HemaSphere最新文献

{"title":"A German multicenter real-world analysis of talquetamab in 138 patients with relapsed/refractory multiple myeloma","authors":"Jan H. Frenking,&nbsp;Christine Riedhammer,&nbsp;Raphael Teipel,&nbsp;Florian Bassermann,&nbsp;Britta Besemer,&nbsp;Moritz Bewarder,&nbsp;Jan Braune,&nbsp;Annamaria Brioli,&nbsp;Franziska Brunner,&nbsp;Maria Dampmann,&nbsp;Roland Fenk,&nbsp;Deniz N. Gezer,&nbsp;Sarah Goldman-Mazur,&nbsp;Christine Hanoun,&nbsp;Marion Högner,&nbsp;Cyrus Khandanpour,&nbsp;Katja Kolditz,&nbsp;Igor Kos,&nbsp;Jan Krönke,&nbsp;Miriam Kull,&nbsp;Valentine Landrin,&nbsp;Theo Leitner,&nbsp;Maximilian Merz,&nbsp;Ivana von Metzler,&nbsp;Christian S. Michel,&nbsp;Carsten Müller-Tidow,&nbsp;Sebastian Theurich,&nbsp;Karolin Trautmann-Grill,&nbsp;Ralph Wäsch,&nbsp;Romans Zukovs,&nbsp;Mathias Hänel,&nbsp;Leo Rasche,&nbsp;Marc S. Raab","doi":"10.1002/hem3.70114","DOIUrl":"https://doi.org/10.1002/hem3.70114","url":null,"abstract":"<p>Bispecific T-cell engagers (BTCEs) represent a paradigm shift in the treatment of relapsed/refractory multiple myeloma (RRMM). Talquetamab, a GPRC5DxCD3 BTCE, has shown promising results in the MonumenTAL-1 trial and was recently approved by the Food and Drug Administration and the European Medicines Agency. However, treatment under real-world conditions may not represent patient characteristics in clinical trials with restricted enrollment criteria. We performed a retrospective real-world analysis including 138 RRMM patients treated with talquetamab at 21 German centers. Of evaluable patients, 43% had ISS stage III, 37% had extraosseous disease, and 48% had high-risk cytogenetics. After a median of six prior therapy lines, 58% of patients would not have been eligible for MonumenTAL-1. With a median follow-up of 8.2 months, we observed an overall response rate of 65% and a median progression-free survival of 6.4 months (95% confidence interval 5.1–9.0). Prior BTCE exposure, ISS stage III, extraosseous disease, and penta-drug refractory disease were associated with unfavorable outcomes. Grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 5.1% and 1.5% of patients, respectively. In summary, our real-world study confirms the efficacy and safety of talquetamab, despite a high proportion of patient- and disease-related risk factors. These results support its use as bridging or long-term treatment, even in advanced stages.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840668","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":"European guidelines on treatment and supportive measures in chronic neutropenias: A consensus between the European Hematology Association and the EuNet-INNOCHRON COST Action based on a systematic evidence review","authors":"Francesca Fioredda,&nbsp;Michail Spanoudakis,&nbsp;Julia Skokowa,&nbsp;Hannah Tamary,&nbsp;Piero Farruggia,&nbsp;Antonio Almeida,&nbsp;Daniela Guardo,&nbsp;Jan Palmblad,&nbsp;Petter Höglund,&nbsp;Ivo P. Touw,&nbsp;Cornelia Zeidler,&nbsp;Alan J. Warren,&nbsp;Mario Csenar,&nbsp;Nicole Skoetz,&nbsp;Elio Castagnola,&nbsp;Erica Ricci,&nbsp;David C. Dale,&nbsp;Peter E. Newburger,&nbsp;Karl Welte,&nbsp;Helen A. Papadaki,&nbsp;Carlo Dufour","doi":"10.1002/hem3.70113","DOIUrl":"https://doi.org/10.1002/hem3.70113","url":null,"abstract":"<p>The treatment of chronic neutropenias and control of neutropenia-related infections remain challenging topics for pediatric and adult hematologists. This article aims to fill the gap in the treatment of neutropenias and, in combination with the previously published European guidelines on diagnosis of neutropenias, gives complete and comprehensive guidance on the whole management of patients with neutropenia. In terms of methodology, an Evidence-Based Medicine team produced an evidence synthesis of the literature on the treatment of neutropenias. Then, according to the robustness of the evidence, consensus recommendations were elaborated and voted by an expert's panel from the Cooperation in Science and Technology European Network for the Innovative Diagnosis and Treatment of Chronic Neutropenias (https://eunet-innochron.eu/) and the Specialized Working Group on Granulocytes and Constitutional Bone Marrow Failure Syndromes of the European Hematology Association. Whenever evidence was not available, recommendations were based on the expert's panel opinion. Consensus-based recommendations are related to granulocyte colony-stimulating factor indications and schedule of administration, indications for hematopoietic stem cell transplantation, supportive treatments and measures, and new treatments that have been evolving over the recent years. These guidelines, rather than a numerical correction of the absolute neutrophil count, suggest a holistic, patient-centered approach aiming at optimizing the management of chronic neutropenic patients and offering valuable and practical guidance to the hematologists for their daily clinical practice.</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/hem3.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836196","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":"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":"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}