HemaSphere最新文献

{"title":"MEK inhibition achieves robust and durable responses in Erdheim–Chester disease","authors":"Francesco Pegoraro,&nbsp;Félicien Triboulet,&nbsp;Matthias Papo,&nbsp;Francesco Peyronel,&nbsp;Anita Argentieri,&nbsp;Jerome Razanamahery,&nbsp;Ahmed Idbaih,&nbsp;Polyzois Makras,&nbsp;Ofer Shpilberg,&nbsp;Oshrat Hershkovitz-Rokah,&nbsp;Michael Girschikofsky,&nbsp;Matthew Collin,&nbsp;Kristian Bowles,&nbsp;Satyen H. Gohil,&nbsp;Rodothea Amerikanou,&nbsp;Emmanuel Ledoult,&nbsp;Tanguy Le Scornet,&nbsp;Mathilde de Menthon,&nbsp;Etienne Riviere,&nbsp;Xavier Boulu,&nbsp;Henry Dupuy,&nbsp;Achille Aouba,&nbsp;Stanislas Faguer,&nbsp;Xavier Solanich,&nbsp;Elena Sieni,&nbsp;Stéphane Barete,&nbsp;Chiara Bellino,&nbsp;Alessandro Tomelleri,&nbsp;Corrado Campochiaro,&nbsp;Lorenzo Dagna,&nbsp;Zahir Amoura,&nbsp;Jean-François Emile,&nbsp;Fleur Cohen-Aubart,&nbsp;Augusto Vaglio,&nbsp;Julien Haroche","doi":"10.1002/hem3.70499","DOIUrl":"10.1002/hem3.70499","url":null,"abstract":"<p>Erdheim–Chester disease (ECD) is a rare histiocytic neoplasm characterized by heterogeneous clinical manifestations and limited evidence to guide targeted therapy. While MEK inhibitors (MEKi) are increasingly used, data on their real-world efficacy, durability, and safety remain incomplete. We analyzed outcomes of patients with ECD treated with MEKi monotherapy across eight countries and assessed the dynamics and predictors of response, treatment retention, and the safety profile of MEKi. We included 170 patients and were able to evaluate response in 159 (94%) of them. Objective responses were observed in 112 patients (70%), disease stabilization in 35 (22%), and disease progression in 12 (8%). Response rates were independent of treatment lines and underlying molecular alterations. The median time to best response was 14 months, with an estimated 2-year probability of response of 61% (95% CI 51%–67%). In multivariable analysis, dyslipidemia (odds ratio [OR] 0.359, 95% CI 0.171–0.745) and neurodegeneration (OR 0.354, 95% CI 0.144–0.864) were associated with a lower probability of response to MEKi, while cutaneous and gastrointestinal involvement with a higher probability. After a median follow-up of 27 months (interquartile range [IQR] 12–57), the treatment retention rate was 76%, with most discontinuations attributable to toxicity. Adverse events were reported in 106 patients (62%) and were severe in 39 patients (23%). The estimated 2-year event-free survival was 65% (95% CI 57%–72%), and the estimated 2-year overall survival was 80% (95% CI 72%–86%). MEKi monotherapy provides robust and durable clinical efficacy in patients with ECD, with high response rates and favorable long-term outcomes, despite a substantial burden of toxicity.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108642","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":"EHA Guidelines on the management of children and adults with hemoglobin SC disease","authors":"David C. Rees,&nbsp;Valentine Brousse,&nbsp;Mariane de Montalembert,&nbsp;Bart J. Biemond,&nbsp;Lucia De Franceschi,&nbsp;Eugene Oteng-Ntim,&nbsp;Pagona Flevari,&nbsp;Valeria Pinto,&nbsp;John James,&nbsp;Elena Cela,&nbsp;Stefan Eber,&nbsp;Rachel Kesse-Adu,&nbsp;Jennifer Knight-Madden,&nbsp;France Pirenne,&nbsp;Aline Santin,&nbsp;Andreas Glenthøj","doi":"10.1002/hem3.70506","DOIUrl":"10.1002/hem3.70506","url":null,"abstract":"<p>HbSC disease is the second most common type of sickle cell disease (SCD) in populations of African origin. Although it is often grouped together with other types of SCD, particularly sickle cell anemia (HbSS), it has unique pathophysiology and a different spectrum of laboratory and clinical features. Compared to HbSS, hemoglobin levels are higher, HbF is lower at less than 5%, and most vaso-occlusive and vasculopathic complications are less frequent, although retinopathy is more common. Despite these differences, there have been no specific guidelines on the management of HbSC disease. This clinical practice guideline was developed by the European Hematology Association (EHA) in accordance with the EHA Guidelines Methodology Framework to provide consensus-based guidance for the management of children and adults with HbSC disease. A multidisciplinary Guideline Panel was convened by the EHA Guidelines Committee and included hematologists, pediatricians, methodologists, and patient representatives with expertise in SCD and its complications. Panel members were assigned to thematic working groups based on their clinical expertise, and each group was responsible for drafting content and recommendations within their respective domains. Literature searches were conducted using PubMed for relevant studies published in English. A modified Delphi process was used to reach consensus on recommendations, and panel members voted anonymously using an online system. A predefined threshold of ≥70% agreement and &lt;15% disagreement was required for adoption. Statements not reaching consensus were revised and subjected to further rounds of discussion and voting. Thirty-five recommendations were adopted, including guidance on the use of hydroxyurea and therapeutic venesection.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108660","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":"Integrating paroxysmal nocturnal hemoglobinuria (PNH) into mainstream hematological curriculum training","authors":"Morag Griffin,&nbsp;Richard Kelly,&nbsp;Colm Bradley,&nbsp;Sam Salek,&nbsp;Richard Soutar,&nbsp;Argiris Symeonidis","doi":"10.1002/hem3.70484","DOIUrl":"10.1002/hem3.70484","url":null,"abstract":"&lt;p&gt;Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-orphan life-threatening disorder characterized by chronic intravascular hemolysis (IVH) and thrombosis.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Prior to eculizumab approval, patients with PNH had a median survival of between 10 and 22 years&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; with thrombosis accounting for 22%–67% of death in case series and 29%–44% of patients having at least one event.&lt;span&gt;&lt;sup&gt;2, 4&lt;/sup&gt;&lt;/span&gt; Since the introduction of complement inhibitors, life expectancy in countries where treatment is available has nearly normalized.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; As symptoms of PNH can vary and are often non-specific, patients can present to a variety of medical specialties, leading to delays in diagnosis and appropriate treatment.&lt;/p&gt;&lt;p&gt;Here, we address issues around underdiagnosis and misdiagnosis of PNH and provide an evidence-based overview of current educational gaps and diagnostic challenges facing hematologists. We describe in more detail what the education, and ultimately the knowledge for clinical practice about PNH, of a trainee in hematology should include. This is an activity of the Gaucher Disease/Rare Disease Task Force, an independent Sub-Committee of the Granulocytes and Constitutional Marrow Failure Syndromes' Scientific Working Group of EHA, and the description which follows will be submitted for approval by the EHA Curriculum-Exam Committee.&lt;/p&gt;&lt;p&gt;Hematologists and scientists involved in PNH diagnosis and treatment need to be aware that the mutations which cause PNH are acquired in the PIGA gene, located on the X chromosome, at position p22.2. PIGA codes for glycophosphatidylinositol-anchored proteins, which include CD55 and CD59, both are negative regulators of complement activation. Men and women are equally affected by PNH, as PIGA mutations are acquired after lyonization. PNH usually presents in adults in their 30s, but can present at any age, including childhood.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; The prevalence of PNH with any clone size is 15.9 per million in Europe; this includes patients with small PNH clones, with other hematological conditions.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; Published/quoted prevalence data is often lower at 0.5–1.5 cases per million, due to the consideration of clinically significant PNH.&lt;/p&gt;&lt;p&gt;The complement system is part of the innate and adaptive immune response, designed to neutralize and destroy pathogens invading the systemic circulation. CD55 inhibits complement activation at complement protein C3b, and CD59 controls terminal complement activation. In PNH, loss of CD55 and CD59 results in uncontrolled complement activation and subsequent IVH, resulting in free hemoglobin release. Free hemoglobin is a nitric oxide scavenger leading to loss of smooth muscle relaxation and consequently to several PNH symptoms.&lt;/p&gt;&lt;p&gt;Some PNH blood cells have a partial CD55 and CD59 deficiency leading to complement inhibition reduction, whereas other cells have a complete deficiency with co","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108678","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":"A platform of serially transplantable AML PDX models covering subgroups for which no cell lines exist","authors":"Binje Vick,&nbsp;Vindi Jurinovic,&nbsp;Kristina Kuhbandner,&nbsp;Lena Lagally,&nbsp;Lisa Latzko,&nbsp;Chiara Arnreich,&nbsp;Gerulf Hänel,&nbsp;Amelie Muth,&nbsp;Maximilian Schönung,&nbsp;Arnold Kloos,&nbsp;Maja Rothenberg-Thurley,&nbsp;Annika M. Dufour,&nbsp;Stephanie Schneider,&nbsp;Lesca M. Holdt,&nbsp;Liliana Mura,&nbsp;Fabian Klein,&nbsp;Annette Frank,&nbsp;Dhruv Mehra,&nbsp;Annika Fröhlich,&nbsp;Johannes W. Bagnoli,&nbsp;Maya C. André,&nbsp;Claudia D. Baldus,&nbsp;Martin Carroll,&nbsp;Christine Dierks,&nbsp;Martin Ebinger,&nbsp;Katharina S. Götze,&nbsp;Pablo Menéndez,&nbsp;Christian Récher,&nbsp;Ambrine Sahal,&nbsp;Jean-Emmanuel Sarry,&nbsp;Christian Thiede,&nbsp;Talía Velasco-Hernández,&nbsp;Xiaoyan Wei,&nbsp;Jan H. Klusmann,&nbsp;Wolfgang Enard,&nbsp;Michael von Bergwelt-Baildon,&nbsp;Wolfgang Hiddemann,&nbsp;Klaus H. Metzeler,&nbsp;Philipp A. Greif,&nbsp;Michael Heuser,&nbsp;Daniel B. Lipka,&nbsp;Marion Subklewe,&nbsp;Sebastian Vosberg,&nbsp;Tobias Herold,&nbsp;Karsten Spiekermann,&nbsp;Irmela Jeremias","doi":"10.1002/hem3.70497","DOIUrl":"10.1002/hem3.70497","url":null,"abstract":"<p>Acute myeloid leukemia (AML) is a highly aggressive malignancy with poor prognosis, underlining the need for suitable model systems to develop novel treatments. To complement the few existing AML cell lines and restricted primografts, we transplanted more than 100 primary AML samples into immunocompromised mice and generated 23 exceptionally robust patient-derived xenograft (*PDX) models of AML that allow virtually unlimited serial transplantation and efficient genetic engineering. These models represent individuals of all age groups and several WHO subgroups. *PDX models substantially outperform AML cell lines in preserving leukemia biology and include AML subgroups for which no cell lines exist, such as cytogenetically normal or <i>IDH1/2</i>-mutant AML or simultaneous <i>NPM1</i> mutation and <i>FLT3-</i>ITD. Their resilience to freeze-thaw cycles supports broad dissemination across research institutions through sharing via CancerModels.org. Using lentiviruses, we stably expressed luciferase for longitudinal, noninvasive, and sensitive real-time monitoring of leukemia burden and therapeutic response <i>in vivo</i>. This approach enabled rigorously controlled preclinical studies, including phase II-like trials, which demonstrated highly variable treatment responses between different *PDX models, mimicking the heterogeneity in patient cohorts. Long-term treatment, including repeated cytarabine exposure over 1 year, showed a yet undescribed decrease in leukemia's proliferation rate. These insights underscore the platform's distinctive capacity to study treatment dynamics over clinically relevant timeframes. Collectively, our unique resource represents a powerful, robust, and versatile platform with strong potential to accelerate translational AML research for the ultimate benefit of patients.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108620","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":"Correction to “Combined inhibition of de novo pyrimidine synthesis and ATR promotes ATF4-mediated cell death in TP53-deficient ALL”","authors":"","doi":"10.1002/hem3.70502","DOIUrl":"10.1002/hem3.70502","url":null,"abstract":"<p>Grünewald KJT, Kes MMG, Stoll GR, et al. Combined inhibition of de novo pyrimidine synthesis and ATR promotes ATF4-mediated cell death in TP53-deficient ALL. <i>HemaSphere</i>. 2026;10(7):e70439. doi:10.1002/hem3.70439</p><p>In Figure 5, the abbreviation ATR was incorrectly defined as “Activating Transcription Factor 4” in the caption. The correct definition is “Ataxia Telangiectasia and Rad3-related (ATR) protein.”</p><p>We apologize for this error. The article has been corrected.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13636654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108669","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":"Longitudinal assessments of MRD in high-risk newly diagnosed transplant-ineligible multiple myeloma in the BENEFIT study (IFM2020-05)","authors":"Jill Corre,&nbsp;Jerome Lambert,&nbsp;Arthur Bobin,&nbsp;Salomon Manier,&nbsp;Aurore Perrot,&nbsp;Lionel Karlin,&nbsp;Murielle Roussel,&nbsp;Noemie Bigot,&nbsp;Omar Benbrahim,&nbsp;Olivier Allangba,&nbsp;Philippe Rey,&nbsp;Véronique Dorvaux,&nbsp;Marguerite Vignon,&nbsp;Virginie Roland,&nbsp;Réda Garidi,&nbsp;Jean-Noel Bastie,&nbsp;Marie-Lorraine Chretien,&nbsp;Sophie Godet,&nbsp;Lydia Montes,&nbsp;Brieuc Cherel,&nbsp;Anne Vekhoff,&nbsp;Thomas Chalopin,&nbsp;Borhane Slama,&nbsp;Kamel Laribi,&nbsp;Claire Dingremont,&nbsp;Christophe Roul,&nbsp;Valentine Richez-Olivier,&nbsp;Clara Mariette,&nbsp;Sophie Rigaudeau,&nbsp;Claire Calmettes,&nbsp;Mamoun Dib,&nbsp;Mourad Tiab,&nbsp;Laure Vincent,&nbsp;Jacques Delaunay,&nbsp;Sabrina Maheo,&nbsp;Anais Schavgoulidze,&nbsp;Laurent Frenzel,&nbsp;Pascal Godmer,&nbsp;Ronan Le Calloch,&nbsp;Emilie Chalayer,&nbsp;Helene Gardeney,&nbsp;Margaret Macro,&nbsp;Bruno Royer,&nbsp;Stephanie Harel,&nbsp;Olivier Decaux,&nbsp;Bertrand Arnulf,&nbsp;Karim Belhadj,&nbsp;Aurelie Gontier,&nbsp;Cyrille Touzeau,&nbsp;Mohamad Mohty,&nbsp;Philippe Moreau,&nbsp;Thierry Facon,&nbsp;Cyrille Hulin,&nbsp;Xavier Leleu","doi":"10.1002/hem3.70482","DOIUrl":"10.1002/hem3.70482","url":null,"abstract":"&lt;p&gt;The quadruplet-based regimens Isatuximab + VRd (bortezomib, lenalidomide, and dexamethasone) and Daratumumab + VRd have become the new standards of care for patients with newly diagnosed multiple myeloma transplant-ineligible (NDMM TI) over VRd based on IMROZ and CEPHEUS.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; The BENEFIT&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; study compared Isatuximab + VRd to Isatuximab + Rd to examine the role of the proteasome inhibitor bortezomib in this combination.&lt;/p&gt;&lt;p&gt;Patients with high-risk features (HRMM) benefit to a lesser extent from the discovery of new drugs for MM, with rapid loss of minimal residual disease (MRD) negativity rates and shorter survival times.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; In the BENEFIT study (ClinicalTrials.gov identifier: NCT04751877), the definition of HRMM was initially based on the Intergroupe Francophone du Myélome (IFM) linear predictor (LP) cytogenetic score model, in the absence of an international consensus definition.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; A recent international genomic consensus staging (GCS) (International Myeloma Society [IMS]/International Myeloma Working Group [IMWG]) has standardized the definition of HRMM based on a next-generation sequencing (NGS)-based definition plus serum beta-2-microglobulin level, to enable cross-study comparisons.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;We aimed to investigate the MRD rates&lt;span&gt;&lt;sup&gt;8, 9&lt;/sup&gt;&lt;/span&gt; of Isa-VRd compared to IsaRd in HRMM in the BENEFIT study overall, and also its safety profile using the recent GCS definition for HRMM.&lt;/p&gt;&lt;p&gt;BENEFIT is a Phase 3 trial sponsored by CHU (Centre Hospitalier Universitaire) Poitiers, France, in collaboration with the Intergroupe Francophone of Myeloma (IFM), that randomly assigned NDMM TI, aged 65–79 years, to Isa-VRd or IsaRd until progression. MRD was centrally determined by NGS with a 10&lt;sup&gt;−6&lt;/sup&gt; sensitivity (Professor Avet Loiseau/Professor Corre, Toulouse Oncopole, France) and was performed at 12, 18, and 24 months, and yearly thereafter on bone marrow aspiration in patients who achieved at least a partial response (≥PR).&lt;span&gt;&lt;sup&gt;10-12&lt;/sup&gt;&lt;/span&gt; In BENEFIT, no patient in PR only depth of response had obtained MRD-negative status. We started to observe MRD-negative status only in patients with VGPR or better response.&lt;/p&gt;&lt;p&gt;Three patients were studied using multiparametric flow cytometry (MFC) with a 10&lt;sup&gt;−5&lt;/sup&gt; sensitivity, and if MRD was 10&lt;sup&gt;−5&lt;/sup&gt; negative, they were always classified as 10&lt;sup&gt;−6&lt;/sup&gt; positive. The sustained MRD negativity rate at 10&lt;sup&gt;−5&lt;/sup&gt; was defined as the proportion of patients with MRD-negative 10&lt;sup&gt;–5&lt;/sup&gt; results over 12 months (between Months 12 and 24), without any MRD-positive results in between (Month 18).&lt;/p&gt;&lt;p&gt;Patients who were not identified as having HRMM at diagnosis and developed relapse within 18 months from diagnosis were classed as FHR.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;HRMM was found in 72/270 (27%) patients using GCS, and 42/135 (31%) and 30/135 (22%) ","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108681","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":"Abstracts of 14th International Symposium on Hodgkin Lymphoma","authors":"","doi":"10.1002/hem3.70490","DOIUrl":"https://doi.org/10.1002/hem3.70490","url":null,"abstract":"&lt;p&gt;&lt;span&gt;Tara Cochrane&lt;/span&gt;&lt;sup&gt;1;2&lt;/sup&gt;, Sze Ting Lee&lt;sup&gt;3&lt;/sup&gt;, Robin Gasiorowski&lt;sup&gt;4;5&lt;/sup&gt;, Shane A. Gangatharan&lt;sup&gt;6;7&lt;/sup&gt;, Fernando Roncolato&lt;sup&gt;8&lt;/sup&gt;, William Ep Renwick&lt;sup&gt;9;10&lt;/sup&gt;, Jock Simpson&lt;sup&gt;11;12&lt;/sup&gt;, Amanda Johnston&lt;sup&gt;13&lt;/sup&gt;, Uwe Hahn&lt;sup&gt;14;15&lt;/sup&gt;, Philip Wong&lt;sup&gt;16;17&lt;/sup&gt;, Masa Lasica&lt;sup&gt;18&lt;/sup&gt;, Ann Solterbeck&lt;sup&gt;19&lt;/sup&gt;, Robert Traficante&lt;sup&gt;19&lt;/sup&gt;, Sally Mapp&lt;sup&gt;20;21&lt;/sup&gt;, Bianca Devitt&lt;sup&gt;22;23&lt;/sup&gt;, Dhvani Pandya&lt;sup&gt;24&lt;/sup&gt;, Julia Carlson&lt;sup&gt;24&lt;/sup&gt;, Tracey Gerber&lt;sup&gt;24&lt;/sup&gt;, Mark Hertzberg&lt;sup&gt;25&lt;/sup&gt;, Eliza Hawkes&lt;sup&gt;26;27&lt;/sup&gt;, Colm Keane&lt;sup&gt;20;28&lt;/sup&gt;&lt;/p&gt;&lt;p&gt;&lt;sup&gt;1&lt;/sup&gt;Gold Coast University Hospital, Southport, Queensland, Australia, &lt;sup&gt;2&lt;/sup&gt;Griffith University, School of Medicine and Dentistry, Griffith Health, Nathan, Australia, &lt;sup&gt;3&lt;/sup&gt;Dept of Molecular Imaging and Therapy, Austin Health, Melbourne, Australia, &lt;sup&gt;4&lt;/sup&gt;Concord Hospital, Sydney, Australia, &lt;sup&gt;5&lt;/sup&gt;University of Sydney, Australia, &lt;sup&gt;6&lt;/sup&gt;Fiona Stanley Hospital, Murdoch, Australia, &lt;sup&gt;7&lt;/sup&gt;University of Western Australia, Crawley, Australia, &lt;sup&gt;8&lt;/sup&gt;St George Hospital, Sydney, Australia, &lt;sup&gt;9&lt;/sup&gt;Western Health, Footscray, Australia, &lt;sup&gt;10&lt;/sup&gt;University of Melbourne, Melbourne Australia, &lt;sup&gt;11&lt;/sup&gt;Mid North Coast Cancer Institute, Port MacQuarie, Australia, &lt;sup&gt;12&lt;/sup&gt;University of UNSW, Sydney, Australia, &lt;sup&gt;13&lt;/sup&gt;Westmead Hospital, Sydney, Australia, &lt;sup&gt;14&lt;/sup&gt;Royal Adelaide Hospital and The Queen Elizabeth Hospital, Adelaide Australia, &lt;sup&gt;15&lt;/sup&gt;SA Pathology, Adelaide, Australia, &lt;sup&gt;16&lt;/sup&gt;Toowoomba Hospital, Toowoomba, Australia, &lt;sup&gt;17&lt;/sup&gt;University of Queensland, Rural Clinical School, Brisbane, Australia, &lt;sup&gt;18&lt;/sup&gt;St Vincent's Hospital, Melbourne, Australia, &lt;sup&gt;19&lt;/sup&gt;Statistical Revelations Pty Ltd, Ocean Grove, Australia, &lt;sup&gt;20&lt;/sup&gt;Princess Alexandra Hospital, Brisbane, Australia, &lt;sup&gt;21&lt;/sup&gt;University of Queensland, Faculty of Medicine, Brisbane, Australia, &lt;sup&gt;22&lt;/sup&gt;Eastern Health, Oncology, Box Hill, Australia, &lt;sup&gt;23&lt;/sup&gt;Monash University Eastern Health Clinical School, Melbourne, Australia, &lt;sup&gt;24&lt;/sup&gt;Australasian Lymphoma and Leukaemia Group, Melbourne Australia, &lt;sup&gt;25&lt;/sup&gt;Prince of Wales Hospital, Randwick, Australia, &lt;sup&gt;26&lt;/sup&gt;Olivia Newton John Cancer Research Institute at Austin Health, Melbourne, Australia, &lt;sup&gt;27&lt;/sup&gt;Monash University, School of Public Health and Preventive Medicine, Melbourne, Australia, &lt;sup&gt;28&lt;/sup&gt;University of Queensland, Frazer Institute, Brisbane, Australia&lt;/p&gt;&lt;p&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Figure 1:&lt;/b&gt; 2-year PFS and OS of the entire HD12 cohort.&lt;/p&gt;&lt;p&gt;Anti-PD-1 therapy with Adriamycin, vinblastine, dacarbazine (AVD) is effective in older patients (pts) with cHL with limited data in those ≥70 years. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) is active in older cHL pts but has not been combined with anti-PD-1.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; CATER-HL (ALLG-HD12) is a single arm phase","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 S2","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70490","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149099797","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":"One cycle of nelarabine given after induction is well tolerated but does not improve outcome in adults with T-cell precursor acute lymphoblastic leukemia: Outcome data from the UKALL14 randomized-controlled trial","authors":"Clare J. Rowntree,&nbsp;Amy A. Kirkwood,&nbsp;Nadine Farah,&nbsp;Emma Lawrie,&nbsp;David I. Marks,&nbsp;Andrew K. McMillan,&nbsp;Tobias F. Menne,&nbsp;Anthony V. Moorman,&nbsp;Bela Patel,&nbsp;Pip Patrick,&nbsp;Paul Smith,&nbsp;Krisztina Z. Alapi,&nbsp;Lingyi Wang,&nbsp;Marc R. Mansour,&nbsp;Adele K. Fielding","doi":"10.1002/hem3.70480","DOIUrl":"10.1002/hem3.70480","url":null,"abstract":"<p>UKALL14 (NCT01085617) T-cell arm was a phase 3, randomized-controlled trial. Adults aged 25–65 years were randomized 1:1 at entry to receive standard of care (SOC) or SOC + nelarabine 1.5 g/m² (Days 1, 3, and 5) to be administered following second induction. The primary end-point was event-free survival (EFS). From 2011 to 2018, 143 patients were randomly assigned to SOC (<i>N</i> = 75) or SOC + nelarabine (<i>N</i> = 68). There was no significant difference in EFS between the treatment groups; HR 0.86 (95% CI 0.52–1.43) P = 0.57, EFS: 58.2% SOC versus 62.7% SOC + nelarabine. The severe adverse events and nonrelapse mortality rates did not differ between the arms; in particular, there was no difference in grade 3–4 neurotoxicity. The 3-year cumulative incidence of relapse was 31% in the SOC arm versus 28.9% in the SOC+ nelarabine arm. Forty of 44 relapses (90.9%) occurred within 2 years of randomization; the median survival postrelapse was 5.7 months, with no difference by arm. Diagnostic samples were analyzed for level of differentiation arrest by analysis of the TCRg locus to detect the most immature cases through absence of biallelic TCRg deletion (ABD). There was a trend toward more relapses with ABD (37.3%) versus no ABD (19.5%), P = 0.066. Diagnostic samples (<i>N</i> = 133) were analyzed for mutations in <i>NOTCH1, FBXW7, NRAS, KRAS,</i> and <i>PTEN</i>, with no significant differences in CR rates or survival in patients with wild-type (WT) <i>NOTCH1</i> or <i>FBXW7</i>. The 12 patients with <i>NRAS</i> mutations had significantly inferior CR and EFS compared to patients with wild-type <i>NRAS</i>.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108654","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":"Integrating Gaucher disease (GD) into mainstream hematological curriculum training","authors":"Colm Bradley,&nbsp;Argiris Symeonidis,&nbsp;Sam Salek,&nbsp;Nkemdirim Jacob","doi":"10.1002/hem3.70474","DOIUrl":"10.1002/hem3.70474","url":null,"abstract":"&lt;p&gt;Gaucher disease (GD) is the most common lysosomal storage disorder and arises from pathogenic variants in &lt;i&gt;GBA1&lt;/i&gt; that reduce glucocerebrosidase activity, leading to lysosomal accumulation of glucosylceramide and related metabolites in macrophages.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Although rare, GD has major relevance to hematology because many of its earliest and most persistent manifestations fall within routine hematology practice, including splenomegaly, anemia, thrombocytopenia, bleeding symptoms, marrow infiltration, paraproteinemia, and skeletal complications that may mimic malignant or inflammatory disease.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Delayed diagnosis remains common, and surveys suggest that awareness among hematologists is better than in some other specialties but still incomplete, especially when disease presents atypically or with mild phenotypes.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; This creates a strong case for formal integration of GD into mainstream hematology training.&lt;/p&gt;&lt;p&gt;The purpose of this editorial is to define the core knowledge and clinical competencies that hematology trainees should acquire. The emphasis is not that every hematologist must become a GD subspecialist, but that all should be able to recognize when to suspect the disease, request appropriate first-line investigations, interpret key laboratory and imaging findings, understand modern treatment principles, and work effectively with specialist centers. This is particularly important in Europe, where training standards are increasingly harmonized and where rare disease diagnosis depends on shared awareness rather than isolated expertise.&lt;/p&gt;&lt;p&gt;Trainees should understand the basic biochemistry and cell biology of membrane sphingolipids, lysosomal degradation pathways, and the role of glucocerebrosidase and its cofactors, including saposin C.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; They should know that hundreds of pathogenic &lt;i&gt;GBA1&lt;/i&gt; variants exist, that genotype influences phenotype, but does not fully determine it, and that common variants, such as N370S and L444P differ in their typical clinical associations.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Knowledge of lysosomal dysfunction is clinically relevant because substrate accumulation and secondary metabolites, such as glucosylsphingosine contribute to chronic inflammation, immune dysregulation, osteoclast activation, coagulation abnormalities, and neurodegeneration. Macrophage activation is central to disease pathophysiology, affecting the liver, spleen, bone marrow, and, in some forms, the nervous system and lungs.&lt;/p&gt;&lt;p&gt;Hematologists should know that GD is pan-ethnic but enriched in Ashkenazi Jewish populations and is substantially underdiagnosed worldwide, particularly in milder type 1 disease.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Classical clinical classification distinguishes type 1 (nonneuronopathic), type 2 (acute neuronopathic), and type 3 (chronic neuronopathic) disease, but clinicians should also recognize perinatal lethal presentations, hydrops fetal","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108647","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":"SLV-404, an anti-RYK antibody–drug conjugate, is effective in Richter transformation patient-derived xenografts","authors":"Matilde Micillo,&nbsp;Beatrice Pirajno,&nbsp;Francesco Edoardo Vallone,&nbsp;Victor Navarro-Tableros,&nbsp;Elisabetta Bolli,&nbsp;Valentina Griggio,&nbsp;Brian J. Lannutti,&nbsp;Katti A. Jessen,&nbsp;Tiziana Vaisitti,&nbsp;Silvia Deaglio","doi":"10.1002/hem3.70478","DOIUrl":"10.1002/hem3.70478","url":null,"abstract":"<p>Richter transformation (RT), a highly aggressive lymphoma arising from a preexisting chronic lymphocytic leukemia, represents a major unmet clinical need. Recent data have shown that an antibody–drug conjugate (ADC) targeting the cell-surface pseudokinase ROR1 is effective in RT patients. In this work, we explored other members of the ROR1 family and focused on RYK as a novel therapeutic target. Transcriptomic analyses revealed that RYK is expressed across multiple lymphoma subtypes, including indolent and aggressive lymphomas, such as RT, while it is absent in peripheral blood mononuclear cells (PBMCs) from healthy donors. To increase the selectivity of the ADC for highly proliferating B-cell malignancies, as a payload we chose an inhibitor of topoisomerase I (TOP1), which is highly expressed in aggressive lymphomas while being undetectable in PBMCs from healthy donors. Based on these premises, we generated SLV-404, an ADC composed of a chimeric antibody directed against the extracellular domain of RYK, a cleavable linker, and the potent TOP1 inhibitor deruxtecan (DXd). <i>In vitro</i> studies in lymphoma cell lines and in cells obtained from RT patient-derived xenografts (RT-PDXs) consistently showed robust induction of apoptosis following SLV-404 treatment, while normal PBMCs were fully resistant. The antitumor activity of SLV-404 was then confirmed <i>in vivo</i> using subcutaneous and intravenous RT-PDX models. Treated animals survived significantly longer with markedly reduced tumor growth and tumor burden. Together, these findings identify RYK as a therapeutic target in aggressive RT and underline the potential of SLV-404 as an ADC-based strategy for the treatment of aggressive lymphomas.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108657","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}