HemaSphere最新文献

{"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}

{"title":"H1-0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape in preleukemia and B cell acute lymphoblastic leukemia","authors":"Vera H. Jepsen,&nbsp;Andrea Hanel,&nbsp;Daniel Picard,&nbsp;Rigveda Bhave,&nbsp;Rebecca Hasselmann,&nbsp;Juha Mehtonen,&nbsp;Julian Schliehe-Diecks,&nbsp;Carla-Johanna Kath,&nbsp;Vithusan Suppiyar,&nbsp;Yash Prasad,&nbsp;Katerina Schaal,&nbsp;Jia-Wey Tu,&nbsp;Nadine Rüchel,&nbsp;Ersen Kameri,&nbsp;Nan Qin,&nbsp;Herui Wang,&nbsp;Zhengping Zhuang,&nbsp;Rabea Wagener,&nbsp;Lena Blümel,&nbsp;Tobias Lautwein,&nbsp;Daniel Hein,&nbsp;David Koppstein,&nbsp;Gesine Kögler,&nbsp;Marc Remke,&nbsp;Sanil Bhatia,&nbsp;Merja Heinäniemi,&nbsp;Arndt Borkhardt,&nbsp;Ute Fischer","doi":"10.1002/hem3.70116","DOIUrl":"https://doi.org/10.1002/hem3.70116","url":null,"abstract":"<p><i>ETV6::RUNX1</i>, the most common oncogenic fusion in pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL), induces a clinically silent preleukemic state that can persist in carriers for over a decade and may progress to overt leukemia upon acquisition of secondary lesions. The mechanisms contributing to quiescence of <i>ETV6::RUNX1</i>+ preleukemic cells still remain elusive. In this study, we identify linker histone H1-0 as a critical mediator of the <i>ETV6::RUNX1</i>+ preleukemic state by employing human\u0000<span>-</span>induced pluripotent stem cell (hiPSC) models engineered by using CRISPR/Cas9 gene editing. Global gene expression analysis revealed upregulation of <i>H1-0</i> in <i>ETV6::RUNX1</i>+ hiPSCs that was preserved upon hematopoietic differentiation. Moreover, whole transcriptome data of 1,727 leukemia patient samples showed significantly elevated <i>H1-0</i> levels in <i>ETV6::RUNX1</i>+ BCP-ALL compared to other leukemia entities. Using dual-luciferase promoter assays, we show that ETV6::RUNX1 induces <i>H1-0</i> promoter activity. We further demonstrate that depletion of H1-0 specifically inhibits ETV6::RUNX1 signature genes, including <i>RAG1</i> and <i>EPOR</i>. Single-cell sequencing showed that <i>H1-0</i> is highly expressed in quiescent hematopoietic cells. Importantly, H1-0 protein levels correspond to susceptibility of BCP-ALL cells towards histone deacetylase inhibitors (HDACis) and combinatorial treatment using the H1-0-inducing HDACi Quisinostat showed promising synergism with established chemotherapeutic drugs. Taken together, our data identify H1-0 as a key regulator of the <i>ETV6::RUNX1</i>+ transcriptome and indicate that the addition of Quisinostat may be beneficial to target non-responsive or relapsing <i>ETV6::RUNX1</i>+ BCP-ALL.</p>","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/hem3.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749453","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":"TP53 deletion as an MRD-dependent risk factor in childhood B-ALL: A post hoc analysis from a prospective cohort","authors":"Yangyang Gao,&nbsp;Jun Li,&nbsp;Ning Wang,&nbsp;Wenbin An,&nbsp;Zixi Yin,&nbsp;Junxia Wang,&nbsp;Xia Chen,&nbsp;Yumei Chen,&nbsp;Ye Guo,&nbsp;Wenyu Yang,&nbsp;Li Zhang,&nbsp;Yao Zou,&nbsp;Xiaojuan Chen,&nbsp;Xiaofan Zhu","doi":"10.1002/hem3.70115","DOIUrl":"https://doi.org/10.1002/hem3.70115","url":null,"abstract":"<p>The effect of <i>TP53</i> alterations on childhood B-cell acute lymphoblastic leukemia (B-ALL) remains unclear. To investigate the prognostic value of <i>TP53</i> deletion (<i>TP53</i>^<i>del</i>) and <i>TP53</i> mutation (<i>TP53</i>^<i>mut</i>), this post hoc study used fluorescence in situ hybridization test to detect <i>TP53</i>^<i>del</i> in 907 newly diagnosed B-ALL patients from a prospective cohort of Chinese Children's Cancer Group ALL-2015 trial. Targeted gene sequencing was used to identify <i>TP53</i>^<i>mut</i> in 342 out of the 907 patients. <i>TP53</i>^<i>del</i> was detected in 4.4% of patients. The frequency of hypodiploidy was higher in <i>TP53</i>^<i>del</i> subgroup (7.5% vs. 0.5%, <i>p</i> = 0.002), but patients with <i>TP53</i>^<i>del</i> were less likely to have other recurrent genetic abnormalities, including <i>BCR::ABL1, ETV6::RUNX1, TCF3::PBX1 and KMT2A</i> rearrangements. Univariable and multivariable analyses indicated that <i>TP53</i>^<i>del</i> was an independent risk factor for overall survival (OS) and disease-free survival (DFS). Furthermore, stratification analysis revealed that <i>TP53</i>^<i>del</i> was associated with lower 5-year DFS in patients with positive minimal residual disease (MRD) after induction in the intermediate-risk group (0.0% vs. 58.0% [95% confidence interval [CI] 49.2%–68.3%], <i>p</i> &lt; 0.001), suggesting an MRD-dependent pattern. However, somatic <i>TP53</i>^<i>mut</i> was not associated with poor survival (81.8% [95% CI 61.9%–100.0%] vs. 84.9% [95% CI 81.1%-89.0%], <i>p</i> = 0.971). In summary, <i>TP53</i>^<i>del</i> may serve as a predictor for poor prognosis in pediatric B-ALL. In particular, children in the intermediate-risk group with positive MRD and <i>TP53</i>^<i>del</i> may require more aggressive treatment.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741648","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 Cancer Organisation Essential Requirements for Quality Cancer Care: Hematological malignancies","authors":"John G. Gribben,&nbsp;Leticia Quintanilla-Martinez,&nbsp;Simon Crompton,&nbsp;Jann Arends,&nbsp;Christophe Bardin,&nbsp;Heiko Becker,&nbsp;Frederic Castinetti,&nbsp;Dégi L. Csaba,&nbsp;Melvin D'Anastasi,&nbsp;Thomas Frese,&nbsp;Jan Geissler,&nbsp;Reda Matuzeviciene,&nbsp;Marius E. Mayerhoefer,&nbsp;Rui Medeiros,&nbsp;Kate Morgan,&nbsp;Šarūnas Narbutas,&nbsp;Samantha Nier,&nbsp;Umberto Ricardi,&nbsp;Eugenia Trigoso Arjona,&nbsp;Mehmet Ungan,&nbsp;Lorna Warwick,&nbsp;Emanuele Zucca","doi":"10.1002/hem3.70108","DOIUrl":"https://doi.org/10.1002/hem3.70108","url":null,"abstract":"&lt;p&gt;European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCCs) are primarily organizational recommendations, giving politicians, managers, oncology teams, patients, and patient advocacy groups a non-technical overview of the elements needed to provide high-quality care throughout the patient journey. They are not clinical guidelines, but define the actions necessary to deliver high-quality care to patients with specific cancer types, here applied to hematological malignancies in Europe.&lt;/p&gt;&lt;p&gt;The recommendations set out an aspirational but realistic standard that should be within reach for most countries, given adequate resourcing. They include the need for (1) fast and easy access to accurate diagnostic tests; (2) clearly established pathways for referral to specialist centers; (3) services to be centralized; (4) continuous monitoring of patient well-being; (5) treatment strategies to be agreed by a core multidisciplinary team; and (6) patients and their families to be involved at all stages of decision-making.&lt;/p&gt;&lt;p&gt;The foundation of ERQCCs is quality. This has become increasingly important in all aspects of healthcare as new and complex treatments come into use and pressure grows on resources. Improving quality means delivering cancer care that is timely, safe, effective, and efficient; that puts the patient at the center; and that gives all people in Europe equal access to high-quality services.&lt;/p&gt;&lt;p&gt;Variations in cancer outcomes and disparities in management and funding across Europe make quality frameworks essential.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The European Guide on Quality Improvement in Comprehensive Cancer Control (2017) underscored this fact, recommending comprehensive cancer centers and integrated care networks.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; However, while some progress has been made in concentrating expertise for specific tumor types such as breast and prostate cancers, dedicated multidisciplinary units are lacking for most cancers, including hematological malignancies. Recent initiatives such as Europe's Beating Cancer Plan have added a new momentum to quality initiatives, emphasizing multidisciplinary collaboration and timely access to quality treatment, aligning closely with ERQCC principles.&lt;/p&gt;&lt;p&gt;Hematological malignancies (blood cancers) are the fifth most common cancer group in economically developed regions. They include leukemias, lymphomas, and myelomas, with over 100 clinically meaningful subtypes defined by the World Health Organization's Classification of Tumours of Haematopoietic and Lymphoid Tissues and the International Consensus Classification.&lt;span&gt;&lt;sup&gt;3-6&lt;/sup&gt;&lt;/span&gt; The European Society for Medical Oncology (ESMO) and the European Hematology Association (EHA) have issued clinical practice guidelines for many of the subtypes and these are regularly updated.&lt;/p&gt;&lt;p&gt;The European-Commission-funded HAEMACARE project has produced crude, age-specific, and age-standardized incidence rates for hematologic","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741649","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}