European Journal of Haematology最新文献

{"title":"Real-World Evidence on Prognostic Value of MRD in Multiple Myeloma Using Flow Cytometry","authors":"Ludmila Muronova,&nbsp;Ondrej Soucek,&nbsp;David Zihala,&nbsp;Tereza Sevcikova,&nbsp;Tereza Popkova,&nbsp;Hana Plonkova,&nbsp;Ondrej Venglar,&nbsp;Ludek Pour,&nbsp;Martin Stork,&nbsp;Lucie Rihova,&nbsp;Renata Bezdekova,&nbsp;Jiri Minarik,&nbsp;Vojtech Látal,&nbsp;Martin Novak,&nbsp;Alexandra Jungova,&nbsp;Tereza Dekojova,&nbsp;Jan Straub,&nbsp;Martin Spacek,&nbsp;Vladimira Rezacova,&nbsp;Vladimir Maisnar,&nbsp;Jakub Radocha,&nbsp;Roman Hajek,&nbsp;Tomas Jelinek","doi":"10.1111/ejh.14316","DOIUrl":"10.1111/ejh.14316","url":null,"abstract":"<p>Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression-free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real-world setting. In this retrospective multicenter study, we report outcomes of 331 newly diagnosed MM patients with MRD evaluation at Day+100 after autologous stem cell transplantation using flow cytometry with a median limit of detection of 0.001%. MRD negativity was reached in 47% of patients and was associated with significantly prolonged median PFS (49.2 months vs. 18.4 months; hazard ratios (HR) = 0.37; <i>p</i> &lt; 0.001) and OS (not reached vs. 74.9 months; HR = 0.50; <i>p</i> = 0.007). Achieving MRD negativity was associated with PFS improvements regardless of age, International Staging System (ISS) stage, lactate dedydrogenase (LDH) level, or cytogenetic risk. Importantly, MRD positive patients benefited from lenalidomide maintenance versus no maintenance (18-months PFS: 81% vs. 46%; HR = 0.24; <i>p</i> = 0.002) while in MRD negative patients such benefit was not observed (<i>p</i> = 0.747). The outcomes of our real-world study recapitulate results from clinical trials including meta-analyses and support the idea that MRD positive patients profit more from lenalidomide maintenance than MRD negative ones.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"155-163"},"PeriodicalIF":2.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14316","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Intensity Conditioning Prior Autologous Stem Cell Transplantation in Elderly DLBCL Patients","authors":"Tim Strüßmann,&nbsp;Philipp Hermes,&nbsp;Gabriele Ihorst,&nbsp;Jürgen Finke,&nbsp;Jesús Duque-Afonso,&nbsp;Monika Engelhardt,&nbsp;Justus Duyster,&nbsp;Reinhard Marks","doi":"10.1111/ejh.14320","DOIUrl":"10.1111/ejh.14320","url":null,"abstract":"<p>High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is widely used in patients with diffuse large B-cell lymphoma. HDCT/ASCT is associated with increased morbidity in elderly/unfit patients. We retrospectively evaluated the use of reduced intensity conditioning in DLBCL patients. Our study included 146 patients aged 60 years and older treated at our institution between 2005 and 2019; 86 patients received standard intensity conditioning (SI group) with BEAM or TEAM (BCNU or thiotepa, etoposide, cytarabine, melphalan). Sixty patients received reduced intensity high-dose conditioning (RI group) with BM (BCNU, melphalan, 43.3%), TM (thiotepa, melphalan, 16.7%), BCNU or busulfan thiotepa (38.4%), or bendamustine melphalan (1.7%). Median follow-up was 62.4 months. We observed comparable toxicities in the SI and RI groups. The cumulative incidence of relapse at 3 years was higher in the RI group (30.8% vs. 23.4%, <i>p</i> = 0.034). There was no difference in nonrelapse mortality (NRM). In univariate analyses, SI vs. RI conditioning resulted in superior progression-free survival (PFS) (HR 1.80 CI 1.11–2.92, <i>p</i> = 0.017) but not in superior overall survival (OS) (HR 1.48 CI 0.86–2.56, <i>p</i> = 0.152). On multivariate analysis, we observed no difference in PFS (HR 0.74 CI 0.40–1.38, <i>p</i> = 0.345) and a trend toward better OS with RI conditioning (HR 0.45 CI 0.22–0.94, <i>p</i> = 0.032). Age 60–69 versus ≥ 70 years and remission prior to ASCT were the only factors predicting better PFS. Factors associated with better OS were RI conditioning, age 60–69 versus ≥ 70 years, ECOG 0 versus ≥ 1 performance status, bulky disease, and prior lines 1 versus ≥ 2. In conclusion, RI conditioning prior to ASCT may be feasible in elderly patients and led to a comparable outcome when corrected for several significant confounders.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"139-146"},"PeriodicalIF":2.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging Multi-Omics Approaches and Advanced Technologies to Unravel the Molecular Complexities, Modifiers, and Precision Medicine Strategies for Hemoglobin H Disease","authors":"Akshata Pahelkar,&nbsp;Deep Sharma,&nbsp;Payaam Vohra,&nbsp;Sayli Sawant","doi":"10.1111/ejh.14319","DOIUrl":"10.1111/ejh.14319","url":null,"abstract":"<p>Hemoglobin H (HbH) disease, a form of alpha-thalassemia, poses significant clinical challenges due to its complex molecular underpinnings. It is characterized by reduced synthesis of the alpha-globin chain. The integration of multi-omics and precision medicine holds immense potential to comprehensively understand and capture interactions at the molecular and genetic levels. This review integrates current multi-omics approaches and advanced technologies in HbH research. Furthermore, it delves into detailed pathophysiology and possible therapeutics in the upcoming future. We explore the role of genomics, transcriptomics, proteomics, and metabolomics studies, alongside bioinformatics tools and gene-editing technologies like CRISPR/Cas9, to identify genetic modifiers, decipher molecular pathways, and discover therapeutic targets. Recent advancements are unveiling novel genetic and epigenetic modifiers impacting HbH disease severity, paving the way for personalized precision medicine interventions. The significance of multi-omics research in unraveling the complexities of rare diseases like HbH is underscored, highlighting its potential to revolutionize clinical practice through precision medicine approaches. This paradigm shift can pave the way for a deeper understanding of HbH complexities and improved disease management.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 6","pages":"738-744"},"PeriodicalIF":2.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overall Survival and Treatment Patterns Among Patients With Warm Autoimmune Hemolytic Anemia in Sweden: A Nationwide Population-based Study","authors":"Honar Cherif,&nbsp;Qian Cai,&nbsp;Concetta Crivera,&nbsp;Ann Leon,&nbsp;Iffat Rahman,&nbsp;Amy Leval,&nbsp;Wim Noel,&nbsp;Christian Kjellander","doi":"10.1111/ejh.14311","DOIUrl":"10.1111/ejh.14311","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Warm autoimmune hemolytic anemia (wAIHA) is a rare autoantibody-mediated disorder, and first-line treatment primarily relies on corticosteroids. This study assessed overall survival (OS) and treatment patterns of wAIHA in Sweden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adults with ≥ 1 primary diagnosis code for wAIHA (or AIHA plus oral corticosteroids (OCS)/immunosuppressants as sensitivity analyses) between 2011 and 2022 were identified from five Swedish national registers and linked through each patient's unique identity number. Kaplan–Meier curves with log-rank tests and Cox regressions were performed to assess OS for patients with primary versus secondary wAIHA and patients with wAIHA and long-term versus short-term (≥ 3 vs. &lt; 3 months) OCS users.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The main analysis included 292 patients; 1791 patients were included in the sensitivity analysis. At a median 3.7-year follow-up, a median OS in primary wAIHA was not reached versus 6.0 years for secondary wAIHA (log-rank test: <i>p</i> = 0.003). Subgroup analyses showed no significant difference in risk of death between long-term and short-term OCS users; however, in the sensitivity analysis, long-term OCS users showed significantly higher risk of death (adjusted hazard ratio: 1.45; 95% confidence interval: 1.180, 1.781; <i>p</i> &lt; 0.001) versus short-term OCS users.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Secondary wAIHA or long-term OCS use was associated with lower OS, underscoring the disease burden and unmet need for efficacious wAIHA treatments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"129-138"},"PeriodicalIF":2.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infusion Reactions With Alternative Therapies During the National Shortage of Iron Dextran","authors":"Brigid Jacob,&nbsp;Maria Jamil,&nbsp;Shahm Raslan,&nbsp;Kylie Springer,&nbsp;Zeinab Nasser,&nbsp;Philip Kuriakose","doi":"10.1111/ejh.14322","DOIUrl":"10.1111/ejh.14322","url":null,"abstract":"<div>\u0000 \u0000 <p>Prior to the national shortage of iron dextran in early 2023, it was the most commonly administered intravenous iron infusion at our institution. After the shortage impacted the health system, alternatives such as iron sucrose and sodium ferric gluconate/sucrose were required that utilized lower doses given at more frequent patient visits. Coinciding with their more prevalent use, an increase in iron infusion reactions was observed. Our study analyzed 880 patients who received iron infusions in three Henry Ford Hospital clinics in metropolitan Detroit, Michigan, from July 2022–June 2023. The 74 reactions that occurred were most commonly associated with iron sucrose at the 500 mg dose (41/74, 55.41%, <i>p</i> &lt; 0.0001). Most reactions observed across all iron formulations and doses were mild, with 83.7% being Grade 0 or 1 as defined by the United States Drug Allergy Registry (USDAR) grading scale for immediate reactions. Patients who experienced an infusion reaction were less likely to complete their infusion plans (OR 0.004 for iron dextran, OR 0.128 for iron sucrose, <i>p</i> &lt; 0.0001), with infusions most commonly being completely discontinued thereafter, with a minority pursuing alternative options. More patients with lower number of doses scheduled for iron dextran completed their infusion schedules than those with more doses, but the opposite was seen for iron sucrose. We assessed the impact of the national shortage of iron dextran examining infusion reactions with various iron infusions and doses.</p>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"147-154"},"PeriodicalIF":2.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Gut Microbiota and Inflammatory Cytokines on Immune Thrombocytopenia","authors":"Ji-Gan Wang,&nbsp;Hui-Hong Dou,&nbsp;Qiong-You Liang","doi":"10.1111/ejh.14310","DOIUrl":"10.1111/ejh.14310","url":null,"abstract":"<div>\u0000 \u0000 <p>Immune thrombocytopenic purpura (ITP) is an autoimmune disorder, and recent research suggests that gut microbiota and inflammatory cytokines may play a significant role in its pathogenesis. However, the specific effects of these factors on ITP and their relationships remain unclear. We conducted a two-step, two-sample Mendelian randomization study using an inverse variance-weighted approach to investigate the causal role of the gut microbiota in ITP and the mediating effect of inflammatory cytokines on their association. The results showed that among the 473 gut microbiota species, 11 were positively associated and 12 were negatively associated with the risk of ITP. Among the 91 screened inflammatory cytokines, five (CXCL10, CXCL5, IL-12RA, TRAIL, and VEGF-A) were found to have a causal relationship with ITP. Mediation analysis revealed that the gut microbiota UBA1066 promoted the occurrence of ITP through CXCL10 mediation, with a mediation effect of 0.118932 (95% CI: 0.049471–0.188393) accounting for 9.95% of the total effect. Gut microbiota <i>Treponema</i> promoted ITP through VEGF-A mediation, with a mediation effect of 0.045873 (95% CI: 0.01456–0.07718) accounting for 4.28% of the total effect. Gut microbiota <i>Haloplasma</i> promoted the occurrence of ITP via CXCL5. The mediating effect of CXCL5 was 0.038409 (95% CI = 0.00107718–0.07575082), with a mediating ratio of 16.79%. This study revealed a causal relationship between gut microbiota composition and ITP risk, highlighting three inflammatory cytokines as potential causal mediators of this relationship. These findings provide potential targets and biomarkers for the prevention and treatment of ITP with significant clinical implications.</p>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"120-128"},"PeriodicalIF":2.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Efficacy of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients","authors":"Danilo De Novellis,&nbsp;Daniele Derudas,&nbsp;Donatella Vincelli,&nbsp;Raffaele Fontana,&nbsp;Roberta Della Pepa,&nbsp;Salvatore Palmieri,&nbsp;Fabrizio Accardi,&nbsp;Francesco Rotondo,&nbsp;Emanuela Morelli,&nbsp;Emilia Gigliotta,&nbsp;Daniela Roccotelli,&nbsp;Luana Marano,&nbsp;Maria Lucia Barone,&nbsp;Giusy Cetani,&nbsp;Daniela Esposito,&nbsp;Antonio Lazzaro,&nbsp;Giuseppe Delle Cave,&nbsp;Bianca Serio,&nbsp;Denise Morini,&nbsp;Marika Porrazzo,&nbsp;Eleonora Urciuoli,&nbsp;Chiara Masucci,&nbsp;Fulvia Fanelli,&nbsp;Michela Rizzo,&nbsp;Manuela Arcamone,&nbsp;Fabio Trastulli,&nbsp;Stefano Rocco,&nbsp;Aldo Leone,&nbsp;Rosario Bianco,&nbsp;Flavia Salvatore,&nbsp;Aurora Idato,&nbsp;Maria Sicari,&nbsp;Patrizia Tosi,&nbsp;Maria Gabriella Rascato,&nbsp;Maria Di Perna,&nbsp;Antonietta Pia Falcone,&nbsp;Lucia Morello,&nbsp;Melania Carlisi,&nbsp;Gino Svanera,&nbsp;Mario Annunziata,&nbsp;Ferdinando Frigeri,&nbsp;Catello Califano,&nbsp;Angelo Michele Carella,&nbsp;Gianpaolo Marcacci,&nbsp;Fabrizio Pane,&nbsp;Antonio Maria Risitano,&nbsp;Valentina Giudice,&nbsp;Ciro Botta,&nbsp;Carmine Selleri","doi":"10.1111/ejh.14314","DOIUrl":"10.1111/ejh.14314","url":null,"abstract":"<p>Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1-year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (<i>N</i> = 69) treated with Isa-Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1-year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa-Kd as an effective treatment option for RRMM with a manageable safety profile even in real-life settings.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"105-114"},"PeriodicalIF":2.3,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Human-Level and Machine Learning Model Performance in White Blood Cell Morphology Assessment","authors":"Patrick Lawrence,&nbsp;Christina Brown","doi":"10.1111/ejh.14318","DOIUrl":"10.1111/ejh.14318","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>There is an increasing research focus on the role of machine learning in the haematology laboratory, particularly in blood cell morphologic assessment. Human-level performance is an important baseline and goal for machine learning. This study aims to assess the interobserver variability and human-level performance in blood cell morphologic assessment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A dataset of 1000 single white blood cell images were independently labelled by 10 doctors and morphology scientists. Interobserver variability was calculated using Fleiss' kappa. Observers' labels were then separated into consensus labels used to determine ground truth, and performance labels used to assess observer performance. A machine learning model was trained and assessed using the same cell images. Explainability images (XRAI and IG) were generated for each of the test images.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Fleiss kappa for all 10 observers was 0.608, indicating substantial agreement between observers. The accuracy of human observers was 95%, with sensitivity 72% and specificity 97%. The accuracy of the machine learning model was 95%, with sensitivity 71% and specificity 97%. The model shared similar performance across labels when compared to humans. Explainability metrics demonstrated that the machine learning model was able to differentiate between the cytoplasm and nucleus of the cells, and used these features to perform predictions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The substantial, though not perfect, agreement between human observers highlights the inherent subjectivity in white blood cell morphologic assessment. A machine learning model performed similarly to human observers in single white blood cell identification. Further research is needed to compare human-level and machine learning performance in ways that more closely reflect the typical process of morphologic assessment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"115-119"},"PeriodicalIF":2.3,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ICAM1 to Ameliorate Vaso-Occlusion and Inflammation in Sickle Cell Disease","authors":"Parul Gupta,&nbsp;Ravindra Kumar","doi":"10.1111/ejh.14313","DOIUrl":"10.1111/ejh.14313","url":null,"abstract":"<p>Sickle cell disease (SCD) is a hereditary disorder characterized by vaso-occlusion, inflammation, and tissue damage. Intercellular adhesion molecule 1 (ICAM-1) plays a crucial role in the pathophysiology of SCD by promoting the adhesion of sickle cells to the endothelium, contributing to vaso-occlusion and tissue damage. The ICAM-1 gene encodes a glycoprotein that interacts with lymphocyte function–associated antigen 1 (LFA-1) and macrophage 1-antigen (Mac-1) receptors, perpetuating inflammation, and oxidative stress. The NF-κB signaling pathway regulates ICAM-1 expression, which is elevated in patients with SCD, leading to increased endothelial cell activation and damage. Targeting ICAM-1 and its interactions with sickle cells and the endothelium has emerged as a potential therapeutic strategy for managing SCD. This review highlights the complex interplay between ICAM-1, sickle cells, and the endothelium, and discusses the potential of ICAM-1-targeted therapies for mitigating VOC and improving the quality of life for patients with SCD.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 6","pages":"730-737"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal Evolution in 207 Cases of Refractory or Relapsed Acute Myeloid Leukemia","authors":"Graeme F. Murray,&nbsp;Ian M. Bouligny,&nbsp;Thuy Ho,&nbsp;Juhi Gor,&nbsp;Kyle Zacholski,&nbsp;Nolan A. Wages,&nbsp;Steven Grant,&nbsp;Keri R. Maher","doi":"10.1111/ejh.14308","DOIUrl":"10.1111/ejh.14308","url":null,"abstract":"<div>\u0000 \u0000 <p>Clonal evolution (CE) is a driving force behind the development and progression of acute myeloid leukemia (AML). Advances in molecular and cytogenetic assays have improved the depth and breadth of detection of CE in AML, which is defined here as a detected change in cytogenetic or molecular profile at relapsed or refractory (RR) disease. In this study, we demonstrate the clinical impact of CE in a cohort of patients with RR AML treated between 2013 and 2023. We discovered CE is significantly more frequent in relapsed disease (58.2%, [46.6%, 69.2%]) than in refractory disease (21.1%, [14.4%, 29.2%], <i>p</i> &lt; 0.001). CE negatively impacts prognosis when detected by conventional karyotyping in refractory disease (4.2 vs. 13.9 months, <i>p</i> &lt; 0.011). In contrast with prior literature, CE had no impact on overall survival if detected in relapsed disease. Surprisingly, those who achieved negative measurable residual disease (MRD) were no more likely to eliminate their original clone than those who did not (<i>p</i> = 1). We found several cytogenetic and molecular signatures which may predispose to CE: aberrations of chromosome 17, trisomy 8, <i>TP53</i>, <i>KRAS</i>, and <i>FLT3</i>-TKD. Finally, physicians were less likely to retreat those with CE with IC after receiving IC as first-line therapy (35.0% vs. 70.9%, <i>p</i> = 0.004). This study illustrates the role of CE in chemotherapy-resistant AML; we identify unique cytogenetic and molecular signatures that define a subset of patients associated with a dismal prognosis. As next-generation sequencing panels expand and new methods to characterize cytogenetic abnormalities emerge, our findings establish a basis for future studies investigating the prognostic and therapeutic impact of CE.</p>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"98-104"},"PeriodicalIF":2.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}