HemaSphere最新文献

{"title":"Caplacizumab treatment in elderly patients with iTTP: Experience from the Spanish TTP Registry","authors":"Inés Gómez-Seguí,&nbsp;Joan Cid,&nbsp;Miquel Lozano,&nbsp;Maria Eva Mingot-Castellano,&nbsp;Cristina Pascual-Izquierdo,&nbsp;Luz Maria Gonzalez del Castillo,&nbsp;Julia Maria Vidan Estevez,&nbsp;Faustino Garcia-Candel,&nbsp;Moraima Jiménez Balarezo,&nbsp;David Valcarcel,&nbsp;Clara Cuellar Perez-Avila,&nbsp;Maria Arraiz Ramirez,&nbsp;Sunil Lakhwani,&nbsp;Maria Gemma Moreno Jimenez,&nbsp;Ana Yurena Oliva Hernandez,&nbsp;Jose Maria Garcia Gala,&nbsp;Jorge Martinez Nieto,&nbsp;Rosa Goterris,&nbsp;Marta Fernández Docampo,&nbsp;Clara Sopeña Pell-Ilderton,&nbsp;Javier de la Rubia","doi":"10.1002/hem3.70109","DOIUrl":"https://doi.org/10.1002/hem3.70109","url":null,"abstract":"<p>Immune thrombotic thrombocytopenic purpura (iTTP) typically affects middle-aged individuals, although it sometimes appears in older patients. Caplacizumab is approved for the treatment of iTTP, but information on the safety and efficacy of this drug in elderly patients is not available. We aimed to analyze the management and outcomes of iTTP patients registered in the Spanish TTP Registry and receiving caplacizumab at any time during the acute episode, focusing on patients ≥60 years (<i>n</i> = 29) and comparing them with patients &lt;60 years (<i>n</i> = 70). Severe bleeding motivated caplacizumab's initiation delay in one patient ≥60 years. Patients receiving anticoagulation or antiplatelet therapy at diagnosis were more common in older patients (10% vs. 1%; <i>p</i> = 0.074), as well as the occurrence of bleeding motivating caplacizumab discontinuation (17% vs. 1%, respectively; <i>p</i> = 0.008). Caplacizumab seemed to be efficient in the treatment of iTTP in older patients, reducing refractoriness and death to 3% and exacerbation to 10%, similar to younger patients. The higher risk of bleeding in this older population warrants the need for close monitoring during treatment and to further explore the best management of thrombotic and bleeding risk.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-derived xenografts: Practical considerations for preclinical drug testing","authors":"Charles E. de Bock","doi":"10.1002/hem3.70133","DOIUrl":"https://doi.org/10.1002/hem3.70133","url":null,"abstract":"&lt;p&gt;Patient-derived xenografts (PDXs) are increasingly being used to test new therapies or repurpose existing therapies as researchers and clinicians optimize precision oncology treatments.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This has been further accelerated with the increasing availability of new immunodeficient mice that have improved our ability to generate a wider variety of PDXs, including for challenging leukemia subtypes such as favorable risk acute myeloid leukemia (AML). Inspired by the conversation with Prof Richard Lock who features in a &lt;i&gt;HemaSphere&lt;/i&gt; podcast reflecting on over 20 years of experience in preclinical testing,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; this article reflects some of the practical considerations for establishing a PDX bank and their use in evaluating new therapies.&lt;/p&gt;&lt;p&gt;Immunodeficient mice provide the opportunity to engraft human leukemia cells and generate a PDX model. These are the models of systemic disease that infiltrate the bone marrow, spleen, and liver and disseminate throughout the peripheral blood. They are attractive models because they retain the cellular and molecular characteristics of the original disease with leukemia burden monitored through peripheral blood sampling or via bioluminescence.&lt;/p&gt;&lt;p&gt;To establish a PDX, patient cells are injected into the tail vein or intrafemorally of immunodeficient mice (Figure 1). This first round of engraftment or primagrafts usually has the slowest kinetics of engraftment time depending on the quality and source of the patient sample. Once leukemia develops in these primagrafts, the cells can be harvested from highly engrafted mice (e.g., human CD45+ve cells &gt; 80% in the peripheral blood) and serially reinjected into secondary and tertiary recipients after which the kinetics of engraftment stabilises and is usually consistent across multiple transplants.&lt;/p&gt;&lt;p&gt;Importantly, when establishing new PDX samples, it is recommended that cells harvested from primagraft, and secondary transplant cells are protected and stored over the long term with only cells from tertiary transplants used in downstream experiments. This will ensure the longevity of the PDX bank and provide an important reference for quality assurance regarding clonal and genetic heterogeneity.&lt;/p&gt;&lt;p&gt;Alongside the technical establishment of the PDX, ensuring excellent record keeping (e.g., the time taken to reach 1% human CD45 cells in the peripheral blood) and adhering to the published minimum information standards for PDX models is important for the field in terms of reproducibility and sharing of PDX resources.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; This includes metadata on the original patient sample and sequencing methodology for the molecular characterization of the PDX (Figure 1). This characterization of the PDX is essential for downstream preclinical drug testing when individual samples are chosen based on the expression or a biomarker or the presence of a genetic mutation.&lt;/p&gt;&lt;p&gt;It is equally important that PDX samples","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delving deeper into the pathogenesis and genomics of posttransplant diffuse large B-cell lymphoma","authors":"Flore Sneyers,&nbsp;Ana-Lucía Rocha-Iraizos,&nbsp;Vibeke K. J. Vergote,&nbsp;Daan Dierickx","doi":"10.1002/hem3.70123","DOIUrl":"https://doi.org/10.1002/hem3.70123","url":null,"abstract":"<p>Posttransplant lymphoproliferative disorders (PTLDs) are a well-known complication of solid organ transplantation and allogeneic hematopoietic stem cell transplantation. The diffuse large B-cell lymphoma subtype (PT-DLBCL) is the most frequent monomorphic PTLD and is associated with poor prognosis. Transplant recipients have an increased risk of abnormal proliferation of lymphoid cells because of diminished immune surveillance. In about 60% of the cases, Epstein–Barr virus infection seems to contribute to the cancer phenotype. Although clinical and research interest in the disorder has increased during the last two decades, the pathology of the disease remains largely elusive. In this review, we summarize current knowledge of PT-DLBCL pathogenesis, and we discuss how a better understanding of PT-DLBCL can lead to improved diagnostics and therapeutic strategies.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimal residual disease assessment following CD19-targeted therapy in B-cell precursor acute lymphoblastic leukemia using standardized 12-color flow cytometry: A EuroFlow study","authors":"Martijn W. C. Verbeek,&nbsp;Michaela Reiterová,&nbsp;Anna Laqua,&nbsp;Beatriz Soriano Rodríguez,&nbsp;Lukasz Sedek,&nbsp;Chiara Buracchi,&nbsp;Malicorne Buysse,&nbsp;Elen Oliveira,&nbsp;Robby Engelmann,&nbsp;Joana Desterro,&nbsp;Anja X. De Jong,&nbsp;Sebastian Boettcher,&nbsp;Romana Jugooa,&nbsp;Susana Barrena,&nbsp;Saskia Kohlscheen,&nbsp;Stefan Nierkens,&nbsp;Joana G. Rodriques,&nbsp;Mattias Hofmans,&nbsp;Giuseppe Gaipa,&nbsp;Elaine Sobral de Costa,&nbsp;Ester Mejstrikova,&nbsp;Tomasz Szczepanski,&nbsp;Monika Brüggemann,&nbsp;Jacques J. M. van Dongen,&nbsp;Alberto Orfao,&nbsp;Vincent H. J. van der Velden","doi":"10.1002/hem3.70125","DOIUrl":"https://doi.org/10.1002/hem3.70125","url":null,"abstract":"<p>Detection of minimal/measurable residual disease (MRD) is a critical prognostic marker in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The EuroFlow Consortium previously developed an 8-color flow cytometric MRD protocol, effective for &gt;98% of BCP-ALL patients treated with chemotherapy. This study aimed to enhance MRD detection, particularly for patients treated with CD19-targeted therapies, by expanding the EuroFlow protocol to a 12-color panel. This new panel incorporates additional B-cell markers and exclusion T/NK-cell markers (CD3 and CD7). Through an evaluation of 237 diagnostic BCP-ALL samples, CD22, CD24, and HLA-DR were selected as additional B-cell gating markers. Two 12-color tubes were technically optimized and clinically validated across 101 patient follow-up samples, demonstrating excellent concordance with molecular MRD levels (<i>R</i>² = 0.88). The 12-color BCP-ALL MRD tubes were compatible with the previously developed 8-color automated gating and identification (AGI) tool and demonstrated good reproducibility. Our findings indicate that the 12-color panel performs comparably to the 8-color BCP-ALL MRD panel, including both CD19-positive and CD19-negative cases. However, it offers an improved definition of the B-cell lineage, particularly for expert-guided manual data analysis, and provides additional information on the expression of the targetable marker CD22.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved post-transplant outcomes since 2000 for Ph-positive acute lymphoblastic leukemia in first remission: A study from the EBMT Acute Leukemia Working Party","authors":"Ali Bazarbachi,&nbsp;Myriam Labopin,&nbsp;Iman Abou Dalle,&nbsp;Ibrahim Yakoub-Agha,&nbsp;Gérard Socié,&nbsp;Thomas Schroeder,&nbsp;Didier Blaise,&nbsp;Xavier Poiré,&nbsp;Marie Balsat,&nbsp;Urpu Salmenniemi,&nbsp;Nicolaus Kröger,&nbsp;Alexander Kulagin,&nbsp;Eva Maria Wagner-Drouet,&nbsp;Depei Wu,&nbsp;Eolia Brissot,&nbsp;Arnon Nagler,&nbsp;Sebastian Giebel,&nbsp;Fabio Ciceri,&nbsp;Mohamad Mohty","doi":"10.1002/hem3.70117","DOIUrl":"https://doi.org/10.1002/hem3.70117","url":null,"abstract":"<p>Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in their first complete remission (CR1). Recent results using the combination of blinatumomab and second- or third-generation tyrosine kinase inhibitors have challenged the necessity of allo-HCT in CR1. Here we assessed real-world changes over time in transplant characteristics and outcomes in adult patients with Ph+ ALL in CR1, using a large dataset from the European Society for Blood and Marrow Transplantation registry. A total of 3292 patients (45% female; median age 45 years) who underwent allo-HCT from 2001 to 2020 were included. Over four periods (2001–2005, 2006–2010, 2011–2015, and 2016–2020), the 3-year cumulative incidence of relapse decreased from 41% to 19%, and non-relapse mortality decreased from 25% to 17% (<i>p</i> &lt; 0.001 for both). Correspondingly, 3-year leukemia-free survival (LFS) improved from 34% to 64%, and overall survival (OS) from 47% to 75% (<i>p</i> &lt; 0.001 for both). Graft versus host disease-free and relapse-free survival also improved from 26% to 49% (<i>p</i> &lt; 0.001). Factors negatively affecting LFS included older age, male gender, male donor and measurable residual disease (MRD) positivity pre-transplant, while total body conditioning (TBI) positively affected LFS. OS was positively influenced by younger age, female gender, matched sibling donor, TBI, and T cell depletion. Importantly, improvement in post-transplant outcomes over time was observed regardless of pre-transplant MRD status. In conclusion, we observed an impressive improvement over time in post-transplant outcomes of Ph+ ALL. These large-scale data can serve as a benchmark for future studies.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NGS-MRD negativity in post-HSCT ALL spares unnecessary therapeutic interventions triggered by borderline qPCR results without an increase in relapse risk","authors":"Krystof Seferna,&nbsp;Michael Svaton,&nbsp;Andrea Rennerova,&nbsp;Aneta Skotnicova,&nbsp;Leona Reznickova,&nbsp;Tatana Valova,&nbsp;Petr Sedlacek,&nbsp;Petr Riha,&nbsp;Renata Formankova,&nbsp;Petra Keslova,&nbsp;Lucie Sramkova,&nbsp;Jan Stary,&nbsp;Jan Zuna,&nbsp;Alexandra Kolenova,&nbsp;Cyril Salek,&nbsp;Jan Trka,&nbsp;Eva Fronkova","doi":"10.1002/hem3.70124","DOIUrl":"https://doi.org/10.1002/hem3.70124","url":null,"abstract":"<p>Monitoring of minimal residual disease (MRD) after hematopoietic stem cell transplantation (HSCT) in patients with acute lymphoblastic leukemia (ALL) is vital for timely therapeutic intervention planning. However, interpreting low-positive results from the current standard method, quantitative PCR (qPCR) of immunoglobulin and T-cell receptor gene rearrangements (IG/TR), poses challenges due to the risk of false positivity caused by non-specific amplification. We aimed to improve MRD detection specificity using the next-generation amplicon sequencing (NGS) of IG/TR rearrangements for better relapse prediction. In pediatric and young adult ALL patients undergoing sequential post-HSCT MRD monitoring, we prospectively re-tested positive non-quantifiable qPCR results with NGS-MRD using the EuroClonality-NGS approach. We were able to confirm 13 out of 47 (27.7%) qPCR positive results using the more specific NGS-MRD method. Out of 10 patients with at least one MRD positivity confirmed by NGS, six relapsed (60%) 1–3.7 months after testing. Among 25 patients with all NGS-MRD results negative, two relapses occurred (8%) after 5.1 and 12.1 months. One-year RFS was 40% versus 96% and 3-year OS was 33.3% versus 94.4% for the NGS-positive and NGS-negative groups, respectively. The difference was not attributable to a varying rate of therapeutic interventions. Six patients out of 14 who had immunosuppressive treatment tapered or received donor lymphocyte infusion in response to MRD positivity developed significant graft versus host disease, leading to one fatality. This underscores the importance of enhancing the post-HSCT relapse risk prediction accuracy through NGS-MRD testing to avoid unnecessary interventions.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation science in hemato-oncology molecular diagnostics in France via the Groupe des Biologistes Moléculaire des Hémopathies Malignes (GBMHM)","authors":"Jean-Michel Cayuela,&nbsp;Pierre Sujobert,&nbsp;Pascale Flandrin-Gresta,&nbsp;Anne-Sophie Alary,&nbsp;Carole Maute,&nbsp;Damien Luque-Paz,&nbsp;Cédric Pastoret,&nbsp;Stéphanie Dulucq,&nbsp;Audrey Gauthier,&nbsp;Meryl Darlington,&nbsp;Isabelle Durand-Zaleski,&nbsp;Olivier Kosmider,&nbsp;Elizabeth Macintyre","doi":"10.1002/hem3.70121","DOIUrl":"https://doi.org/10.1002/hem3.70121","url":null,"abstract":"&lt;p&gt;Implementation science in health has been defined as the study of methods to promote the adoption and integration of evidence-based practices, interventions, and policies into routine health care and public health settings.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Such approaches are essential to optimize societal benefit from published evidence-based innovation. In the case of hematological malignancies (HMs), the exponential increase in molecular genetic testing comes with challenges to offer them to all patients. Different attempts have been developed in European countries but in a heterogeneous fashion depending on a variety of factors.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In France, members of the French Hematology Society (&lt;i&gt;Société Française d'Hématologie&lt;/i&gt;, SFH) created in 2005 the association of molecular biologists for HMs (&lt;i&gt;Groupe des Biologistes Moléculaires des Hémopathies Malignes&lt;/i&gt;, GBMHM), a non-profit scientific network that organizes continuing medical education, concerted actions, and external quality assessment (EQA) for molecular diagnostics of hematological cancers. Most GBMHM activities represent implementation scientific approaches, designed to optimize molecular hematology at a national level. The present report summarizes these activities, as a contribution to adaptation of the 2017/746 In Vitro Diagnostic Medical Devices Regulation (IVDR).&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The GBMHM EQA system started in 2005 with the help of national health care authorities, which were eager to sustain innovative biology while respecting performance and safety issues. We initially piloted four tests for a national EQA program within the aforementioned RuBIH1 program (BCR::ABL1 transcript detection and quantification, JAK2&lt;sup&gt;V617F&lt;/sup&gt; detection, and IG/TR lymphoid clonality assessment). The successful pilot was then incremented with 12 other programs, as detailed.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; From 2014 onward, the program has been financed by billing participating health institutions. EQA is based on two principles: (1) sample exchange campaigns, and (2) feedback meetings for the promotion of standardization and ongoing medical education.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; To ensure full objectivity, the organization of sample exchange campaigns, including evaluation of results, is managed by a university hospital-based not-for-profit platform, employing non-GBMHM members, but with feedback meetings organized with GBMHM experts, often those involved in corresponding European standardization.&lt;/p&gt;&lt;p&gt;It should be noted that a certain degree of post-market device evaluation, such as the GeneXpert for &lt;i&gt;BCR::ABL1&lt;/i&gt; quantification, is also addressed through sample exchange campaigns. This approach is used for both CE-IVD (e.g., &lt;i&gt;JAK2&lt;/i&gt;&lt;sup&gt;V617F&lt;/sup&gt; and lymphoid clonality) and in-house tests (the majority, and all rare targets). This approach has produced clear improvements, including superior analytical performance, technical standardization, and homogenization o","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver iron concentration thresholds: Where do they really come from?","authors":"Lukas Müller,&nbsp;Diego Hernando,&nbsp;Moniba Nazeef,&nbsp;Scott B. Reeder","doi":"10.1002/hem3.70122","DOIUrl":"https://doi.org/10.1002/hem3.70122","url":null,"abstract":"&lt;p&gt;Systemic iron overload arises from a variety of causes, including genetic disorders of iron absorption, repeated blood transfusions, hemolytic anemias, hematologic malignancies, and chronic liver disease, among others.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The body lacks mechanisms for active elimination of excess iron, leading to accumulation in the liver, spleen, pancreas, endocrine glands, bone marrow, and heart. Excess iron is toxic and leads to organ dysfunction and early mortality, typically from heart failure or end-stage liver disease.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Treatment for iron overload aims to prevent complications through therapeutic phlebotomy or chelation, depending on the underlying etiology.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Early detection and quantification of total body iron (TBI) stores are critical for timely intervention before irreversible damage occurs. Importantly, phlebotomy and chelation have notable side effects and high costs.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; For these reasons, accurate monitoring of TBI is essential to initiate and monitor treatment. Although serum ferritin (SF) is the simplest means to assess TBI, it is an acute phase reactant often confounded by unrelated factors and may not accurately reflect TBI. Moreover, up to 30% of patients exhibit a discrepancy in their response to chelation therapy as assessed by changes in SF and liver iron concentration (LIC).&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Importantly, TBI is linearly and highly correlated with LIC. LIC is widely accepted as a surrogate of TBI,&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; and its accurate measurement leads to informed objective management strategies.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; For this reason, LIC measurement is included in current guidelines for the surveillance and treatment of systemic iron overload.&lt;span&gt;&lt;sup&gt;1, 2, 8&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Historically, LIC has been assessed using non-targeted biopsy combined with spectrophotometric assays.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; LIC can be reported interchangeably as milligrams of iron per gram of dry liver tissue (mg Fe/g dry, or mg/g) or micromoles of iron per gram of dry tissue (μmol Fe/g dry, or μmol/g).&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Although biopsy is accepted as the reference to assess LIC, it is invasive and expensive, suffers from sampling variability, and is contraindicated in patients with bleeding diatheses.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt; Fortunately, LIC can be assessed noninvasively with high accuracy and precision using state-of-the-art magnetic resonance imaging (MRI).&lt;span&gt;&lt;sup&gt;2, 6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;St Pierre et al.&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt; summarized LIC thresholds as follows: &lt;1.8 mg/g, normal; 3.2 mg/g, the lower limit of the optimal range for chelation therapy; 7.0 mg/g, the upper limit of the optimal range for chelation therapy; &gt;7.0 mg/g, increased risk of complications including liver fibrosis and diabetes; &gt;15.0 mg/g, greatly increased risk for cardiac disease and early death. Current patient management guidelines rely","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatocyte Toll-like receptors contribute to the hepcidin inflammatory response to pathogens and pathogen-derived ligands","authors":"Katharina Bonitz,&nbsp;Silvia Colucci,&nbsp;Ruiyue Qiu,&nbsp;Sandro Altamura,&nbsp;Richard Sparla,&nbsp;Katja Mudder,&nbsp;Stefan Zimmermann,&nbsp;Matthias W. Hentze,&nbsp;Martina U. Muckenthaler,&nbsp;Oriana Marques","doi":"10.1002/hem3.70096","DOIUrl":"https://doi.org/10.1002/hem3.70096","url":null,"abstract":"<p>Iron restriction is a critical pathomechanism underlying the Anemia of Inflammation and an innate immune response limiting the replication of extracellular pathogens. During infections, innate immune cells detect pathogen-associated molecular patterns (PAMPs) and produce proinflammatory cytokines. Among these, interleukin (IL)-6 is detected by hepatocytes, where it activates the production of the iron-regulated hormone hepcidin that inhibits iron export from macrophages. Consequently, macrophages accumulate iron and hypoferremia (low plasma iron) develops. Whether Toll-like receptors (TLRs) expressed on hepatocytes directly recognize PAMPs and contribute to hepcidin upregulation is still an open question. Stimulation of primary murine hepatocytes with a panel of PAMPs targeting TLRs 1–9 revealed that the TLR5 ligand flagellin and the TLR2:TLR6 ligand FSL1 upregulated hepcidin. Hepcidin was also induced upon treatment with heat-killed <i>Staphylococcus aureus</i> (HKSA) and <i>Brucella abortus</i> (HKBA). The hepcidin response to flagellin, FSL1, HKSA, and HKBA started at an early time point, was independent of autocrine regulation by IL-6, and occurred through the TLR-mitogen-activated protein kinase (MAPK) axis. By analyzing a macrophage:hepatocyte co-culture, we additionally show that the hepcidin response was dependent on TLR2:TLR6 expression in hepatocytes and independent of macrophage cytokine secretion. Ex vivo liver perfusion of mice with FSL1 and HKSA further revealed that PAMPs and pathogens can pass the sinusoidal barrier and reach hepatocytes to cause hepcidin upregulation in a TLR2:TLR6-dependent manner. We conclude that hepatocytes can directly recognize PAMPs and pathogens and promote hepcidin upregulation in a macrophage and cytokine-independent manner. This positions hepatocytes in the spotlight as potential direct drivers of iron restriction.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-dose therapy followed by autologous stem cell transplantation emerges as the preferred salvage therapy in patients with limited-stage Hodgkin lymphoma progressing/relapsing after initial therapy: A subset analysis of the EORTC/LYSA/FIL H10 trial","authors":"Gotti Manuel,&nbsp;Yana Stepanishyna,&nbsp;Tetiana Skrypets,&nbsp;Luigi Marcheselli,&nbsp;Caterina Cristinelli,&nbsp;Barbara Botto,&nbsp;Sanne Tonino,&nbsp;Doriane Cavalieri,&nbsp;Alessandro Pulsoni,&nbsp;Martin Hutchings,&nbsp;Mohammad Hammoud,&nbsp;Catherine Fortpied,&nbsp;Luigi Rigacci,&nbsp;Wouter Plattel,&nbsp;Marc André,&nbsp;Massimo Federico","doi":"10.1002/hem3.70105","DOIUrl":"https://doi.org/10.1002/hem3.70105","url":null,"abstract":"&lt;p&gt;Long-term survival of patients with limited-stage classical Hodgkin lymphoma (cHL) is excellent, with more than 90% surviving and disease-free for 10 years after diagnosis and initial treatment.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Nevertheless, improving patient outcomes and minimizing the risk of long-term toxicities continue to be priorities.&lt;/p&gt;&lt;p&gt;Early response assessment with positron emission tomography (ePET) is an important predictor of outcomes, and several trials have focused on response-adapted treatments to avoid the need for radiotherapy (RT) in patients with an early complete metabolic response. In the EORTC/LYSA/FIL H10 intergroup randomized trial, such a response-adapted strategy resulted in the achievement of 95% overall survival at 10 years.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; However, in the 1419 cases with updated follow-up, 106 progressions or recurrences (7.5%) were recorded.&lt;/p&gt;&lt;p&gt;In this study, we report the results of a detailed analysis of second-line treatment choices and outcomes in these 106 patients. Previously untreated patients aged 15–70 years with classic supradiaphragmatic stage I or II cHL were eligible for the EORTC/LYSA/FIL H10 trial. Both favorable (F) and unfavorable (U) patients according to the EORTC criteria were included. All patients received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), after which an ePET was performed. The primary objective of this study was to evaluate whether involved-node RT could be omitted without loss of efficacy in ePET-negative patients.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; This long-term analysis was restricted to the subset of patients with progression/recurrence after study entry. The principal endpoints of this analysis were survival after recurrence (SAR) and progression-free survival after recurrence (PFS2). From November 2006 to June 2011, 1950 patients were enrolled in the EORTC/LYSA/FIL H10 trial by 158 institutions, in which 1925 completed two ABVD cycles and performed an ePET scan. Long-term follow-up has been updated for 1419 of these patients (Supporting Information S3: Data Supplement Figure 1).&lt;/p&gt;&lt;p&gt;Overall, 106 (7.5%) events were recorded, including 17 progressions (events within 6 months from study entry, 1.2%) and 89 recurrences (6.3%). Ninety-five events occurred in this study population before the safety amendment, and 11 thereafter. Patients' characteristics and outcomes for the entire cohort are summarized in Table 1.&lt;/p&gt;&lt;p&gt;Events occurred in 5.5% (28/508), 6.5% (42/651), and 13.8% (36/260) of patients with early favorable ePET-, early unfavorable ePET-, and ePET-positive disease, respectively.&lt;/p&gt;&lt;p&gt;Sites of progression/recurrence were recorded in 32 (30.2%) patients with initially involved and non-irradiated sites, 12 (11.3%) involved and irradiated, 45 (42.4%) not initially involved and not irradiated, and 17 (16.0%) not involved but irradiated sites. The 17 progressions occurred after a median of 4.4 months from study entry (range 2.1–6.0 months).","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}