HemaSphere最新文献

{"title":"Allele burden expansion in JAK2V617F and CALR-mutated myeloproliferative neoplasms predicts disease progression and is associated with anagrelide treatment","authors":"Zi Yun Ng, Laurane Cottin, Marine Demoy, Damien Luque Paz, Corentin Orvain, Wayne-Corentin Lambert, Jean-Christophe Ianotto, Eric Lippert, David M. Ross, Diana Iarossi, Alesia Khan, Daniel Lock, Catherine Truong, Kamel Laribi, Yun Fan Yang, Laura Li Gagnon, Valerie Ugo, Claire N. Harrison, Jennifer O'Sullivan","doi":"10.1002/hem3.70460","DOIUrl":"10.1002/hem3.70460","url":null,"abstract":"<p>Recent prospective studies demonstrated that reductions in <i>JAK2</i><sup>V617F</sup> variant allele frequency (VAF) correlate with clinical benefit in essential thrombocythemia (ET) and polycythemia vera (PV).<span><sup>1, 2</sup></span> However, the impact of <i>CALR</i> VAF dynamics with therapy on clinical outcomes remains relatively unknown. Pegylated interferon-alpha (IFN) has been shown to variably reduce <i>CALR</i> VAF, but changes with treatments such as hydroxycarbamide (HC), anagrelide (ANA), and ruxolitinib (RUX), a JAK inhibitor, are less well described.<span><sup>3</sup></span> Newer mutation-targeted therapies are demonstrating early significant reductions in VAFs, which may serve as a surrogate marker of disease modification.<span><sup>4</sup></span></p><p>We therefore sought to evaluate dynamics of driver mutation VAF in myeloproliferative neoplasm (MPN) patients treated with cytoreductive therapies and correlate these with clinical outcomes. Sequential cases were collated from eight international centers including the prospective MAJIC-ET study.<span><sup>5</sup></span> Although MAJIC-ET has been reported, inclusion enabled greater power for time-dependent outcomes. A comparator cohort of <i>JAK2</i><sup>V617F</sup>-mutated patients was included; the MAJIC-PV cohort was excluded due to substantially higher baseline VAF precluding meaningful comparison. <i>CALR</i> VAF was quantified using next-generation sequencing (NGS), fragment analysis, or droplet digital polymerase chain reaction (ddPCR). <i>JAK2</i><sup>V617F</sup> VAF was quantified using quantitative PCR or NGS. Serial VAF measurements within each patient were performed using the same analytical platform at the same center throughout follow-up. Molecular response (MR), comprising complete (CMR) and partial (PMR) response as defined per IWG-MRT/ELN 2013 criteria, plus an exploratory PMR20 category, is detailed in Supporting Information S2: Supplementary Methods.<span><sup>6-8</sup></span></p><p>Overall, 347 patients with <i>CALR</i> (<i>n</i> = 190) and <i>JAK2</i><sup>V617F</sup> (<i>n</i> = 157) mutations with VAF measurements at two timepoints at least 6 months apart were included (Table 1). ET was the most prevalent diagnosis (<i>n</i> = 235, 67.7%), followed by primary and secondary myelofibrosis (MF; <i>n</i> = 73, 21.1%), prefibrotic myelofibrosis (<i>n</i> = 17, 4.9%), PV (<i>n</i> = 15, 4.3%), MPN-unclassified (<i>n</i> = 6, 1.7%), and blast-phase MPN (<i>n</i> = 1, 0.3%). Treatment was defined as the predominant cytoreductive agent active between the first and second VAF measurements (Supporting Information S2: Supplementary Methods). Treatments included IFN (<i>n</i> = 132, 38.0%), RUX (<i>n</i> = 70, 20.2%), ANA (<i>n</i> = 29, 8.4%), HC (<i>n</i> = 88, 25.4%), and other therapies (<i>n</i> = 28, 8.0%) (Table 1). Median VAF measurement interval was 54 months (range 6–246), median follow-up 123 months (range 8–469), and median treatment duration was 55 mon","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 9","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864154","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":"AI for prognostic assessment of diffuse large B-cell lymphoma using H&E whole-slide images","authors":"Jonas Lippl,&nbsp;Sarah Reinke,&nbsp;Stefan Schrod,&nbsp;Lukas Wolfseher,&nbsp;Paul Hüttl,&nbsp;Michael Huttner,&nbsp;Annette M. Staiger,&nbsp;Ilske Oschlies,&nbsp;Karoline Koch,&nbsp;Edward G. Michaelis,&nbsp;Julia Richter,&nbsp;Hilka Rauert-Wunderlich,&nbsp;Nicole Seifert,&nbsp;Robin Kosch,&nbsp;Norbert Schmitz,&nbsp;Marita Ziepert,&nbsp;Lorenz Thurner,&nbsp;Viola Poeschel,&nbsp;Bertram Glaß,&nbsp;Lorenz Trümper,&nbsp;Gerhard Held,&nbsp;David W. Scott,&nbsp;Andreas Rosenwald,&nbsp;German Ott,&nbsp;Rainer Spang,&nbsp;Michael Altenbuchinger,&nbsp;Wolfram Klapper","doi":"10.1002/hem3.70463","DOIUrl":"10.1002/hem3.70463","url":null,"abstract":"<p>Prediction of the outcome of large B-cell lymphomas/high-grade B-cell lymphomas (DLBCLs/HGBCLs) is based on clinical parameters and molecular testing, for example, for rearrangements of MYC (MYC-R) and MYC-R in combination with BCL2 and BCL6 translocations (double/triple hit). However, the group of DLBCL/HGBCL with poor outcome is not confined to MYC-R lymphomas, and fluorescence in situ hybridization (FISH) testing for MYC-R misses several high-risk lymphomas. We aimed to understand if artificial intelligence (AI) trained to identify MYC-R will delineate a poor prognostic subgroup. We generated a collection of digital hematoxylin and eosin (H&amp;E)-stained slides of DLBCL/HGBCL (<i>N</i> = 2018) annotated for MYC, BCL2, and BCL6 translocations. A multiple-instance deep learning AI model for the identification of MYC-R alone or as double/triple hit was established using 1035 H&amp;E-stained slides and evaluated on an external test cohort (<i>N</i> = 499). A pretrained tumor tissue classifier improved reliability and interpretability by focusing the model on tumor areas. Our model score reflects a morphological “MYCness” in DLBCL/HGBCL and demonstrates a strong association with overall survival (OS) and progression-free survival (PFS) in the external test cohort. This was confirmed with an additional clinical test cohort (<i>N</i> = 484) without FISH labels. The AI model scores correlate with various molecular features of DLBCL/HGBCL, including BCL2 and MYC gene expression, and the high-grade gene expression signature, but also features of the tumor microenvironment. Multivariate analysis, adjusted for International Prognostic Index (IPI) factors, demonstrated the prognostic significance of our model in identifying high-risk cases for both PFS and OS.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 9","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864151","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":"Machine learning provides individualized prediction of outcomes after first complete remission without allo-HSCT consolidation in adult acute myeloid leukemia—A HARMONY study","authors":"Alberto Hernández-Sánchez,&nbsp;Javier Martínez Elicegui,&nbsp;Eric Sträng,&nbsp;Axel Benner,&nbsp;Marta Sobas,&nbsp;Ángela Villaverde Ramiro,&nbsp;Amin T. Turki,&nbsp;María Abáigar,&nbsp;Gastone Castellani,&nbsp;Jurjen Versluis,&nbsp;Ian Thomas,&nbsp;Jesse M. Tettero,&nbsp;Rabea Mecklenbrauck,&nbsp;Joaquín Martínez-López,&nbsp;Marta Pratcorona,&nbsp;Guillermo Sanz,&nbsp;Maria Teresa Voso,&nbsp;Sören Lehmann,&nbsp;Christoph Röllig,&nbsp;Klaus H. Metzeler,&nbsp;Konstanze Döhner,&nbsp;Michael Heuser,&nbsp;Torsten Haferlach,&nbsp;Peter J. M. Valk,&nbsp;Jesús María Hernández-Rivas,&nbsp;Brian J. P. Huntly,&nbsp;Gert Ossenkoppele,&nbsp;Hartmut Döhner,&nbsp;Lars Bullinger","doi":"10.1002/hem3.70461","DOIUrl":"https://doi.org/10.1002/hem3.70461","url":null,"abstract":"<p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment option for a significant proportion of patients with acute myeloid leukemia (AML), and it is generally recommended when the relapse risk without allo-HSCT outweighs the estimated non-relapse mortality significantly. While current recommendations for allo-HSCT are based on risk groups, there is considerable heterogeneity within these individual categories. We analyzed 2550 intensively treated AML patients aged 18–70 with cytogenetic and next-generation sequencing data from the HARMONY Alliance database, who did not receive allo-HSCT in first complete remission (CR1). A non-parametric machine learning (ML) model based on Bayesian Additive Regression Trees (BART) integrated clinical variables and genomic aberrations to provide individualized outcome estimations. External validation was performed in a cohort of 714 patients enrolled in UK-NCRI trials. The predictive performance of the HARMONY ML model, measured by the area under the time-dependent receiver operating curve (AUC(t)), was superior to European LeukemiaNet (ELN)2022 risk classification in estimating 5-year overall survival (0.741 vs. 0.700), 5-year relapse-free survival (0.752 vs. 0.705), and 5-year cumulative incidence of relapse (0.742 vs. 0.708), which was confirmed in the external validation cohort. Notably, the model revealed substantial heterogeneity within ELN2022 risk groups, identifying a significant proportion of favorable-risk patients with a predicted 5-year CIR &gt; 40%, who could potentially benefit from allo-HSCT in CR1. The HARMONY ML model provides individualized risk prediction in intensively treated adult AML patients and supports more tailored therapeutic decisions regarding allo-HSCT in CR1, which should be further advanced by integrating measurable residual disease in the future.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 9","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148856731","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":"Somatic RUNX1 exonic deletions in myelodysplastic syndrome: A rare yet high-risk recurrent genetic aberration","authors":"Ahmed Al-Djaber,&nbsp;Albin Österroos,&nbsp;Alessandro Baldi,&nbsp;Arielle R. Munters,&nbsp;Nikolaj Juul Nitschke,&nbsp;Klas Raaschou-Jensen,&nbsp;Claudia Schöllkopf,&nbsp;Marianne Tang Severinsen,&nbsp;Tatjana Pandzic,&nbsp;Manja Meggendorfer,&nbsp;Joachim Weischenfeldt,&nbsp;Anne Stidsholt Roug,&nbsp;Kirsten Grønbæk,&nbsp;Claes Ladenvall,&nbsp;Torsten Haferlach,&nbsp;Claudia Haferlach,&nbsp;Thale Kristin Olsen,&nbsp;Panagiotis Baliakas","doi":"10.1002/hem3.70452","DOIUrl":"https://doi.org/10.1002/hem3.70452","url":null,"abstract":"&lt;p&gt;Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders characterized by significant genetic and clinical heterogeneity.&lt;span&gt;&lt;sup&gt;1-3&lt;/sup&gt;&lt;/span&gt; Risk stratification and therapeutic decision-making are increasingly guided by the underlying genomic landscape.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; Mutations in the runt-related transcription factor 1 (&lt;i&gt;RUNX1&lt;/i&gt;) gene are observed in 10%–15% of all de novo MDS cases and are among the most well-established prognostic molecular markers in MDS and myeloid neoplasms (MNs).&lt;span&gt;&lt;sup&gt;6-11&lt;/sup&gt;&lt;/span&gt; RUNX1 is a transcription factor essential for normal hematopoiesis, acting as a master regulator of hematopoietic stem cell maintenance, lineage commitment, and megakaryopoiesis.&lt;span&gt;&lt;sup&gt;12, 13&lt;/sup&gt;&lt;/span&gt; Most &lt;i&gt;RUNX1&lt;/i&gt; mutations cause loss-of-function and are associated with specific clinico-biological features.&lt;span&gt;&lt;sup&gt;14&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;We recently reported that somatic &lt;i&gt;RUNX1&lt;/i&gt; exonic deletions (RUNX1&lt;sup&gt;del&lt;/sup&gt;) are recurrent and associated with a poor prognosis in acute myeloid leukemia (AML).&lt;span&gt;&lt;sup&gt;15&lt;/sup&gt;&lt;/span&gt; In addition, the spectrum of reported germline &lt;i&gt;RUNX1&lt;/i&gt; mutations includes a substantial proportion of gross and intragenic exonic deletions, likely underdiagnosed in the past due to technical limitations.&lt;span&gt;&lt;sup&gt;16-18&lt;/sup&gt;&lt;/span&gt; Prompted by these facts, we hypothesized that somatic RUNX1&lt;sup&gt;del&lt;/sup&gt; may be present in MDS.&lt;/p&gt;&lt;p&gt;We analyzed a cohort of 1299 MDS patients using a comprehensive diagnostic approach that included whole-genome sequencing (WGS, &lt;i&gt;n&lt;/i&gt; = 263), array comparative genomic hybridization (CGH, &lt;i&gt;n&lt;/i&gt; = 584), and an in-house next-generation sequencing (NGS) panel (&lt;i&gt;n&lt;/i&gt; = 85) or a combination of the three methods (&lt;i&gt;n&lt;/i&gt; = 367), allowing reliable detection of RUNX1&lt;sup&gt;del&lt;/sup&gt;. Methodological details are described in Supporting Information S1: Supplementary Methods.&lt;/p&gt;&lt;p&gt;Patient characteristics are described in Supporting Information S2: Table 1. Twenty-five (1.9%) patients had &lt;i&gt;RUNX1&lt;/i&gt; deletions (RUNX1&lt;sup&gt;del&lt;/sup&gt;), 121 (9.3%) had &lt;i&gt;RUNX1&lt;/i&gt; mutations (RUNX1&lt;sup&gt;mut&lt;/sup&gt;), and 1153 (88.8%) had no &lt;i&gt;RUNX1&lt;/i&gt; aberration (RUNX1&lt;sup&gt;wt&lt;/sup&gt;). Three of the RUNX1&lt;sup&gt;mut&lt;/sup&gt; patients also had a concurrent &lt;i&gt;RUNX1&lt;/i&gt; deletion. The final cohort had a median age of 73 years (range 23–94 years) with 756 (58.2%) men.&lt;/p&gt;&lt;p&gt;Diagnostic categorization by WHO 2017&lt;span&gt;&lt;sup&gt;19&lt;/sup&gt;&lt;/span&gt; was available for 1242 (95.6%) patients (Supporting Information S2: Table 1). RUNX1&lt;sup&gt;del&lt;/sup&gt; and RUNX1&lt;sup&gt;mut&lt;/sup&gt; patients (40.0% and 44.6%, respectively) had a significantly higher prevalence of MDS with excess blasts 2 (MDS-EB-2) compared to RUNX1&lt;sup&gt;wt&lt;/sup&gt; patients (17.6%, P = 0.01 for RUNX1&lt;sup&gt;del&lt;/sup&gt; vs. RUNX1&lt;sup&gt;wt&lt;/sup&gt;, P &lt; 0.001 for RUNX1&lt;sup&gt;mut&lt;/sup&gt; vs. RUNX1&lt;sup&gt;wt&lt;/sup&gt;). MDS with loss of 5q (MDS 5q-) and MDS with ring sideroblasts (MDS-RS) were underrepresented within &lt;i&gt;RUNX1&lt;/i&gt; aberra","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70452","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785112","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":"Somatic RUNX1 exonic deletions in myelodysplastic syndrome: A rare yet high-risk recurrent genetic aberration","authors":"Ahmed Al-Djaber,&nbsp;Albin Österroos,&nbsp;Alessandro Baldi,&nbsp;Arielle R. Munters,&nbsp;Nikolaj Juul Nitschke,&nbsp;Klas Raaschou-Jensen,&nbsp;Claudia Schöllkopf,&nbsp;Marianne Tang Severinsen,&nbsp;Tatjana Pandzic,&nbsp;Manja Meggendorfer,&nbsp;Joachim Weischenfeldt,&nbsp;Anne Stidsholt Roug,&nbsp;Kirsten Grønbæk,&nbsp;Claes Ladenvall,&nbsp;Torsten Haferlach,&nbsp;Claudia Haferlach,&nbsp;Thale Kristin Olsen,&nbsp;Panagiotis Baliakas","doi":"10.1002/hem3.70452","DOIUrl":"https://doi.org/10.1002/hem3.70452","url":null,"abstract":"&lt;p&gt;Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders characterized by significant genetic and clinical heterogeneity.&lt;span&gt;&lt;sup&gt;1-3&lt;/sup&gt;&lt;/span&gt; Risk stratification and therapeutic decision-making are increasingly guided by the underlying genomic landscape.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; Mutations in the runt-related transcription factor 1 (&lt;i&gt;RUNX1&lt;/i&gt;) gene are observed in 10%–15% of all de novo MDS cases and are among the most well-established prognostic molecular markers in MDS and myeloid neoplasms (MNs).&lt;span&gt;&lt;sup&gt;6-11&lt;/sup&gt;&lt;/span&gt; RUNX1 is a transcription factor essential for normal hematopoiesis, acting as a master regulator of hematopoietic stem cell maintenance, lineage commitment, and megakaryopoiesis.&lt;span&gt;&lt;sup&gt;12, 13&lt;/sup&gt;&lt;/span&gt; Most &lt;i&gt;RUNX1&lt;/i&gt; mutations cause loss-of-function and are associated with specific clinico-biological features.&lt;span&gt;&lt;sup&gt;14&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;We recently reported that somatic &lt;i&gt;RUNX1&lt;/i&gt; exonic deletions (RUNX1&lt;sup&gt;del&lt;/sup&gt;) are recurrent and associated with a poor prognosis in acute myeloid leukemia (AML).&lt;span&gt;&lt;sup&gt;15&lt;/sup&gt;&lt;/span&gt; In addition, the spectrum of reported germline &lt;i&gt;RUNX1&lt;/i&gt; mutations includes a substantial proportion of gross and intragenic exonic deletions, likely underdiagnosed in the past due to technical limitations.&lt;span&gt;&lt;sup&gt;16-18&lt;/sup&gt;&lt;/span&gt; Prompted by these facts, we hypothesized that somatic RUNX1&lt;sup&gt;del&lt;/sup&gt; may be present in MDS.&lt;/p&gt;&lt;p&gt;We analyzed a cohort of 1299 MDS patients using a comprehensive diagnostic approach that included whole-genome sequencing (WGS, &lt;i&gt;n&lt;/i&gt; = 263), array comparative genomic hybridization (CGH, &lt;i&gt;n&lt;/i&gt; = 584), and an in-house next-generation sequencing (NGS) panel (&lt;i&gt;n&lt;/i&gt; = 85) or a combination of the three methods (&lt;i&gt;n&lt;/i&gt; = 367), allowing reliable detection of RUNX1&lt;sup&gt;del&lt;/sup&gt;. Methodological details are described in Supporting Information S1: Supplementary Methods.&lt;/p&gt;&lt;p&gt;Patient characteristics are described in Supporting Information S2: Table 1. Twenty-five (1.9%) patients had &lt;i&gt;RUNX1&lt;/i&gt; deletions (RUNX1&lt;sup&gt;del&lt;/sup&gt;), 121 (9.3%) had &lt;i&gt;RUNX1&lt;/i&gt; mutations (RUNX1&lt;sup&gt;mut&lt;/sup&gt;), and 1153 (88.8%) had no &lt;i&gt;RUNX1&lt;/i&gt; aberration (RUNX1&lt;sup&gt;wt&lt;/sup&gt;). Three of the RUNX1&lt;sup&gt;mut&lt;/sup&gt; patients also had a concurrent &lt;i&gt;RUNX1&lt;/i&gt; deletion. The final cohort had a median age of 73 years (range 23–94 years) with 756 (58.2%) men.&lt;/p&gt;&lt;p&gt;Diagnostic categorization by WHO 2017&lt;span&gt;&lt;sup&gt;19&lt;/sup&gt;&lt;/span&gt; was available for 1242 (95.6%) patients (Supporting Information S2: Table 1). RUNX1&lt;sup&gt;del&lt;/sup&gt; and RUNX1&lt;sup&gt;mut&lt;/sup&gt; patients (40.0% and 44.6%, respectively) had a significantly higher prevalence of MDS with excess blasts 2 (MDS-EB-2) compared to RUNX1&lt;sup&gt;wt&lt;/sup&gt; patients (17.6%, P = 0.01 for RUNX1&lt;sup&gt;del&lt;/sup&gt; vs. RUNX1&lt;sup&gt;wt&lt;/sup&gt;, P &lt; 0.001 for RUNX1&lt;sup&gt;mut&lt;/sup&gt; vs. RUNX1&lt;sup&gt;wt&lt;/sup&gt;). MDS with loss of 5q (MDS 5q-) and MDS with ring sideroblasts (MDS-RS) were underrepresented within &lt;i&gt;RUNX1&lt;/i&gt; aberra","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70452","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783483","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 polygenic etiology for inherited thrombocytopenias of unknown origin","authors":"Federica Isidori,&nbsp;Federica Melazzini,&nbsp;Federica Santonastaso,&nbsp;Caterina Marconi,&nbsp;Valeria Bozzi,&nbsp;Serena Barozzi,&nbsp;Alessandro Mattiaccio,&nbsp;Tania Giangregorio,&nbsp;Emanuela Iovino,&nbsp;Giuseppe Palumbo,&nbsp;Carlo Sidore,&nbsp;Nicola Pirastu,&nbsp;Alessandro Gialluisi,&nbsp;Simona Costanzo,&nbsp;Licia Iacoviello,&nbsp;Nicole Soranzo,&nbsp;Marco Seri,&nbsp;Alessandro Pecci,&nbsp;Tommaso Pippucci","doi":"10.1002/hem3.70459","DOIUrl":"https://doi.org/10.1002/hem3.70459","url":null,"abstract":"&lt;p&gt;Inherited thrombocytopenias (ITs) are a complex of rare diseases characterized by a congenital reduction in platelet count (PC). Advancements in genomic sequencing across the last two decades revolutionized the molecular diagnosis of these conditions: to date, ITs are recognized as a genetically heterogeneous group of monogenic disorders linked to rare disruptive variants distributed over more than 45 well-curated genes.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Despite this progress, 30% to 50% of patients remain without a molecular diagnosis even after extensive investigations integrating next-generation sequencing (NGS) techniques with phenotypic characterization (ITs of unknown origin).&lt;span&gt;&lt;sup&gt;3-5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;At the population level, genome-wide association studies (GWAS) highlighted many common single-nucleotide variants (SNVs) associated with quantitative blood traits, among which PC stands out for its high heritability (54%–87%),&lt;span&gt;&lt;sup&gt;6-8&lt;/sup&gt;&lt;/span&gt; with common variants explaining ~30% of its variability (UKB SNP-Heritability Browser).&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Polygenic risk scores (PRSs) recently emerged as an effective strategy to combine the influence of multiple common SNVs, with individually weak effects, into a single measure of genetic risk. The observation that, for several common diseases, extreme PRSs confer a risk comparable to rare monogenic mutations led to their introduction as emerging tools in diagnostics.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Challenging the pure monogenic paradigm, we hypothesized that at least a proportion of cases of IT of unknown origin are explained by the combined effect of multiple common SNVs negatively associated with PC in the population, resulting in a high-risk PRS, mimicking the presence of a rare mutation. We therefore searched for an association between high-risk PRS for PC (PC-PRS) and a clinical diagnosis of IT in those patients orphan of a monogenic cause.&lt;/p&gt;&lt;p&gt;To identify and validate the best-performing PC-PRS model, the obtained lists of SNVs for each of the two parallel approaches were then used to calculate weights in the Moli-sani cohort (Figure 1C). To enable comparisons of PRS distributions between the IT cohort and the Moli-sani controls, we used Student's &lt;i&gt;t&lt;/i&gt;-test to identify the best-performing model of the two and validate it on the Epi25 cohort (Supporting Information Materials).&lt;/p&gt;&lt;p&gt;The two optimal PC-PRS models, derived from Moli-sani and the meta-analysis,&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt; respectively, identified 9531 SNVs (corresponding to an in-house training P threshold &lt;0.16) and 48 SNVs.&lt;/p&gt;&lt;p&gt;Using either model, IT cases showed significantly lower mean PC-PRS than Moli-sani controls, with PRS-48 (P = 5.9 × 10&lt;sup&gt;−4&lt;/sup&gt;; Figure 1C, right panel) outperforming PRS-9531 (P = 0.02; Figure 1C, left panel).&lt;/p&gt;&lt;p&gt;We independently validated PRS-48 by comparing the IT and Epi25 cohorts (P = 8.99 × 10&lt;sup&gt;−5&lt;/sup&gt;; Figure 2A). Stratifying subjects against the deci","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785113","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":"Sinusoidal obstruction syndrome in children with B-acute lymphoblastic leukemia (B-ALL) treated with inotuzumab ozogamicin: Results from the ITCC-059 trial","authors":"Angela Iannicelli,&nbsp;Franco Locatelli,&nbsp;Yilin Jiang,&nbsp;Anneke Ammerlaan,&nbsp;Susana Rives,&nbsp;Inge M. van der Sluis,&nbsp;Caroline Lindemans,&nbsp;Bella Bielorai,&nbsp;Cristina Díaz de Heredia,&nbsp;Andrej Lissat,&nbsp;Claudia Rossig,&nbsp;Arnaud Petit,&nbsp;Fanny Rialland Battisti,&nbsp;Carmelo Rizzari,&nbsp;Anna B. Nilsson,&nbsp;Benedicte Bruno,&nbsp;Alba Rubio San Simón,&nbsp;Lucie Sramkova,&nbsp;Gernot Engstler,&nbsp;Uta Dirksen,&nbsp;Benoit Brethon,&nbsp;Barbara De Moerloose,&nbsp;Marlène Pasquet,&nbsp;Peter McCarthy,&nbsp;Karsten Nysom,&nbsp;Carine Halfon-Domenech,&nbsp;Nicoletta Bertorello,&nbsp;Jochen Buechner,&nbsp;Peter Bader,&nbsp;C. Michel Zwaan,&nbsp;Erica Brivio","doi":"10.1002/hem3.70448","DOIUrl":"https://doi.org/10.1002/hem3.70448","url":null,"abstract":"&lt;p&gt;Inotuzumab ozogamicin (InO) is a CD22-directed antibody–drug conjugate linked to calicheamicin with substantial antileukemic activity in pediatric relapsed or refractory (R/R) B-acute lymphoblastic leukemia (B-ALL) and is widely used as reinduction/bridging therapy to hematopoietic stem cell transplantation (HSCT).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Despite its efficacy, sinusoidal obstruction syndrome (SOS) remains a relevant safety concern, particularly in the post-HSCT setting.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Different mechanisms have been proposed for InO-associated hepatotoxicity.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Although CD22 is not expressed on normal hepatocytes, malignant CD22-positive blasts may infiltrate hepatic sinusoids, resulting in local release of calicheamicin and subsequent endothelial injury. Off-target uptake of InO by liver sinusoidal endothelial cells via Fcγ receptor-mediated endocytosis may cause intracellular accumulation of calicheamicin, suggesting direct toxicity, as also described for gemtuzumab ozogamicin.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; In addition, CD22 expression may extend beyond B cells to tissue-resident macrophages, including liver-resident Kupffer cells, contributing to local cytotoxicity.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; These mechanisms converge on sinusoidal endothelial damage, a hallmark also observed after HSCT conditioning, which may explain increased SOS risk when InO is administered prior to HSCT.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;ITCC-059 is an international Phase I–II trial evaluating the safety and activity of InO as a single agent or in combination with chemotherapy in pediatric R/R B-ALL.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Based on the ITCC-059 trial, InO received pediatric regulatory approval for patients aged ≥ 1 year with R/R CD22-positive B-ALL.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;In this study, we assessed the incidence, clinical outcomes, and risk factors of SOS in 120 pediatric patients treated with InO in the ITCC-059 trial. Study design, eligibility criteria, and baseline characteristics are detailed in the Supplementary Text and Supporting Information S1: Tables 1–3.&lt;/p&gt;&lt;p&gt;SOS was observed in 18/120 patients (15%), including 4 cases not associated with HSCT (Supporting Information S1: Figure 1), occurring during the first cycle of single-agent InO (&lt;i&gt;n&lt;/i&gt; = 2) or after subsequent chemotherapy administered due to non-response (&lt;i&gt;n&lt;/i&gt; = 2). The remaining 14 SOS cases were diagnosed after HSCT (&lt;i&gt;n&lt;/i&gt; = 68). All post-HSCT SOS cases occurred in patients transplanted within 6 months of the last InO dose.&lt;/p&gt;&lt;p&gt;Overall, 13 of the 18 patients (72%) who developed SOS achieved complete resolution, while 5 (28%) deceased with unresolved SOS. Among post-HSCT cases, 11 of 14 recovered, whereas 3 deceased from complications associated with SOS (septic shock &lt;i&gt;n&lt;/i&gt; = 1 and multi-organ failure &lt;i&gt;n&lt;/i&gt; = 2). Despite initial recovery, five of these patients deceased due to transplant-related complications or relapse.&lt;/p&gt;&lt;p&gt;To explore risk fa","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785119","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 polygenic etiology for inherited thrombocytopenias of unknown origin","authors":"Federica Isidori,&nbsp;Federica Melazzini,&nbsp;Federica Santonastaso,&nbsp;Caterina Marconi,&nbsp;Valeria Bozzi,&nbsp;Serena Barozzi,&nbsp;Alessandro Mattiaccio,&nbsp;Tania Giangregorio,&nbsp;Emanuela Iovino,&nbsp;Giuseppe Palumbo,&nbsp;Carlo Sidore,&nbsp;Nicola Pirastu,&nbsp;Alessandro Gialluisi,&nbsp;Simona Costanzo,&nbsp;Licia Iacoviello,&nbsp;Nicole Soranzo,&nbsp;Marco Seri,&nbsp;Alessandro Pecci,&nbsp;Tommaso Pippucci","doi":"10.1002/hem3.70459","DOIUrl":"https://doi.org/10.1002/hem3.70459","url":null,"abstract":"&lt;p&gt;Inherited thrombocytopenias (ITs) are a complex of rare diseases characterized by a congenital reduction in platelet count (PC). Advancements in genomic sequencing across the last two decades revolutionized the molecular diagnosis of these conditions: to date, ITs are recognized as a genetically heterogeneous group of monogenic disorders linked to rare disruptive variants distributed over more than 45 well-curated genes.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Despite this progress, 30% to 50% of patients remain without a molecular diagnosis even after extensive investigations integrating next-generation sequencing (NGS) techniques with phenotypic characterization (ITs of unknown origin).&lt;span&gt;&lt;sup&gt;3-5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;At the population level, genome-wide association studies (GWAS) highlighted many common single-nucleotide variants (SNVs) associated with quantitative blood traits, among which PC stands out for its high heritability (54%–87%),&lt;span&gt;&lt;sup&gt;6-8&lt;/sup&gt;&lt;/span&gt; with common variants explaining ~30% of its variability (UKB SNP-Heritability Browser).&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Polygenic risk scores (PRSs) recently emerged as an effective strategy to combine the influence of multiple common SNVs, with individually weak effects, into a single measure of genetic risk. The observation that, for several common diseases, extreme PRSs confer a risk comparable to rare monogenic mutations led to their introduction as emerging tools in diagnostics.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Challenging the pure monogenic paradigm, we hypothesized that at least a proportion of cases of IT of unknown origin are explained by the combined effect of multiple common SNVs negatively associated with PC in the population, resulting in a high-risk PRS, mimicking the presence of a rare mutation. We therefore searched for an association between high-risk PRS for PC (PC-PRS) and a clinical diagnosis of IT in those patients orphan of a monogenic cause.&lt;/p&gt;&lt;p&gt;To identify and validate the best-performing PC-PRS model, the obtained lists of SNVs for each of the two parallel approaches were then used to calculate weights in the Moli-sani cohort (Figure 1C). To enable comparisons of PRS distributions between the IT cohort and the Moli-sani controls, we used Student's &lt;i&gt;t&lt;/i&gt;-test to identify the best-performing model of the two and validate it on the Epi25 cohort (Supporting Information Materials).&lt;/p&gt;&lt;p&gt;The two optimal PC-PRS models, derived from Moli-sani and the meta-analysis,&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt; respectively, identified 9531 SNVs (corresponding to an in-house training P threshold &lt;0.16) and 48 SNVs.&lt;/p&gt;&lt;p&gt;Using either model, IT cases showed significantly lower mean PC-PRS than Moli-sani controls, with PRS-48 (P = 5.9 × 10&lt;sup&gt;−4&lt;/sup&gt;; Figure 1C, right panel) outperforming PRS-9531 (P = 0.02; Figure 1C, left panel).&lt;/p&gt;&lt;p&gt;We independently validated PRS-48 by comparing the IT and Epi25 cohorts (P = 8.99 × 10&lt;sup&gt;−5&lt;/sup&gt;; Figure 2A). Stratifying subjects against the deci","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785176","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":"Sinusoidal obstruction syndrome in children with B-acute lymphoblastic leukemia (B-ALL) treated with inotuzumab ozogamicin: Results from the ITCC-059 trial","authors":"Angela Iannicelli,&nbsp;Franco Locatelli,&nbsp;Yilin Jiang,&nbsp;Anneke Ammerlaan,&nbsp;Susana Rives,&nbsp;Inge M. van der Sluis,&nbsp;Caroline Lindemans,&nbsp;Bella Bielorai,&nbsp;Cristina Díaz de Heredia,&nbsp;Andrej Lissat,&nbsp;Claudia Rossig,&nbsp;Arnaud Petit,&nbsp;Fanny Rialland Battisti,&nbsp;Carmelo Rizzari,&nbsp;Anna B. Nilsson,&nbsp;Benedicte Bruno,&nbsp;Alba Rubio San Simón,&nbsp;Lucie Sramkova,&nbsp;Gernot Engstler,&nbsp;Uta Dirksen,&nbsp;Benoit Brethon,&nbsp;Barbara De Moerloose,&nbsp;Marlène Pasquet,&nbsp;Peter McCarthy,&nbsp;Karsten Nysom,&nbsp;Carine Halfon-Domenech,&nbsp;Nicoletta Bertorello,&nbsp;Jochen Buechner,&nbsp;Peter Bader,&nbsp;C. Michel Zwaan,&nbsp;Erica Brivio","doi":"10.1002/hem3.70448","DOIUrl":"https://doi.org/10.1002/hem3.70448","url":null,"abstract":"&lt;p&gt;Inotuzumab ozogamicin (InO) is a CD22-directed antibody–drug conjugate linked to calicheamicin with substantial antileukemic activity in pediatric relapsed or refractory (R/R) B-acute lymphoblastic leukemia (B-ALL) and is widely used as reinduction/bridging therapy to hematopoietic stem cell transplantation (HSCT).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Despite its efficacy, sinusoidal obstruction syndrome (SOS) remains a relevant safety concern, particularly in the post-HSCT setting.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Different mechanisms have been proposed for InO-associated hepatotoxicity.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Although CD22 is not expressed on normal hepatocytes, malignant CD22-positive blasts may infiltrate hepatic sinusoids, resulting in local release of calicheamicin and subsequent endothelial injury. Off-target uptake of InO by liver sinusoidal endothelial cells via Fcγ receptor-mediated endocytosis may cause intracellular accumulation of calicheamicin, suggesting direct toxicity, as also described for gemtuzumab ozogamicin.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; In addition, CD22 expression may extend beyond B cells to tissue-resident macrophages, including liver-resident Kupffer cells, contributing to local cytotoxicity.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; These mechanisms converge on sinusoidal endothelial damage, a hallmark also observed after HSCT conditioning, which may explain increased SOS risk when InO is administered prior to HSCT.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;ITCC-059 is an international Phase I–II trial evaluating the safety and activity of InO as a single agent or in combination with chemotherapy in pediatric R/R B-ALL.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Based on the ITCC-059 trial, InO received pediatric regulatory approval for patients aged ≥ 1 year with R/R CD22-positive B-ALL.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;In this study, we assessed the incidence, clinical outcomes, and risk factors of SOS in 120 pediatric patients treated with InO in the ITCC-059 trial. Study design, eligibility criteria, and baseline characteristics are detailed in the Supplementary Text and Supporting Information S1: Tables 1–3.&lt;/p&gt;&lt;p&gt;SOS was observed in 18/120 patients (15%), including 4 cases not associated with HSCT (Supporting Information S1: Figure 1), occurring during the first cycle of single-agent InO (&lt;i&gt;n&lt;/i&gt; = 2) or after subsequent chemotherapy administered due to non-response (&lt;i&gt;n&lt;/i&gt; = 2). The remaining 14 SOS cases were diagnosed after HSCT (&lt;i&gt;n&lt;/i&gt; = 68). All post-HSCT SOS cases occurred in patients transplanted within 6 months of the last InO dose.&lt;/p&gt;&lt;p&gt;Overall, 13 of the 18 patients (72%) who developed SOS achieved complete resolution, while 5 (28%) deceased with unresolved SOS. Among post-HSCT cases, 11 of 14 recovered, whereas 3 deceased from complications associated with SOS (septic shock &lt;i&gt;n&lt;/i&gt; = 1 and multi-organ failure &lt;i&gt;n&lt;/i&gt; = 2). Despite initial recovery, five of these patients deceased due to transplant-related complications or relapse.&lt;/p&gt;&lt;p&gt;To explore risk fa","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785074","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":"Autologous stem cell transplantation versus consolidation chemotherapy as postremission treatment in newly diagnosed favorable- and intermediate-risk patients with AML: A comparative analysis of HOVON–SAKK–Nordic trials","authors":"Dimitrios Kotsos,&nbsp;Carin Hazenberg,&nbsp;Thomas Pabst,&nbsp;Patrycja Gradowska,&nbsp;Markus G. Manz,&nbsp;Johan Maertens,&nbsp;Carlos Graux,&nbsp;Marie-Christiane Vekemans,&nbsp;Bjorn T. Gjertsen,&nbsp;Sören Lehmann,&nbsp;Catharina H. M. J. Van Elssen,&nbsp;Peter J. M. Valk,&nbsp;Edo Vellenga,&nbsp;Gert Ossenkoppele,&nbsp;Bob Löwenberg,&nbsp;Marc H. G. P. Raaijmakers,&nbsp;Gerwin Huls,&nbsp;Jurjen Versluis","doi":"10.1002/hem3.70462","DOIUrl":"https://doi.org/10.1002/hem3.70462","url":null,"abstract":"<p>High-dose chemotherapy (CT), followed by autologous hematopoietic cell transplantation (auto-HCT) or consolidation CT, are postremission strategies for European LeukemiaNet 2022 (ELN2022) favorable- or intermediate-risk patients with acute myeloid leukemia (AML) in complete remission (CR) without measurable residual disease (MRD). We conducted a retrospective, nonrandomized analysis to compare the efficacy and safety of auto-HCT versus CT in newly diagnosed AML patients aged 18–65 years treated within two recent HOVON–SAKK–Nordic trials. From a total of 1005 patients with ELN2022 favorable- or intermediate-risk AML, 224 received busulfan/cyclophosphamide (Bu/Cy), followed by auto-HCT, and 199 received mitoxantrone/etoposide-based CT. The 5-year relapse-free survival (RFS) and overall survival (OS) were comparable between auto-HCT and CT (RFS: 60% vs. 56%, P = 0.70; OS: 72% vs. 71%, P = 0.76). In multivariable analysis, auto-HCT was not associated with a significant difference in RFS (HR 0.80, 95% CI 0.56–1.13, P = 0.20) or OS (HR 0.91, 95% CI 0.60–1.37, P = 0.64). Median time to platelet and neutrophil recovery was shorter with auto-HCT than CT (platelet: 42 vs. 57 days, neutrophil: 13 vs. 39 days). Subgroup analysis revealed that patients achieving CR after the second induction cycle or with baseline white blood cell counts &gt;20 × 10⁹/L had longer RFS with auto-HCT compared to CT (HR 0.17, P = 0.003 and HR 0.48, P = 0.02), which was not observed for OS. Focusing on ELN2022 favorable-risk patients (excluding <i>NPM1</i>mut MRD-positive) and MRD-negative intermediate-risk patients, RFS and OS were not different between consolidation strategies. Collectively, auto-HCT yielded similar RFS and OS to mitoxantrone/etoposide-based CT in favorable- and intermediate-risk AML, particularly in MRD-negative patients, with faster hematologic recovery.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 8","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785073","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}