Blood最新文献

{"title":"Itacitinib for prevention of graft-versus-host disease and cytokine release syndrome in haploidentical transplantation.","authors":"Ramzi Abboud, Mark A Schroeder, Michael P Rettig, Reyka G Jayasinghe, Feng Gao, Jeremy Eisele, Leah Gehrs, Julie Ritchey, Jaebok Choi, Camille N Abboud, Iskra Pusic, Meagan Jacoby, Peter Westervelt, Matthew Christopher, Amanda Cashen, Armin Ghobadi, Keith Stockerl-Goldstein, Geoffrey L Uy, John F DiPersio","doi":"10.1182/blood.2024026497","DOIUrl":"10.1182/blood.2024026497","url":null,"abstract":"<p><strong>Abstract: </strong>Haploidentical hematopoietic cell transplantation (haplo-HCT) is an increasingly used treatment for hematologic malignancies. Although posttransplant cyclophosphamide (PtCy) has improved graft-versus-host disease (GVHD) prophylaxis in haplo-HCT, patients continue to experience life-threatening complications. Interferon gamma and interleukin-6 are central in the pathophysiology of GVHD and cytokine release syndrome (CRS), and both cytokines signal through Janus kinase 1 (JAK-1). We tested the effect of adding the JAK-1 selective inhibitor, itacitinib, to PtCy-haplo-HCT to mitigate these complications and improve overall survival (OS). This open-label, single-arm study evaluated the safety and efficacy of itacitinib combined with standard GVHD prophylaxis after haplo-HCT. A total of 42 patients were treated with itacitinib 200 mg daily from day -3 through +100 or +180, followed by a taper. Itacitinib resulted in low CRS grades, all patients had grade 0 (22%) or grade 1 (78%) CRS and there were no cases of grade 2 to 5 CRS. There were no cases of primary graft failure. No patients developed grade 3 to 4 acute GVHD (aGVHD) through day +180. The cumulative incidence of grade 2 aGVHD at day +100 was 21.9%. The 1-year cumulative incidence of moderate or severe chronic GVHD was 5%. The cumulative incidence of relapse at 2 years was 14%. OS at 1 year was 80%. The cumulative incidence of nonrelapse mortality (NRM) at day 180 was 8%. Itacitinib, when added to standard GVHD prophylaxis, was well tolerated and resulted in low rates of CRS, acute and chronic GVHD, and NRM, and encouraging rates of GVHD-free relapse-free survival and OS after haplo-HCT. This trial was registered at www.ClinicalTrials.gov as #NCT03755414.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1382-1394"},"PeriodicalIF":21.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692556","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":"Use of machine learning techniques to predict poor survival after hematopoietic cell transplantation for myelofibrosis.","authors":"Juan Carlos Hernandez-Boluda, Adrian Mosquera Orgueira, Luuk Gras, Linda Koster, Joe Tuffnell, Nicolaus Kröger, Massimiliano Gambella, Thomas Schroeder, Marie Robin, Katja Sockel, Jakob R Passweg, Igor Wolfgang Blau, Ibrahim Yakoub-Agha, Ruben Van Dijck, Matthias Stelljes, Henrik Sengeloev, Jan Vydra, Uwe Platzbecker, Moniek Dewitte, Frédéric Baron, Kristina Carlson, Javier Alberto Rojas Martínez, Carlos Pérez Míguez, Davide Crucitti, Kavita Raj, Joanna Drozd-Sokolowska, Giorgia Battipaglia, Nicola Polverelli, Tomasz Czerw, Donal P McLornan","doi":"10.1182/blood.2024027287","DOIUrl":"https://doi.org/10.1182/blood.2024027287","url":null,"abstract":"<p><p>With the incorporation of effective therapies for myelofibrosis (MF), accurately predicting outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) is crucial for determining the optimal timing for this procedure. Using data from 5,183 MF patients who underwent first allo-HCT between 2005 and 2020 at EBMT centers, we examined different machine learning (ML) models to predict overall survival (OS) after transplant. The cohort was divided into a training set (75%) and a test set (25%) for model validation. A Random Survival Forests (RSF) model was developed based on 10 variables: patient age, comorbidity index, performance status, blood blasts, hemoglobin, leukocytes, platelets, donor type, conditioning intensity, and graft-versus-host disease prophylaxis. Its performance was compared with a four-level Cox regression-based score and other ML-based models derived from the same dataset, and with the CIBMTR score. The RSF outperformed all comparators, achieving better concordance indices across both primary and post-essential thrombocythemia/polycythemia vera MF subgroups. The robustness and generalizability of the RSF model was confirmed by Akaike's Information Criterion and time-dependent Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) metrics in both sets. While all models were prognostic for non-relapse mortality, the RSF provided better curve separation, effectively identifying a high-risk group comprising 25% of patients. In conclusion, ML enhances risk stratification in MF patients undergoing allo-HCT, paving the way for personalized medicine. A web application (https://gemfin.click/ebmt) based on the RSF model offers a practical tool to identify patients at high risk for poor transplantation outcomes, supporting informed treatment decisions and advancing individualized care.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717944","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 an AML-sustaining metabolic node.","authors":"Sarada Achyutuni, Jian Xu","doi":"10.1182/blood.2024027768","DOIUrl":"https://doi.org/10.1182/blood.2024027768","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 13","pages":"1341-1343"},"PeriodicalIF":21.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717960","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 WDR5/ATAD2 signaling by the CK2/IKAROS axis demonstrates therapeutic efficacy in T-ALL.","authors":"Qi Han, Yan Gu, Huimin Xiang, Linyao Zhang, Yan Wang, Chan Yang, Jun Li, Chelsea Steiner, Rosa Lapalombella, Jennifer A Woyach, Yiping Yang, Sinisa Dovat, Chunhua Song, Zheng Ge","doi":"10.1182/blood.2024024130","DOIUrl":"10.1182/blood.2024024130","url":null,"abstract":"<p><strong>Abstract: </strong>T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a poor prognosis and limited options for targeted therapies. Identifying new molecular targets to develop novel therapeutic strategies is the pressing immediate issue in T-ALL. Here, we observed high expression of WD repeat-containing protein 5 (WDR5) in T-ALL. With in vitro and in vivo models, we demonstrated the oncogenic role of WDR5 in T-ALL by activating cell cycle signaling through its new downstream effector, ATPase family AAA domain-containing 2 (ATAD2). Moreover, the function of a zinc finger transcription factor of the Kruppel family (IKAROS) is often impaired by genetic alteration and casein kinase II (CK2) which is overexpressed in T-ALL. We found that IKAROS directly regulates WDR5 transcription; CK2 inhibitor, CX-4945, strongly suppresses WDR5 expression by restoring IKAROS function. Last, combining CX-4945 with WDR5 inhibitor demonstrates synergistic efficacy in the patient-derived xenograft mouse models. In conclusion, our results demonstrated that WDR5/ATAD2 is a new oncogenic signaling pathway in T-ALL, and simultaneous targeting of WRD5 and CK2/IKAROS has synergistic antileukemic efficacy and represents a promising potential strategy for T-ALL therapy.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1407-1421"},"PeriodicalIF":21.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944653","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":"PGE2 inhibition to prevent AML escape from NK cells.","authors":"Federico Simonetta","doi":"10.1182/blood.2024027931","DOIUrl":"https://doi.org/10.1182/blood.2024027931","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 13","pages":"1338-1339"},"PeriodicalIF":21.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717955","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":"Two is better than one: dual targeting of WDR5 in T-ALL.","authors":"Alexander A Wurm, Denis M Schewe","doi":"10.1182/blood.2024027633","DOIUrl":"https://doi.org/10.1182/blood.2024027633","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 13","pages":"1339-1341"},"PeriodicalIF":21.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717965","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":"Warthin-Finkeldey cells seen in a setting other than measles: chronic lymphocytic leukemia/small lymphocytic lymphoma.","authors":"Tanner J Bakhshi, Sergio Pina-Oviedo","doi":"10.1182/blood.2024028017","DOIUrl":"https://doi.org/10.1182/blood.2024028017","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 13","pages":"1437"},"PeriodicalIF":21.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717968","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":"Atypical chronic myeloid leukemia: from cytology to molecular characterization.","authors":"Aida Calo-Pérez, Raquel Martínez-Fernández","doi":"10.1182/blood.2024027505","DOIUrl":"https://doi.org/10.1182/blood.2024027505","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 13","pages":"1438"},"PeriodicalIF":21.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717953","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":"How I diagnose and treat acute infection-associated purpura fulminans.","authors":"Pavan K Bendapudi, Julie-Aurore Losman","doi":"10.1182/blood.2024025078","DOIUrl":"10.1182/blood.2024025078","url":null,"abstract":"<p><strong>Abstract: </strong>Purpura fulminans (PF) is a rare but devastating complication of sepsis characterized by a highly thrombotic subtype of disseminated intravascular coagulation (DIC). A medical emergency, PF often requires the involvement of consultant hematologists to assist with diagnosis and management of patients who are in a highly dynamic and deteriorating clinical situation. Patients who survive past the first 24 to 72 hours often die from complications of unchecked thrombosis rather than shock, and survivors are usually left with severe scarring and tissue loss. Despite these challenging features, PF is a pathophysiologically distinct, homogeneous, and highly predictable form of sepsis-associated DIC for which poor outcomes are not a foregone conclusion. The fundamental pathologic lesion in PF is a failure of the anticoagulant protein C pathway, which leads to uncontrolled microvascular clotting and inadequate protein C-mediated cytoprotective effects, which are vital for survival in sepsis. Herein, we review the clinical features and diagnosis of PF. Drawing from existing clinical literature and recent advances in our understanding of the pathophysiology of PF, we describe rationally designed treatment approaches for this disorder, including repletion of natural circulating anticoagulants, use of therapeutic anticoagulation, and ways to optimize transfusion support, and we outline specific interventions that we would recommend avoiding.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1358-1368"},"PeriodicalIF":21.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944639","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":"Sickle cell trait does not cause \"sickle cell crisis\" leading to exertion-related death: a systematic review.","authors":"Lachelle D Weeks, Allecia M Wilson, Rakhi P Naik, Yvonne Efebera, M Hassan Murad, Anjlee Mahajan, Patrick T McGann, Madeleine Verhovsek, Angela C Weyand, Ahmar U Zaidi, Michael R DeBaun, Chancellor Donald, Roger A Mitchell","doi":"10.1182/blood.2024026899","DOIUrl":"10.1182/blood.2024026899","url":null,"abstract":"<p><strong>Abstract: </strong>Globally, an estimated 300 million individuals have sickle cell trait (SCT), the carrier state for sickle cell disease (SCD). Although SCD is associated with increased morbidity and shortened life span, SCT has a life span comparable with that of the general population. However, \"sickle cell crisis\" has been used as a cause of death for decedents with SCT in reports of exertion-related death in athletes, military personnel, and individuals in police custody. To appraise this practice, the American Society of Hematology convened an expert panel of hematologists and forensic pathologists to conduct a systematic review of the literature relating to the occurrence of sickle cell pain crises and exertion-related mortality in people with SCT. Multiple bibliographic databases were searched with controlled vocabulary and keywords related to \"sickle cell trait,\" \"vaso-occlusive pain,\" and \"death,\" yielding 18 of 1474 citations. Independent pairs of reviewers selected studies and extracted data. We found no studies comparing uncomplicated acute pain crises in individuals with SCT and SCD. Additionally, no study was identified to support the occurrence of acute vaso-occlusive pain crises in individuals with SCT. Furthermore, this systematic review did not identify any evidence to support an association between SCT and sudden unexplained death in the absence of exertion-related rhabdomyolysis. We conclude that there are no data to support the diagnosis of acute vaso-occlusive sickle cell crisis as a cause of death in SCT, nor does the available evidence support the use of SCT as a cause of exertion-related death without rhabdomyolysis.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1345-1352"},"PeriodicalIF":21.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063656","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}