara Haddadi, Michele Stanchina, Dai Chihara, Amy Ayers, Thomas M. Habermann, Yucai Wang, Arushi Khurana, Grzegorz S. Nowakowski, Tanner W. Reicks, Umar Farooq, Brian K. Link, Jonathon B. Cohen, Peter Martin, Jia Li, Ashwini Shewade, Connie Lee Batlevi, Andrea Lo-Rossi, David Fox, Anthony Masaquel, Yong Mun, James R. Cerhan, Christopher R. Flowers, Matthew J. Maurer, Loretta J. Nastoupil","doi":"10.1002/ajh.27630","DOIUrl":"https://doi.org/10.1002/ajh.27630","url":null,"abstract":"Rituximab, gemcitabine, and oxaliplatin (R-GemOx) is a commonly used chemoimmunotherapy regimen for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but there are limited real-world data. In a multicenter retrospective study from a cohort of eight US academic centers (LEO CReWE), we evaluated 183 patients with R/R DLBCL and high-grade B cell lymphoma treated with R-GemOx, including subgroups treated without intent for consolidation with autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T cell therapy (<i>n</i> = 100), those utilizing R-GemOx as a bridge to ASCT or CAR T (<i>n</i> = 83), and those aged 70 and older (<i>n</i> = 71). Overall response rates (ORRs) for all patients treated with R-GemOx were 45% with a complete response (CR) rate of 29%. The median event-free survival (EFS) was 2.3 months, and the median overall survival (OS) was 13.5 months. Patients receiving R-GemOx without intent for ASCT or CAR T had ORR and CR rates of 33% and 18%, respectively, with median EFS and OS of 2.0 and 9.5 months, respectively. Patients receiving R-GemOx as a bridge to ASCT or CAR T had ORR and CR rates of 57% and 36%, respectively, with median EFS and OS of 3.5 and 17.4 months, respectively. Patients receiving R-GemOx aged 70 and older had ORR and CR rates of 53% and 33%, respectively, with median EFS and OS of 2.2 and 13.9 months, respectively. These data provide a benchmark for R-GemOx in the rapidly evolving landscape of R/R DLBCL therapies.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"23 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258064","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":"Multicenter Prospective First-Line Helicobacter Pylori Eradication for Localized Gastric “Pure” Diffuse Large B-Cell Lymphoma","authors":"Li-Tzong Chen, Kun-Huei Yeh, Chung-Wu Lin, Tsang-En Wang, Ming-Chung Wang, Chin-Fu Hsiao, Chieh-Chang Chen, Jyh-Ming Liou, Hsiu-Po Wang, Ming-Feng Wei, Hsiao-Wei Lee, Chia-Tung Shun, Tsang-Wu Liu, Hwei-Fang Tien, Ming-Shiang Wu, Sung-Hsin Kuo, Ann-Lii Cheng","doi":"10.1002/ajh.27624","DOIUrl":"https://doi.org/10.1002/ajh.27624","url":null,"abstract":"&lt;p&gt;Our exploratory study evaluated the efficacy of first-line &lt;i&gt;Helicobacter pylori&lt;/i&gt; eradication (HPE) therapy on early-stage (stage IE/IIE1) &lt;i&gt;Helicobacter pylori&lt;/i&gt; (HP)-positive gastric diffuse large B-cell lymphomas (DLBCLs) without histological evidence of mucosa-associated lymphoid tissue (MALT) (“pure” DLBCLs). The study showed that 11 of 16 (68.8%) patients achieved complete remission (CR) after successful HPE and remained lymphoma-free after a median follow-up of 7.7 years [&lt;span&gt;1&lt;/span&gt;]. Another study by Tari et al. demonstrated that 4 of 15 (26.7%) patients with gastric “pure” DLBCLs who received first-line antibiotic treatment achieved CR and remained lymphoma-free after a median follow-up of 7–100 months [&lt;span&gt;2&lt;/span&gt;]. Additionally, Ferrieri et al. studied 16 patients with gastric DLBCLs, of whom, 11 had “pure” DLBCLs and five had DLBCLs with histological evidence of MALT (DLBCL[MALT]), who were administered HPE (including clarithromycin, tinidazole or metronidazole, and omeprazole) [&lt;span&gt;3&lt;/span&gt;]. Of these, eight patients achieved CR and three achieved partial remission (PR), with an overall response rate (ORR) of 68.8% after HPE [&lt;span&gt;3&lt;/span&gt;]. Cumulatively, these findings indicate that certain patients with gastric “pure” DLBCLs are responsive to first-line antibiotic therapy and might have a better quality of life because they are not exposed to the conventional immunochemotherapy-related adverse effects. However, prospective studies evaluating patients whose tumors are not limited to the stomach but extend to the perigastric lymph node area are warranted.&lt;/p&gt;\u0000&lt;p&gt;Considering that “pure” DLBCLs of the stomach grow rapidly when the tumors do not respond to first-line HPE, identifying molecular markers that can predict HP independence (the lack of CR of tumors after completing HPE) is necessary. Our previous study showed that in in vitro DLBCL cell lines, B cell activating factor (BAFF) triggered the activation of NF-κB. Furthermore, it caused nuclear translocation of BCL10 by inducing AKT phosphorylation and disrupting the interaction of BCL10 with MALT1 and subsequent complex formation of BCL10 and BCL3 (nuclei translation-related genes) [&lt;span&gt;4&lt;/span&gt;]. Furthermore, in tumor samples from patients with gastric DLBCL(MALT)s who received first-line HPE, BAFF overexpression was significantly associated with the nuclear translocation of BCL10 or NF-κB (p65), and the aforementioned molecules (including BAFF, nuclear BCL10, and nuclear NF-κB (p65)) were significantly correlated with HP independence of the tumor [&lt;span&gt;4&lt;/span&gt;]. In contrast to HP-independent biomarkers, we detected HP-encoded protein cytotoxin-associated gene A (CagA) in tumor samples of patients with gastric MALT lymphomas and DLBCL(MALT)s [&lt;span&gt;5, 6&lt;/span&gt;]. The expression of CagA was more frequent in HP-dependent tumors than in HP-independent tumors of gastric lymphomas [&lt;span&gt;5, 6&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;In March 2015, the National Taiwan University and the","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"42 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192495","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":"Recipient Cells Are the Source of Hematologic Malignancies After Graft Failure and Mixed Chimerism in Adults With SCD","authors":"Mohamed A. E. Ali, Emily M. Limerick, Matthew M. Hsieh, Kalpana Upadhyaya, Xin Xu, Oswald Phang, Jean Pierre Kambala Mukendi, Katherine R. Calvo, Maria Lopez‐Ocasio, Pradeep Dagur, Courtney D. Fitzhugh","doi":"10.1002/ajh.27627","DOIUrl":"https://doi.org/10.1002/ajh.27627","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"55 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192277","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":"Correction to “Secondary-Type Mutations Do Not Impact Prognosis in Acute Myelogenous Leukemia AML With Mutated NPM1”","authors":"","doi":"10.1002/ajh.27629","DOIUrl":"https://doi.org/10.1002/ajh.27629","url":null,"abstract":"<p>Wright MF, Pozdnyakova O, Hasserjian RP, et al., 2022. “Secondary-Type Mutations Do Not Impact Prognosis in Acute Myelogenous Leukemia AML With Mutated <i>NPM1</i>.” <i>American Journal of Hematology</i> 97, no. 12: E462–E465. https://doi.org/10.1002/ajh.26730.</p>\u0000<p>The title should read:</p>\u0000<p>Secondary-type mutations do not impact prognosis in AML with mutated <i>NPM1</i>.</p>\u0000<p>The words “acute myelogenous leukemia” should not appear in the title.</p>\u0000<p>We apologize for this error.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"34 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124329","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":"Differential Clinical and Immunological Impacts of Anti–T-Lymphocyte Globulin (ATLG) vs. Anti-Thymocyte Globulin (ATG) in Preventing Graft-Versus-Host Disease Post-Allogeneic Hematopoietic Stem Cell Transplantation: A Comparative Study","authors":"Anne Beatrice Notarantonio, Stéphane Morisset, Romain Piucco, Michaël Pérès, Laura Boulangé, Alizée Alitcher, Jordan Brouard, Lucile Monchablon, Arnaud Campidelli, Siham El Ouahabi, Charles Guisnel, Charline Moulin, Céline Kicki, Gabrielle Roth-Guepin, Pierre Feugier, Marcelo De Carvalho Bittencourt, Alice Aarnink, Maud D'Aveni-Piney, Sébastien Hergalant, Simona Pagliuca, Marie Thérèse Rubio","doi":"10.1002/ajh.27619","DOIUrl":"https://doi.org/10.1002/ajh.27619","url":null,"abstract":"Both anti-T-lymphocyte globulin (ATLG-Grafalon) and anti-thymocyte globulin (ATG-Thymoglobulin) prevent acute and chronic graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite distinct manufacturing and biological characteristics, the two brands of rabbit anti-lymphocyte globulins have never been compared in a prospective way. In this monocentric study, 114 adult patients transplanted with a matched related or unrelated donor after receiving either ATG (<i>n</i> = 50) or ATLG (<i>n</i> = 64) were included to compare their clinical outcomes and broad immune reconstitution parameters. The use of ATLG, compared with ATG, was associated with a 2-fold reduction in Grade II–IV acute GvHD incidence (Cox HR = 0.29; 95% CI 0.14–0.62, <i>p</i> = 0.006), similar relapse incidence, and improved severe GvHD and relapse-free survival (GRFS) (Cox HR = 0.51; 95% CI 0.29–0.91, <i>p</i> = 0.027). Biologically, reduced IL-15 but increased IL-21 serum concentrations and a significant reduction of PD1+ T cells, mainly across all differentiated stages of CD8+ T cells, were observed in the ATLG group. Immunosequencing of vβ T cell receptor (TCR) repertoires showed similar quantitative characteristics in terms of clonality and diversity across the two groups but different qualitative features, with reduced hyper-expanded T cell clones and higher variability in the distribution of complementarity-determining region 3 (CDR3) lengths in the ATLG group. Altogether, these results suggest that ATLG more effectively regulates alloreactive T cell activation, leading to better prevention of acute GvHD while preserving the graft-versus-leukemia response. These findings led us to initiate a multicentric Phase III randomized trial comparing the two anti-lymphocyte globulins.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"12 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124331","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":"Biology and Management of Acute Myeloid Leukemia With Mutated NPM1","authors":"Evan C. Chen, Shai Shimony, Marlise R. Luskin, Richard M. Stone","doi":"10.1002/ajh.27600","DOIUrl":"https://doi.org/10.1002/ajh.27600","url":null,"abstract":"Mutations in nucleophosmin 1 (<jats:italic>NPM1</jats:italic>) are diseased‐defining genetic alterations encountered in approximately one‐third of cases of acute myeloid leukemia (AML). A mutation in <jats:italic>NPM1</jats:italic> confers a more favorable prognosis; however, clinical outcomes of <jats:italic>NPM1</jats:italic>–mutated AML (<jats:italic>NPM1</jats:italic><jats:sup>mut</jats:sup> AML) are diverse due to the heterogeneity of disease biology, patient characteristics, and treatment received. Research over the last two decades has dramatically expanded our understanding of the biology of <jats:italic>NPM1</jats:italic><jats:sup>mut</jats:sup> AML and led to the development of new therapeutic approaches and strategies for monitoring measurable residual disease (MRD). Here, we review <jats:italic>NPM1</jats:italic><jats:sup>mut</jats:sup> AML with a practical focus on the current treatment landscape, the role of MRD in guiding management, and emerging therapies, including menin inhibitors.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"6 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083756","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":"2025 Clinical Trials Update on Hemophilia, VWD, and Rare Inherited Bleeding Disorders","authors":"Debbie Jiang, Michael Wang, Allison P. Wheeler, Stacy E. Croteau","doi":"10.1002/ajh.27602","DOIUrl":"https://doi.org/10.1002/ajh.27602","url":null,"abstract":"Clinical trial programs for inherited bleeding disorders feature an array of innovative prophylaxis options: engineered clotting factor concentrates, FVIIIa mimetics, gene therapies, and biologics to bolster thrombin generation (rebalancing agents). Increasingly, non-hemophilia bleeding disorders and a broader demographic (females, children, and infants) are being incorporated into study populations. Ongoing clinical trials broadly address three themes: (1) indication expansion for licensed therapeutics in previously uninvestigated patient subgroups or clinical scenarios, (2) evaluation of efficacy and safety among other bleeding disorders such as von Willebrand disease, platelet function defects, and rare clotting factor deficiencies, and (3) longitudinal assessment of approved treatments particularly with regard to longer-term efficacy outcomes such as musculoskeletal health and treatment-specific safety outcomes including thrombotic risk and liver health. With these new prophylaxis modalities, providers must have a nuanced understanding of each therapy's mechanism of action, advantages, side effect profile, therapeutic limitations, and impact on hemostasis and laboratory monitoring. Treatment is no longer “one size fits all.” Rather, management is tailored to individual needs and preferences. Here, we review active investigational trials and highlight promising approaches in preclinical development, expanding the innovative, complex landscape of inherited bleeding disorders therapeutics.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"12 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143084102","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}