HemaSphere最新文献

筛选
英文 中文
Quality of vitamin K antagonist treatment during the last year of life 生命最后一年维生素K拮抗剂治疗的质量
IF 7.6 2区 医学
HemaSphere Pub Date : 2025-05-19 DOI: 10.1002/hem3.70135
Chantal Visser, Eva K. Kempers, Jamilla Goedgebuur, Denise Abbel, Sarah J. Aldridge, Adrian Edwards, Michelle Edwards, Geert-Jan Geersing, Anne Gulbech Ording, Sjef J. C. M. van de Leur, Kate J. Lifford, Isabelle Mahé, Simon P. Mooijaart, Melchior C. Nierman, Johanneke E. A. Portielje, Mette Søgaard, Sebastian Szmit, Nynke M. Wiersma, Simon I. R. Noble, Frederikus A. Klok, Qingui Chen, Suzanne C. Cannegieter, Eric C. T. Geijteman, Marieke J. H. A. Kruip, SERENITY Consortium
{"title":"Quality of vitamin K antagonist treatment during the last year of life","authors":"Chantal Visser,&nbsp;Eva K. Kempers,&nbsp;Jamilla Goedgebuur,&nbsp;Denise Abbel,&nbsp;Sarah J. Aldridge,&nbsp;Adrian Edwards,&nbsp;Michelle Edwards,&nbsp;Geert-Jan Geersing,&nbsp;Anne Gulbech Ording,&nbsp;Sjef J. C. M. van de Leur,&nbsp;Kate J. Lifford,&nbsp;Isabelle Mahé,&nbsp;Simon P. Mooijaart,&nbsp;Melchior C. Nierman,&nbsp;Johanneke E. A. Portielje,&nbsp;Mette Søgaard,&nbsp;Sebastian Szmit,&nbsp;Nynke M. Wiersma,&nbsp;Simon I. R. Noble,&nbsp;Frederikus A. Klok,&nbsp;Qingui Chen,&nbsp;Suzanne C. Cannegieter,&nbsp;Eric C. T. Geijteman,&nbsp;Marieke J. H. A. Kruip,&nbsp;SERENITY Consortium","doi":"10.1002/hem3.70135","DOIUrl":"https://doi.org/10.1002/hem3.70135","url":null,"abstract":"<p>Limited data exist on the quality of anticoagulation in patients approaching the end of life. This study evaluated vitamin K antagonist (VKA) anticoagulation control during the last year of life, using nationwide data from Statistics Netherlands, linked to anticoagulation clinics' data and the Netherlands Cancer Registry. We included prevalent VKA users who were hospitalized with a severe medical condition and died between January 1, 2013, and December 31, 2019. Anticoagulation control was assessed using time in therapeutic range (TTR), time above therapeutic range (TAR), and time below therapeutic range (TBR) and the international normalized ratio (INR) variance growth rate (VGR), which reflects INR variability. Anticoagulation control was examined by two approaches: (1) over four intervals (0–12 months, 0–9 months, 0–6 months, and 0–3 months preceding death), and (2) in 3-month intervals (9–12, 6–9, 3–6, and 0–3 months before death) to describe temporal changes. Among 6874 VKA users in their last year of life (median age 82 [Interquartile range: 76–87] years, 46.9% female), the most prevalent severe medical conditions were heart disease (60.4%), cancer (16.2%), and hip fracture (15.2%). As death approached, TTR and TBR decreased, while TAR and mean VGR increased, particularly in the last 3 months of life. This decline was more pronounced in cancer patients and acenocoumarol users. In conclusion, the quality of VKA anticoagulation declined in the last year of life in severely ill patients, marked by reduced TTR and increased TAR and VGR, suggesting an increased bleeding risk. These findings highlight the importance of reassessing VKA use and considering discontinuation in patients approaching the end of life.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085259","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}
引用次数: 0
Mutational signatures and kataegis in pediatric B-cell precursor acute lymphoblastic leukemia 儿童b细胞前体急性淋巴细胞白血病的突变特征和kataegis
IF 7.6 2区 医学
HemaSphere Pub Date : 2025-05-19 DOI: 10.1002/hem3.70136
Rebeqa Gunnarsson, Minjun Yang, Andrea Biloglav, Kristina B. Lundin-Ström, Henrik Lilljebjörn, Anders Castor, Thoas Fioretos, Linda Olsson-Arvidsson, Kajsa Paulsson, Bertil Johansson
{"title":"Mutational signatures and kataegis in pediatric B-cell precursor acute lymphoblastic leukemia","authors":"Rebeqa Gunnarsson,&nbsp;Minjun Yang,&nbsp;Andrea Biloglav,&nbsp;Kristina B. Lundin-Ström,&nbsp;Henrik Lilljebjörn,&nbsp;Anders Castor,&nbsp;Thoas Fioretos,&nbsp;Linda Olsson-Arvidsson,&nbsp;Kajsa Paulsson,&nbsp;Bertil Johansson","doi":"10.1002/hem3.70136","DOIUrl":"https://doi.org/10.1002/hem3.70136","url":null,"abstract":"&lt;p&gt;Mutational single base substitution (SBS) and insertion/deletion (indel; ID) signatures are characteristic patterns of somatic mutations in cancer that may reflect underlying etiologic factors or pathogenetic mechanisms,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; for example, deamination of 5-methylcytosine to thymine (SBS1), activity of the APOBEC family of cytidine deaminases (SBS2, SBS13), DNA damage caused by reactive oxygen species (ROS; SBS18), and defects of DNA replication and repair (ID1) (https://cancer.sanger.ac.uk/cosmic/signatures). In recent years, sequencing studies of B-cell precursor acute lymphoblastic leukemias (BCP ALL) have identified SBS signatures of etiological/pathogenetic importance.&lt;span&gt;&lt;sup&gt;2-8&lt;/sup&gt;&lt;/span&gt; However, much remains to be ascertained, such as ID signatures and differences in signatures between major and minor clones.&lt;/p&gt;&lt;p&gt;We performed whole genome sequencing (WGS) of 84 pediatric BCP ALLs with high hyperdiploidy (HeH; &lt;i&gt;n&lt;/i&gt; = 23), &lt;i&gt;ETV6&lt;/i&gt;::&lt;i&gt;RUNX1&lt;/i&gt; (&lt;i&gt;n&lt;/i&gt; = 23), &lt;i&gt;TCF3&lt;/i&gt;::&lt;i&gt;PBX1&lt;/i&gt; (&lt;i&gt;n&lt;/i&gt; = 9), and B-other (&lt;i&gt;n&lt;/i&gt; = 29) to identify SBS/ID signatures and to explore differences between major clones and minor subclones. In addition, WGS and RNA-seq were used to detect fusion genes, single gene rearrangements, single-nucleotide variants (SNVs), indels, expression patterns of gene fusions and gene mutations, and kataegic regions (i.e., localized hypermutations defined by a minimum of at least six mutations with an intermutation distance of ≤1000 bp)&lt;span&gt;&lt;sup&gt;9, 10&lt;/sup&gt;&lt;/span&gt; (Supporting Information and Table S1).&lt;/p&gt;&lt;p&gt;The WGS analysis revealed 230 structural variants (SVs; translocations, inversions, and deletions; Table S2): 105 were in-frame fusions (including all &lt;i&gt;ETV6&lt;/i&gt;::&lt;i&gt;RUNX1&lt;/i&gt; and &lt;i&gt;TCF3&lt;/i&gt;::&lt;i&gt;PBX1&lt;/i&gt; fusions; Figure S1), 52 out-of-frame gene fusions, and 73 single gene rearrangements. In total, 44 novel in-frame gene fusions were identified (e.g., three involving &lt;i&gt;PAX5&lt;/i&gt; fused to &lt;i&gt;MECOM&lt;/i&gt;, &lt;i&gt;RBM39&lt;/i&gt;, and &lt;i&gt;STIM2&lt;/i&gt;, respectively) (Figure S2 and Table S3). As expected, all the &lt;i&gt;ETV6&lt;/i&gt;::&lt;i&gt;RUNX1&lt;/i&gt; and &lt;i&gt;TCF3&lt;/i&gt;::&lt;i&gt;PBX1&lt;/i&gt; fusions were expressed; in contrast, only ~50% of the other in-frame fusions were transcribed, as ascertained by RNA-seq (Supporting Information and Table S2). Of the 104,618 SNVs (median 1082/case) and 1987 indels (median 21/case) identified, 791 (0.8%) SNVs and 74 (3.7%) indels occurred in exonic/splice site regions. The numbers of genomic and exonic/splice site SNVs and indels per case were highly correlated (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001; Figure S3), suggesting that the latter SNVs/indels are random and that many of them are “passengers.” In fact, ~30% of the exonic/splice site SNVs were considered benign by SIFT and PolyPhen, only ~20% of them were expressed, and most (77%) genes targeted by exonic/splice site SNVs/indels were non-recurrent (Table S4). Of the 128 recurrently mutated genes, &lt;i&gt;PAX5&lt;/i&gt;, &lt;i&gt;KRAS&lt;/i&gt;, &lt;i&gt;NRAS, IKZF1&lt;/i&gt;, &lt;i&gt;FLT3","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091315","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}
引用次数: 0
Metabolism in hematology: Technological advances open new perspectives on disease biology and treatment 血液学代谢:技术进步为疾病生物学和治疗开辟了新的视角
IF 7.6 2区 医学
HemaSphere Pub Date : 2025-05-19 DOI: 10.1002/hem3.70134
Eileen Haring, Joerg M. Buescher, Petya Apostolova
{"title":"Metabolism in hematology: Technological advances open new perspectives on disease biology and treatment","authors":"Eileen Haring,&nbsp;Joerg M. Buescher,&nbsp;Petya Apostolova","doi":"10.1002/hem3.70134","DOIUrl":"https://doi.org/10.1002/hem3.70134","url":null,"abstract":"<p>The term metabolism refers to the multi-faceted biochemical reactions within a cell or an organism that occur to maintain energy homeostasis, cell growth, and oxidative balance. Cells possess a high metabolic plasticity, allowing them to adapt to the dynamic requirements of their functional state and environment. Deregulated cellular metabolism is a hallmark of many diseases, including benign and malignant hematological conditions. In the last decade, multiple technological innovations in the metabolism field have made in-depth metabolic analysis broadly applicable. Such studies are shedding new light on normal and malignant hematopoiesis and open avenues to a better understanding of the biology of hematological diseases. In this review, we will first give a brief overview of central metabolic processes. Furthermore, we discuss the most commonly used methods to study metabolism. We begin by elaborating on the use of next-generation sequencing to detect metabolism-related genomic mutations and study transcriptional signatures. Furthermore, we discuss methods for measuring protein expression, such as mass spectrometry (MS), flow cytometry, and cytometry time-of-flight. Next, we describe the use of nuclear magnetic resonance spectroscopy, MS, and flow cytometry for metabolite quantification. Finally, we highlight functional assays to probe metabolic pathways in real-time. We illustrate how these technologies and their combination have advanced our understanding of the role of metabolism. Our goal is to provide hematologists with a comprehensive guide to modern techniques in metabolism research, their benefits and disadvantages, and how they guide our understanding of disease and potentially future personalized therapy decisions.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085258","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}
引用次数: 0
Correction to Prevalence of type I Gaucher disease in patients with smoldering or multiple myeloma: Results from the prospective, observational CHAGAL study
IF 7.6 2区 医学
HemaSphere Pub Date : 2025-05-14 DOI: 10.1002/hem3.70142
{"title":"Correction to Prevalence of type I Gaucher disease in patients with smoldering or multiple myeloma: Results from the prospective, observational CHAGAL study","authors":"","doi":"10.1002/hem3.70142","DOIUrl":"https://doi.org/10.1002/hem3.70142","url":null,"abstract":"<p>Morè S, Federici I, Bossi A, et al. Prevalence of type I Gaucher disease in patients with smoldering or multiple myeloma: results from the prospective, observational CHAGAL study. <i>HemaSphere</i>. 2025;9:e70079. https://doi.org/10.1002/hem3.70079</p><p>In the author listing of the manuscript, the name of an author was incorrectly listed as Tommaso C. De Toritto. The correct name is Tommaso Caravita di Toritto.</p><p>Additionally, the author listing requires further amendment due to an error in the initial manuscript draft. As such, Angela Rago is now included as a co-author.</p><p>The original article has been updated. We apologize for this error.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944606","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}
引用次数: 0
Biomarker-adapted treatment in high-risk large B-cell lymphoma 高危大b细胞淋巴瘤的生物标志物适应治疗
IF 7.6 2区 医学
HemaSphere Pub Date : 2025-05-12 DOI: 10.1002/hem3.70139
Sirpa Leppä, Leo Meriranta, Maare Arffman, Judit Jørgensen, Marja-Liisa Karjalainen-Lindsberg, Klaus Beiske, Mette Pedersen, Kristina Drott, Annika Pasanen, Kristiina Karihtala, Susanna Mannisto, Bente Wold, Marianne Brodtkorb, Unn-Merete Fagerli, Thomas Stauffer Larsen, Lars Munksgaard, Kaisa Sunela, Øystein Fluge, Sirkku Jyrkkiö, Peter Brown, Harald Holte
{"title":"Biomarker-adapted treatment in high-risk large B-cell lymphoma","authors":"Sirpa Leppä,&nbsp;Leo Meriranta,&nbsp;Maare Arffman,&nbsp;Judit Jørgensen,&nbsp;Marja-Liisa Karjalainen-Lindsberg,&nbsp;Klaus Beiske,&nbsp;Mette Pedersen,&nbsp;Kristina Drott,&nbsp;Annika Pasanen,&nbsp;Kristiina Karihtala,&nbsp;Susanna Mannisto,&nbsp;Bente Wold,&nbsp;Marianne Brodtkorb,&nbsp;Unn-Merete Fagerli,&nbsp;Thomas Stauffer Larsen,&nbsp;Lars Munksgaard,&nbsp;Kaisa Sunela,&nbsp;Øystein Fluge,&nbsp;Sirkku Jyrkkiö,&nbsp;Peter Brown,&nbsp;Harald Holte","doi":"10.1002/hem3.70139","DOIUrl":"https://doi.org/10.1002/hem3.70139","url":null,"abstract":"<p>Survival rates for patients with high-risk large B-cell lymphoma (LBCL), particularly those with biological risk factors, remain inadequate. We conducted a biomarker-driven phase II trial involving 123 high-risk patients aged 18–64 with LBCL. Based on their biological risk profiles, patients received either R-CHOEP-14 (without risk factors) or DA-EPOCH-R-based regimens (with risk factors). Biological high-risk factors included <i>C-MYC</i> translocation, <i>C-MYC</i> and <i>BCL2</i> co-translocation, <i>17p/TP53</i> deletion, co-expression of MYC and BCL2, and P53 and/or CD5 immunopositivity. Additionally, we evaluated circulating tumor DNA (ctDNA) kinetics during therapy. Sixty-one patients (50%) were classified into biologically high-risk group. Three-year failure-free survival and overall survival rates for the entire study population were 79% and 88%, respectively. DA-EPOCH-R did not improve survival compared to our previous trial, where patients with the same biological risk factor criteria received R-CHOEP-14-based therapy. High pretreatment ctDNA levels, <i>17p/TP53</i> deletion, and <i>TP53</i> mutations were associated with worse outcomes. In contrast, ctDNA negativity at the end of therapy (EOT) was indicative of a cure and effectively addressed false residual PET positivity. The findings demonstrate promising survival for high-risk LBCL patients, aside from those with <i>TP53</i> aberrations, high ctDNA levels, and/or EOT ctDNA positivity.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939163","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}
引用次数: 0
Optimizing therapy for relapsed/refractory classic Hodgkin lymphoma in the era of PD-1 blockade PD-1阻断时代复发/难治性经典霍奇金淋巴瘤的优化治疗
IF 7.6 2区 医学
HemaSphere Pub Date : 2025-05-12 DOI: 10.1002/hem3.70110
Thomas M. Kuczmarski, Ryan C. Lynch
{"title":"Optimizing therapy for relapsed/refractory classic Hodgkin lymphoma in the era of PD-1 blockade","authors":"Thomas M. Kuczmarski,&nbsp;Ryan C. Lynch","doi":"10.1002/hem3.70110","DOIUrl":"https://doi.org/10.1002/hem3.70110","url":null,"abstract":"&lt;p&gt;Most patients with relapsed/refractory (R/R) classic Hodgkin lymphoma (CHL) are cured with primary therapy, but 10%–30% of patients may relapse.&lt;span&gt;&lt;sup&gt;1-3&lt;/sup&gt;&lt;/span&gt; While second-line salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) may cure most R/R patients, the optimal salvage treatment regimen remains undefined. With the advent of targeted therapies, novel agents such as the CD30 antibody-drug conjugate brentuximab vedotin (BV) as well as PD-1 inhibitors such as nivolumab and pembrolizumab have been incorporated into salvage regimens.&lt;span&gt;&lt;sup&gt;4-7&lt;/sup&gt;&lt;/span&gt; Acknowledging the limitations of cross-trial comparison of phase 2 trials, the outcomes with these regimens appear superior to using chemotherapy alone.&lt;span&gt;&lt;sup&gt;8, 9&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;In this issue of &lt;i&gt;HemaSphere&lt;/i&gt;, Mei et al. present the results of their phase 2 trial of combination nivolumab plus ifosfamide, carboplatin, and etoposide (NICE) in patients with high-risk R/R Hodgkin lymphoma.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt; The study was performed in light of an initial PET-adapted approach, in which patients received either nivolumab monotherapy or combination NICE (for patients with residual PET-positive disease after nivolumab lead-in) followed by ASCT.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Given that only 9 of 43 enrolled patients received NICE in the PET-adapted approach, this study was performed to further evaluate the safety and efficacy of NICE before ASCT. In total, 35 patients were enrolled in the study. All patients received one dose of nivolumab monotherapy followed by two cycles of NICE, and seven patients received a third cycle of NICE. Notably, this cohort treated with NICE was restricted to high-risk individuals based on several pre-determined criteria, including relapse within 1 year of completion of first-line therapy or primary refractory disease.&lt;/p&gt;&lt;p&gt;In this study, NICE followed by ASCT demonstrated promising efficacy with a 2-year progression-free survival (PFS) and overall survival (OS) of 88% and 100%, respectively. These efficacy data are comparable to other studies in which a combination of PD-1 inhibitor and chemotherapy was used in the R/R setting.&lt;span&gt;&lt;sup&gt;4, 11&lt;/sup&gt;&lt;/span&gt; Given that the cohort was restricted to patients with high-risk diseases, it makes the efficacy results even more compelling.&lt;/p&gt;&lt;p&gt;While the study demonstrated promising efficacy data, it also determined the regimen to be safe. In fact, toxicities associated with NICE followed by ASCT were similar to if not better than prior studies involving combination chemoimmunotherapy.&lt;span&gt;&lt;sup&gt;4, 6, 11&lt;/sup&gt;&lt;/span&gt; Anemia (69%) and nausea (69%) were the most common toxicities attributed to NICE, while transaminitis (23%), rash (20%), and pruritus (14%) were the most common immune-related adverse events (all grade 1, except for two cases of pruritus that were grade 2). Rates of neutropenia and thrombocytopenia were relatively low at 31% with the maj","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939162","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}
引用次数: 0
Age-stratified machine learning identifies divergent prognostic significance of molecular alterations in AML 年龄分层机器学习识别AML分子改变的不同预后意义
IF 7.6 2区 医学
HemaSphere Pub Date : 2025-05-07 DOI: 10.1002/hem3.70132
Jan-Niklas Eckardt, Waldemar Hahn, Rhonda E. Ries, Szymon D. Chrost, Susann Winter, Sebastian Stasik, Christoph Röllig, Uwe Platzbecker, Carsten Müller-Tidow, Hubert Serve, Claudia D. Baldus, Christoph Schliemann, Kerstin Schäfer-Eckart, Maher Hanoun, Martin Kaufmann, Andreas Burchert, Johannes Schetelig, Martin Bornhäuser, Markus Wolfien, Soheil Meshinchi, Christian Thiede, Jan Moritz Middeke
{"title":"Age-stratified machine learning identifies divergent prognostic significance of molecular alterations in AML","authors":"Jan-Niklas Eckardt,&nbsp;Waldemar Hahn,&nbsp;Rhonda E. Ries,&nbsp;Szymon D. Chrost,&nbsp;Susann Winter,&nbsp;Sebastian Stasik,&nbsp;Christoph Röllig,&nbsp;Uwe Platzbecker,&nbsp;Carsten Müller-Tidow,&nbsp;Hubert Serve,&nbsp;Claudia D. Baldus,&nbsp;Christoph Schliemann,&nbsp;Kerstin Schäfer-Eckart,&nbsp;Maher Hanoun,&nbsp;Martin Kaufmann,&nbsp;Andreas Burchert,&nbsp;Johannes Schetelig,&nbsp;Martin Bornhäuser,&nbsp;Markus Wolfien,&nbsp;Soheil Meshinchi,&nbsp;Christian Thiede,&nbsp;Jan Moritz Middeke","doi":"10.1002/hem3.70132","DOIUrl":"https://doi.org/10.1002/hem3.70132","url":null,"abstract":"<p>Risk stratification in acute myeloid leukemia (AML) is driven by genetics, yet patient age substantially influences therapeutic decisions. To evaluate how age alters the prognostic impact of genetic mutations, we pooled data from 3062 pediatric and adult AML patients from multiple cohorts. Signaling pathway mutations dominated in younger patients, while mutations in epigenetic regulators, spliceosome genes, and <i>TP53</i> alterations became more frequent with increasing age. Machine learning models were trained to identify prognostic variables and predict complete remission and 2-year overall survival, achieving area-under-the-curve scores of 0.801 and 0.791, respectively. Using Shapley (SHAP) values, we quantified the contribution of each variable to model decisions and traced their impact across six age groups: infants, children, adolescents/young adults, adults, seniors, and elderly. The highest contributions to model decisions among genetic variables were found for alterations of <i>NPM1</i>, <i>CEBPA</i>, inv(16), and t(8;21) conferring favorable risk and alterations of <i>TP53, RUNX1, ASXL1</i>, del(5q), -7, and -17 conferring adverse risk, while <i>FLT3</i>-ITD had an ambiguous role conferring favorable treatment responses yet poor overall survival. Age significantly modified the prognostic value of genetic alterations, with no single alteration consistently predicting outcomes across all age groups. Specific alterations associated with aging such as <i>TP53</i>, <i>ASXL1</i>, or del(5q) posed a disproportionately higher risk in younger patients. These results challenge uniform risk stratification models and highlight the need for context-sensitive AML treatment strategies.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914534","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}
引用次数: 0
Integration of gene mutations in risk prognostication for watch-and-wait follicular lymphoma patients initiating first-line treatment 整合基因突变对开始一线治疗的观察等待滤泡性淋巴瘤患者的风险预测
IF 7.6 2区 医学
HemaSphere Pub Date : 2025-05-07 DOI: 10.1002/hem3.70141
Tian-Yuan Xu, Rong-Ji Mu, Hui-Lai Zhang, Bing Xu, Rong Li, Nan Wang, Rui Sun, Rui-Chi Li, Di Fu, Xian-Huo Wang, Zhi-Feng Li, Yan Zhao, Peng-Peng Xu, Shu Cheng, Li Wang, Wei Tang, Zhong Zheng, Wei-Li Zhao
{"title":"Integration of gene mutations in risk prognostication for watch-and-wait follicular lymphoma patients initiating first-line treatment","authors":"Tian-Yuan Xu,&nbsp;Rong-Ji Mu,&nbsp;Hui-Lai Zhang,&nbsp;Bing Xu,&nbsp;Rong Li,&nbsp;Nan Wang,&nbsp;Rui Sun,&nbsp;Rui-Chi Li,&nbsp;Di Fu,&nbsp;Xian-Huo Wang,&nbsp;Zhi-Feng Li,&nbsp;Yan Zhao,&nbsp;Peng-Peng Xu,&nbsp;Shu Cheng,&nbsp;Li Wang,&nbsp;Wei Tang,&nbsp;Zhong Zheng,&nbsp;Wei-Li Zhao","doi":"10.1002/hem3.70141","DOIUrl":"https://doi.org/10.1002/hem3.70141","url":null,"abstract":"<p>Follicular lymphoma (FL) patients with low tumor burden at diagnosis frequently undergo the watch-and-wait (W&amp;W) strategy. The study aimed to facilitate risk assessment in predicting the time to lymphoma treatment (TLT) for W&amp;W patients through an integrated analysis of clinical factors and genetic mutations. A retrospective study was conducted on 214 FL patients managed with W&amp;W between 2016 and 2023. Among them, 184 patients underwent targeted sequencing. The median follow-up was 30.4 months (IQR 21.4–41.9, range 6.4–95.8). A clinico-genetic model m3-PRIMA-PI was developed using the multivariate Cox proportional hazards method, incorporating two clinical parameters (bone marrow involvement and elevated β2-MG) and three gene mutations (<i>KMT2D</i>, <i>EP300</i>, and <i>TP53</i>). Patients were categorized into low (69.0%), intermediate (21.7%), and high (9.2%) risk groups. Probabilities of treatment initiation at one year were 11.0% (95% CI, 5.2%–16.5%), 26.0% (95% CI, 10.7%–38.7%), and 54.3% (95% CI, 22.3%–73.1%); and at 2 years were 29.4% (95% CI, 20.2%–37.5%), 49.8% (95% CI, 31.1%–63.4%), and 93.5% (95% CI, 56.7%–99.0%), respectively. The predictive performance for TLT was superior with m3-PRIMA-PI, achieving a C-index of 0.66 (95% CI, 0.63–0.69), compared to established indexes like FLIPI (C-index 0.59, 95% CI, 0.56–0.62) and FLIPI2 (C-index 0.59, 95% CI, 0.55–0.61). The above results were further validated in an independent external cohort. The m3-PRIMA-PI may provide a promising tool for risk stratification in W&amp;W FL patients.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914535","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}
引用次数: 0
Peripheral T- and natural killer-cell lymphomas: ESMO-EHA Clinical Practice Guideline for diagnosis, treatment, and follow-up 外周T细胞和自然杀伤细胞淋巴瘤:ESMO-EHA临床实践指南的诊断,治疗和随访
IF 7.6 2区 医学
HemaSphere Pub Date : 2025-05-07 DOI: 10.1002/hem3.70128
Francesco d'Amore, Massimo Federico, Laurence de Leval, Fredrik Ellin, Olivier Hermine, Won Seog Kim, François Lemonnier, Joost S. P. Vermaat, Gerald Wulf, Christian Buske, Martin Dreyling, Mats Jerkeman, the ESMO and EHA Guidelines Committees
{"title":"Peripheral T- and natural killer-cell lymphomas: ESMO-EHA Clinical Practice Guideline for diagnosis, treatment, and follow-up","authors":"Francesco d'Amore,&nbsp;Massimo Federico,&nbsp;Laurence de Leval,&nbsp;Fredrik Ellin,&nbsp;Olivier Hermine,&nbsp;Won Seog Kim,&nbsp;François Lemonnier,&nbsp;Joost S. P. Vermaat,&nbsp;Gerald Wulf,&nbsp;Christian Buske,&nbsp;Martin Dreyling,&nbsp;Mats Jerkeman,&nbsp;the ESMO and EHA Guidelines Committees","doi":"10.1002/hem3.70128","DOIUrl":"https://doi.org/10.1002/hem3.70128","url":null,"abstract":"&lt;p&gt;Peripheral T-cell and natural killer (NK)-cell lymphomas (PTCLs) represent a heterogeneous group of neoplasms derived from post-thymic T- or NK cells, with diverse morphological patterns, phenotypes, and clinical presentations. The International Consensus Classification and World Health Organization (WHO) classification of lymphoid and hematopoietic neoplasms recognize &gt;30 PTCL entities&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; (Supporting Information: Table S1 and Supporting Information Section 1). The incidence and epidemiology of PTCL are described in Supporting Information Section 2. This clinical practice guideline (CPG) covers PTCLs with primary nodal, extranodal, and leukemic presentation. Guidelines for primary cutaneous T-cell lymphomas are reported elsewhere.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Accurate identification and diagnosis of PTCL is mandatory for adequate clinical management, as treatment should be adapted for each entity. Several entities present with a wide pathological spectrum and there is substantial overlap in morphology, immunophenotype, and mutational landscape between diseases. The differential diagnosis of PTCL is broad and includes various reactive conditions, particularly primary immune deficiencies, inflammation, autoimmune diseases, infections, Hodgkin lymphoma, and, in some instances, B-cell lymphomas.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Overtly malignant PTCLs must be distinguished from the recently recognized indolent clonal T- or NK-cell lymphoproliferative disorders.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Given the low prevalence of PTCLs, most pathologists have insufficient experience to confidently diagnose them; therefore, diagnosis should be established or confirmed by a hematopathologist with expertise in PTCL who has access to all slides and ≥1 representative paraffin block of the biopsy.&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Clinicopathological correlation is critical for diagnosis, incorporating imaging findings, symptoms, and laboratory information. Anatomical localization can pre-sort for specific entities (e.g., hepatosplenic T-cell lymphoma [HSTCL], Epstein–Barr virus [EBV]-associated extranodal NK- or T-cell lymphoma [ENKTCL] nasal type, enteropathy-associated T-cell lymphoma [EATL], and breast implant-associated anaplastic large-cell lymphoma [BIA-ALCL]). Autoimmune and inflammatory diseases (e.g., celiac disease and inflammatory bowel disease), immunocompromised status, ethnicity, origin from endemic regions (e.g., within Asia, Africa, or South America for adult T-cell leukemia or lymphoma [ATLL]) or infection (e.g., EBV in tumor cells, human T-cell lymphotropic virus type 1 [HTLV-1]) may further support identification of entities.&lt;/p&gt;&lt;p&gt;Diagnosis should rely on surgical excisional or incisional biopsy whenever possible&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; to allow adequate histopathological assessment and provide sufficient tissue for immunohistochemistry (IHC) and molecular studies. When surgery is not possible, core needle biopsy or biopsie","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919542","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}
引用次数: 0
TET3 regulates hematopoietic stem cell homeostasis during embryonic and adult hematopoiesis TET3调节胚胎和成人造血过程中造血干细胞的稳态
IF 7.6 2区 医学
HemaSphere Pub Date : 2025-05-06 DOI: 10.1002/hem3.70140
Harmony C. Ketchum, Claudia Morganti, Chie Yanase, Blake Ebert, Keisuke Ito, Meelad M. Dawlaty
{"title":"TET3 regulates hematopoietic stem cell homeostasis during embryonic and adult hematopoiesis","authors":"Harmony C. Ketchum,&nbsp;Claudia Morganti,&nbsp;Chie Yanase,&nbsp;Blake Ebert,&nbsp;Keisuke Ito,&nbsp;Meelad M. Dawlaty","doi":"10.1002/hem3.70140","DOIUrl":"https://doi.org/10.1002/hem3.70140","url":null,"abstract":"<p>The ten-eleven translocation family of enzymes (TET1/2/3) promotes DNA demethylation and is essential for hematopoiesis. While the roles of TET1 and TET2 are well-studied in hematopoiesis, the requirement of TET3 in embryonic and adult hematopoiesis is less investigated. In this study, by characterizing embryonic and adult hematopoiesis in <i>Tie2</i><sup><i>+/cre</i></sup>; <i>Tet3</i><sup><i>f/f</i></sup> mice, we have established a requirement for TET3 in regulating hematopoietic stem cells (HSCs; CD150<sup>+</sup>CD48<sup>–</sup>). We found that loss of TET3 in the fetal liver and adult bone marrow causes a reduction in the percent of long-term HSCs (LT-HSCs; CD150<sup>+</sup>CD48<sup>–</sup>CD34<sup>–</sup>). This was accompanied by reduced colony forming capacity of TET3-deficient HSCs in vitro and reduced contribution of HSCs after a competitive bone marrow transplantation in vivo. TET3 deficiency increased DNA methylation at several cell cycle regulator genes leading to their down regulation. This is consistent with, and likely underpins, the reduced number of quiescent HSCs in TET3-deficient bone marrow. These findings uncover a new role for TET3 in HSC homeostasis during embryonic and adult hematopoiesis.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909346","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信