Pub Date : 2024-11-14DOI: 10.1182/blood.2024026571
Rick Kapur, John W Semple
{"title":"Let's YAP about ITP.","authors":"Rick Kapur, John W Semple","doi":"10.1182/blood.2024026571","DOIUrl":"https://doi.org/10.1182/blood.2024026571","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"144 20","pages":"2072-2073"},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614362","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}
Pub Date : 2024-11-14DOI: 10.1182/blood.2024024248
Alexander E Perl
Combining FLT3 inhibitors with intensive chemotherapy and transplant has substantially improved AML outcomes, prompting a recent re-evaluation of FLT3-ITD's historically negative prognostic effect. Treatment approaches may soon undergo major changes as emerging data suggest maximal intensity does not benefit all patients and MRD potentially can guide several treatment choices. Finally, recent data also suggest FLT3 inhibitors could transform outcomes in patients unsuitable for intensive therapy. If confirmed, this has important implications for fit patients and could revolutionize the treatment paradigm.
{"title":"Approaching a therapeutic inflection point for FLT3-mutated AML.","authors":"Alexander E Perl","doi":"10.1182/blood.2024024248","DOIUrl":"https://doi.org/10.1182/blood.2024024248","url":null,"abstract":"<p><p>Combining FLT3 inhibitors with intensive chemotherapy and transplant has substantially improved AML outcomes, prompting a recent re-evaluation of FLT3-ITD's historically negative prognostic effect. Treatment approaches may soon undergo major changes as emerging data suggest maximal intensity does not benefit all patients and MRD potentially can guide several treatment choices. Finally, recent data also suggest FLT3 inhibitors could transform outcomes in patients unsuitable for intensive therapy. If confirmed, this has important implications for fit patients and could revolutionize the treatment paradigm.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614324","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}
Pub Date : 2024-11-14DOI: 10.1182/blood.2024025699
Gloria Iacoboni, Franck Morschhauser
Follicular lymphoma (FL) usually requires multiple lines of therapy and disease control remains largely insufficient with conventional chemoimmunotherapy. Several T-cell redirecting strategies recently approved in the relapsed/refractory setting have the potential to improve outcomes and change the treatment algorithm in FL. This review focuses on the role of chimeric antigen receptor T-cells and bispecific antibodies in FL, paying special attention to sequencing approaches and future directions.
{"title":"Building the Future Management of Follicular Lymphoma with T-Cell-Redirecting Strategies.","authors":"Gloria Iacoboni, Franck Morschhauser","doi":"10.1182/blood.2024025699","DOIUrl":"https://doi.org/10.1182/blood.2024025699","url":null,"abstract":"<p><p>Follicular lymphoma (FL) usually requires multiple lines of therapy and disease control remains largely insufficient with conventional chemoimmunotherapy. Several T-cell redirecting strategies recently approved in the relapsed/refractory setting have the potential to improve outcomes and change the treatment algorithm in FL. This review focuses on the role of chimeric antigen receptor T-cells and bispecific antibodies in FL, paying special attention to sequencing approaches and future directions.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614242","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}
Pub Date : 2024-11-14DOI: 10.1182/blood.2024026120
Tomomi Toubai
{"title":"Ruxolitinib REACHes FOR children with GVHD.","authors":"Tomomi Toubai","doi":"10.1182/blood.2024026120","DOIUrl":"https://doi.org/10.1182/blood.2024026120","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"144 20","pages":"2069-2070"},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614470","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}
Pub Date : 2024-11-14DOI: 10.1182/blood.2024025627
Alexandre Guy, Pierre-Emmanuel Morange, Chloé James
Arterial and venous thromboses are the most significant complications in patients with myeloproliferative neoplasms (MPN), with the primary treatment goal being thrombotic risk reduction. In MPN with no history of thrombosis, primary prevention mainly involves the use of aspirin and cytoreduction is added in high-risk patients. However, thrombotic complications can unveil an MPN in approximately 20% of cases, necessitating the initiation of both antithrombotic therapy for the thrombosis and cytoreductive treatment for the MPN. The duration of anticoagulant therapy following an initial venous thromboembolic event (VTE) is subject to discussion. Furthermore, the occurrence of a thrombotic complication in patients with a known diagnosis of MPN prompts a reconsideration of both antithrombotic and hematological management. This review employs case-based discussions to explore the management of thrombotic complications in MPN patients. It addresses the nature and duration of antithrombotic treatments, as well as the approach to cytoreduction. Special attention is given to the place of direct oral anticoagulants and to the management of MPN patients with splanchnic vein thrombosis, which is disproportionately common in this group.
{"title":"How I approach the treatment of thrombotic complications in patients with myeloproliferative neoplasms.","authors":"Alexandre Guy, Pierre-Emmanuel Morange, Chloé James","doi":"10.1182/blood.2024025627","DOIUrl":"https://doi.org/10.1182/blood.2024025627","url":null,"abstract":"<p><p>Arterial and venous thromboses are the most significant complications in patients with myeloproliferative neoplasms (MPN), with the primary treatment goal being thrombotic risk reduction. In MPN with no history of thrombosis, primary prevention mainly involves the use of aspirin and cytoreduction is added in high-risk patients. However, thrombotic complications can unveil an MPN in approximately 20% of cases, necessitating the initiation of both antithrombotic therapy for the thrombosis and cytoreductive treatment for the MPN. The duration of anticoagulant therapy following an initial venous thromboembolic event (VTE) is subject to discussion. Furthermore, the occurrence of a thrombotic complication in patients with a known diagnosis of MPN prompts a reconsideration of both antithrombotic and hematological management. This review employs case-based discussions to explore the management of thrombotic complications in MPN patients. It addresses the nature and duration of antithrombotic treatments, as well as the approach to cytoreduction. Special attention is given to the place of direct oral anticoagulants and to the management of MPN patients with splanchnic vein thrombosis, which is disproportionately common in this group.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614283","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}
Pub Date : 2024-11-14DOI: 10.1182/blood.2024026349
Arielle L Langer
{"title":"Oxidative hemolysis due to phenazopyridine in the absence of G6PD deficiency.","authors":"Arielle L Langer","doi":"10.1182/blood.2024026349","DOIUrl":"https://doi.org/10.1182/blood.2024026349","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"144 20","pages":"2155"},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614367","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}
Pub Date : 2024-11-14DOI: 10.1182/blood.2024025702
Yasmin Abaza, Amy E DeZern
Anemia is the most prevalent cytopenia in lower-risk myelodysplastic neoplasms (LR-MDS). There is a paucity of drugs for red blood cell transfusion dependence (RBC-TD) and erythropoiesis-stimulating agents (ESAs) are the mainstay of therapy in many centers. Imetelstat, an oligonucleotide telomerase inhibitor, was recently approved for RBC-TD LR-MDS adults who are ineligible or failed prior ESA therapy. While not yet approved worldwide, here, we spotlight the current data for imetelstat and where it may fit in the therapeutic landscape of LR-MDS.
{"title":"Imetelstat: A new addition to the Therapeutic Landscape of Lower-Risk MDS.","authors":"Yasmin Abaza, Amy E DeZern","doi":"10.1182/blood.2024025702","DOIUrl":"https://doi.org/10.1182/blood.2024025702","url":null,"abstract":"<p><p>Anemia is the most prevalent cytopenia in lower-risk myelodysplastic neoplasms (LR-MDS). There is a paucity of drugs for red blood cell transfusion dependence (RBC-TD) and erythropoiesis-stimulating agents (ESAs) are the mainstay of therapy in many centers. Imetelstat, an oligonucleotide telomerase inhibitor, was recently approved for RBC-TD LR-MDS adults who are ineligible or failed prior ESA therapy. While not yet approved worldwide, here, we spotlight the current data for imetelstat and where it may fit in the therapeutic landscape of LR-MDS.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614296","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}
Pub Date : 2024-11-14DOI: 10.1182/blood.2024026109
Angelo D'Alessandro, Gregory R Keele, Ariel M Hay, Travis Nemkov, Eric J Earley, Daniel Stephenson, Matthew Vincent, Xutao Deng, Mars Stone, Monika Dzieciatkowska, Kirk C Hansen, Steven H Kleinman, Steven L Spitalnik, Nareg H Roubinian, Philip J Norris, Michael P Busch, Grier P Page, Brent Stockwell, Gary A Churchill, James C Zimring
Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. However, the genetic underpinnings of RBC metabolic heterogeneity and extravascular hemolysis at population scale are incompletely understood. Based on the breeding of 8 founder strains with extreme genetic diversity, the Jackson laboratory diversity outbred population can capture the impact of genetic heterogeneity in like fashion to population-based studies. RBCs from 350 outbred mice, either fresh or stored for 7 days, were tested for post-transfusion recovery, as well as metabolomics and lipidomics analyses. Metabolite and lipid Quantitative Trait Loci (QTL) mapped >400 gene-metabolite associations, which we collated into an online interactive portal. Relevant to RBC storage, we identified a QTL hotspot on chromosome 1, mapping on the region coding for the ferrireductase Steap3, a transcriptional target to p53. Steap3 regulated post-transfusion recovery, contributing to a ferroptosis-like process of lipid peroxidation, as validated via genetic manipulation in mice. Translational validation of murine findings in humans, STEAP3 polymorphisms were associated with RBC iron content, lipid peroxidation and in vitro hemolysis in 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. QTL analyses in humans identified a network of gene products (FADS1/2, EPHX2, LPCAT3, SLC22A16, G6PD, ELOVL, PLA2G6) associated with lower levels of oxylipins. These polymorphisms were prevalent in donors of African descent and were linked to allele frequency of hemolysis-linked polymorphisms for Steap3 or p53. These genetic variants were also associated with lower hemoglobin increments in thousands of single-unit transfusion recipients from the vein-to-vein database.
{"title":"Ferroptosis regulates hemolysis in stored murine and human red blood cells.","authors":"Angelo D'Alessandro, Gregory R Keele, Ariel M Hay, Travis Nemkov, Eric J Earley, Daniel Stephenson, Matthew Vincent, Xutao Deng, Mars Stone, Monika Dzieciatkowska, Kirk C Hansen, Steven H Kleinman, Steven L Spitalnik, Nareg H Roubinian, Philip J Norris, Michael P Busch, Grier P Page, Brent Stockwell, Gary A Churchill, James C Zimring","doi":"10.1182/blood.2024026109","DOIUrl":"10.1182/blood.2024026109","url":null,"abstract":"<p><p>Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. However, the genetic underpinnings of RBC metabolic heterogeneity and extravascular hemolysis at population scale are incompletely understood. Based on the breeding of 8 founder strains with extreme genetic diversity, the Jackson laboratory diversity outbred population can capture the impact of genetic heterogeneity in like fashion to population-based studies. RBCs from 350 outbred mice, either fresh or stored for 7 days, were tested for post-transfusion recovery, as well as metabolomics and lipidomics analyses. Metabolite and lipid Quantitative Trait Loci (QTL) mapped >400 gene-metabolite associations, which we collated into an online interactive portal. Relevant to RBC storage, we identified a QTL hotspot on chromosome 1, mapping on the region coding for the ferrireductase Steap3, a transcriptional target to p53. Steap3 regulated post-transfusion recovery, contributing to a ferroptosis-like process of lipid peroxidation, as validated via genetic manipulation in mice. Translational validation of murine findings in humans, STEAP3 polymorphisms were associated with RBC iron content, lipid peroxidation and in vitro hemolysis in 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. QTL analyses in humans identified a network of gene products (FADS1/2, EPHX2, LPCAT3, SLC22A16, G6PD, ELOVL, PLA2G6) associated with lower levels of oxylipins. These polymorphisms were prevalent in donors of African descent and were linked to allele frequency of hemolysis-linked polymorphisms for Steap3 or p53. These genetic variants were also associated with lower hemoglobin increments in thousands of single-unit transfusion recipients from the vein-to-vein database.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614268","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}
Pub Date : 2024-11-14DOI: 10.1182/blood.2024026430
Madhav V Dhodapkar
{"title":"Location, location, location: EMD in MM.","authors":"Madhav V Dhodapkar","doi":"10.1182/blood.2024026430","DOIUrl":"https://doi.org/10.1182/blood.2024026430","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"144 20","pages":"2070-2071"},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614363","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}
Pub Date : 2024-11-01Epub Date: 2022-06-10DOI: 10.1177/11297298221103201
Isabella Santomauro, Daiana Campani, Valentina Tiozzo, Barbara Barletta, Lorenza Scotti, Michela Barisone, Alberto Dal Molin
Venous access devices are used in health care. To prevent occlusions the evidence confirmed the need for routine catheter flushing before and after infusion as well as at the end of use. To date, the efficacy of heparin has not been demonstrated. The aim of this study was to evaluate the effectiveness of the locking of central venous catheters with heparin versus normal saline in adults to prevent occlusion, catheter-related infections and thrombosis in adults. A literature search using Medline, Embase, Cochrane Library and Cinahl was performed to identify all meta-analyses addressing the effectiveness of heparin versus normal saline in locking central venous catheters in adults. Four reviewers independently selected publications assessed quality and extracted data. Parameter estimates regarding occlusion, catheter- related infections and thrombosis were pooled using an umbrella review. We identified 6356 references. Seven systematic reviews were included in the study. Most of the studies included in the systematic reviews were conducted in oncohaematology departments, intensive care and cardiac surgery units among patients with multiple diseases and chronicity. Most studies report a heparin concentration of 10 to 5000 IU/ml versus normal saline and other solutions. There was no evidence that heparin was more effective than normal saline in reducing complications such as occlusion, catheter-related infections and thrombosis. No statistically significant difference was found between heparin and normal saline in reducing catheter occlusion. Heparin is not superior compared to normal saline.
{"title":"Heparin versus normal saline locking for prevention of occlusion, catheter-related infections and thrombosis in central venous catheter in adults: Overview of systematic reviews.","authors":"Isabella Santomauro, Daiana Campani, Valentina Tiozzo, Barbara Barletta, Lorenza Scotti, Michela Barisone, Alberto Dal Molin","doi":"10.1177/11297298221103201","DOIUrl":"10.1177/11297298221103201","url":null,"abstract":"<p><p>Venous access devices are used in health care. To prevent occlusions the evidence confirmed the need for routine catheter flushing before and after infusion as well as at the end of use. To date, the efficacy of heparin has not been demonstrated. The aim of this study was to evaluate the effectiveness of the locking of central venous catheters with heparin versus normal saline in adults to prevent occlusion, catheter-related infections and thrombosis in adults. A literature search using Medline, Embase, Cochrane Library and Cinahl was performed to identify all meta-analyses addressing the effectiveness of heparin versus normal saline in locking central venous catheters in adults. Four reviewers independently selected publications assessed quality and extracted data. Parameter estimates regarding occlusion, catheter- related infections and thrombosis were pooled using an umbrella review. We identified 6356 references. Seven systematic reviews were included in the study. Most of the studies included in the systematic reviews were conducted in oncohaematology departments, intensive care and cardiac surgery units among patients with multiple diseases and chronicity. Most studies report a heparin concentration of 10 to 5000 IU/ml versus normal saline and other solutions. There was no evidence that heparin was more effective than normal saline in reducing complications such as occlusion, catheter-related infections and thrombosis. No statistically significant difference was found between heparin and normal saline in reducing catheter occlusion. Heparin is not superior compared to normal saline.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":"138 1","pages":"1741-1748"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74268436","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}