Annals of Hematology最新文献

{"title":"AI-based detection of neutrophil dysplasia: an accessible and sensitive model for MDS diagnosis from peripheral blood.","authors":"Nicole H Romano, Christian Ruiz, Pascal Schlaepfer, Stefan Balabanov, Stefan Habringer, Corinne C Widmer","doi":"10.1007/s00277-025-06533-5","DOIUrl":"10.1007/s00277-025-06533-5","url":null,"abstract":"<p><p>Myelodysplastic syndrome / neoplasm (MDS) presents a diagnostic challenge due to the need of expert morphological analysis, and the reliance on genomic analysis of collected bone marrow material for the definite diagnosis. This study aimed to facilitate this process by developing a computer vision AI-based model that is capable of diagnosing MDS from images from peripheral blood smears (PBS). We used a cohort of 43,371 neutrophils from 84 MDS and 60 non-MDS samples to train a neutrophil classifier to differentiate between dysplastic and non-dysplastic cells. The model was initially fed with PBS images from patients with prominent MDS (pMDS) and further refined to detect non-prominent MDS (npMDS), i.e., without clear-cut dysplastic features in their neutrophils. The model learning was only based on the single-cell annotation of the neutrophils from pMDS, without human-generated morphological features as input. The trained neutrophil classifier achieved an overall accuracy of 94%, with a sensitivity and specificity of 0.95 and 0.94, respectively. On a patient-level, the model correctly identified 91 out of the 94 samples, with a sensitivity and specificity of 0.98 and 0.96, respectively, and AUC of 0.999. In npMDS, 43 out of the 44 samples were correctly identified. Our study demonstrates the potential of AI-based models to improve the efficiency of MDS diagnostics. Our model runs on standard CPUs, offering an accessible solution that can be integrated into existing clinical workflows and potentially reduces the dependence on specialized morphologists and genomic analysis from bone marrow punctures.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De-escalated Teclistamab dosing in relapsed/refractory multiple myeloma: Czech myeloma group real-world evidence analysis","authors":"Martin Stork,&nbsp;Jakub Radocha,&nbsp;Jana Mihalyova,&nbsp;Ivan Spicka,&nbsp;Tomas Pika,&nbsp;Alexandra Jungova,&nbsp;Ivanna Boichuk,&nbsp;Klara Mensikova,&nbsp;Jan Straub,&nbsp;Frantisek Sedlak,&nbsp;Jiri Minarik,&nbsp;Petra Krhovska,&nbsp;Denisa Novakova,&nbsp;Michaela Hornakova,&nbsp;Zdenka Knechtova,&nbsp;Nela Sendlerova,&nbsp;Tereza Dekojova,&nbsp;Vladimir Maisnar,&nbsp;Tomas Jelinek,&nbsp;Roman Hajek,&nbsp;Ludek Pour","doi":"10.1007/s00277-025-06529-1","DOIUrl":"10.1007/s00277-025-06529-1","url":null,"abstract":"<div><p>Teclistamab, a BCMA×CD3 bispecific antibody, demonstrates high efficacy in relapsed/refractory multiple myeloma (RRMM). However, optimal dosing strategies outside clinical trials remain undefined. Thus, we performed a retrospective, multicentre analysis of 73 RRMM patients treated with teclistamab monotherapy at Czech Myeloma Group centres between 2023 and 2025. The study compared efficacy and safety between patients receiving standard weekly dosing and those with reduced-frequency dosing. The whole cohort had a median age of 67 years; 68.5% were penta-refractory. Dosing was de-escalated in 24.7% of patients, typically within one month of treatment initiation. Median progression-free survival (PFS) was 9.41 months and was comparable between weekly and non-weekly groups (9.1 vs. 11.3 months; <i>p</i> = 0.141), despite a significantly lower relative dose intensity in the latter (60.5% vs. 87.0%; <i>p</i> &lt; 0.001). Infection rates and severe adverse events were similar between groups. A lower incidence of neutropenia was observed with less frequent dosing, but this did not translate into reduced infection burden. In conclusion, in real-world practice, early de-escalation of teclistamab dosing appears to maintain clinical efficacy. These findings support ongoing efforts to individualize treatment schedules with the aim of balancing effectiveness, tolerability, and patient-specific factors in BCMA-targeted therapy.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 8","pages":"4141 - 4147"},"PeriodicalIF":2.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06529-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond transfusions and transplants: genomic innovations rewriting the narrative of thalassemia","authors":"Liangbin Shi,&nbsp;Xili Yan,&nbsp;Yanwei Xia,&nbsp;Yingdi Zhao,&nbsp;Xiuling Zhu,&nbsp;Qiang Li,&nbsp;Zhiliang Xu","doi":"10.1007/s00277-025-06548-y","DOIUrl":"10.1007/s00277-025-06548-y","url":null,"abstract":"<div><p>Thalassemia is a globally prevalent inherited blood disorder that usually leads to severe complications and even premature death due to impaired hemoglobin synthesis. The conventional treatment approach encompasses a range of interventions, including red blood cell transfusions, iron chelation therapy, splenectomy, and allogeneic hematopoietic stem cell transplantation. However, transfusion-induced iron overload and the limitation of graft matching have emerged as significant clinical impediments. In recent years, with the advent of precision medicine and translational research, the treatment of thalassemia has undergone a paradigm shift toward stem cell gene therapy, gene editing combined with nanodelivery, and pharmacogenomics-guided, personalized treatment regimens. In preclinical and early-phase clinical trials, these approaches have demonstrated efficacy in modulating hemoglobin gene expression and reversing ineffective hematopoiesis. Consequently, this review explores the constraints imposed by conventional therapeutic approaches and the advancements in the field of gene therapy for thalassaemia. It elucidates the mechanisms of gene editing and the potential of stem cell therapies. Furthermore, the discourse encompasses the advancement of primary prevention strategies, including genetic testing and prenatal screening, in the context of reducing morbidity. It is our hope that this review will provide the latest clues and insights in gene therapy for the effective management of thalassemia.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 8","pages":"3963 - 3980"},"PeriodicalIF":2.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06548-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the current situation and influencing factors of home treatment for children with hemophilia in China","authors":"Chunli Wang,&nbsp;Runhui Wu,&nbsp;Xumei Wang,&nbsp;Wei Chi,&nbsp;Xinyi Wu,&nbsp;Guoqing Liu","doi":"10.1007/s00277-025-06552-2","DOIUrl":"10.1007/s00277-025-06552-2","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the current status of home treatment for children with hemophilia in China and identify key influencing factors.</p><h3>Methods</h3><p>Based on a comprehensive literature review and expert consultation, the <i>Questionnaire on Home Treatment for Children with Hemophilia</i> was developed. The study targeted fathers or mothers of children with hemophilia who were registered on the official website of “Home for Hemophilia Patients.” From June 1, 2022, to July 1, 2023, a questionnaire survey was conducted through centralized dissemination via short message service.</p><h3>Results</h3><p>A total of 293 valid responses were collected. Among them, 118 children (40.3%) had initiated self-injection at home. Multivariate logistic regression analysis identified several significant factors associated with home treatment implementation, including child’s age, ethnicity, hemophilia subtype, assistance from medically trained relatives or friends, use of emicizumab, operator confidence in venipuncture, prior self-injection training, understanding of aseptic techniques, and availability of syringes and bandages.</p><h3>Conclusion</h3><p>The implementation of home treatment for children with hemophilia requires further improvement. Particular attention should be given to younger patients. In addition, it is essential to enhance self-injection training, boost caregivers’ confidence in performing venipuncture, and improve the availability of disposable sterile supplies.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 8","pages":"4037 - 4044"},"PeriodicalIF":2.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06552-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic modifiers of frequent vaso-occlusive hospitalizations among individuals with sickle cell disease (SCD)","authors":"Mina Cintho Ozahata,&nbsp;Isabel Gomes,&nbsp;Beatriz A. Oliveira,&nbsp;Miriam Park,&nbsp;Daniela O. W. Rodrigues,&nbsp;Anna Bárbara Carneiro-Proietti,&nbsp;Cláudia Máximo,&nbsp;Allison Ashley-Koch,&nbsp;Marilyn Telen,&nbsp;Shannon Kelly,&nbsp;Brian Custer,&nbsp;Ester Cerdeira Sabino,&nbsp;Carla Luana Dinardo","doi":"10.1007/s00277-025-06547-z","DOIUrl":"10.1007/s00277-025-06547-z","url":null,"abstract":"<div><p>Sickle cell disease (SCD) is characterized by painful vaso-occlusive crises (VOC), which occur due to the adhesion of sickled erythrocytes and leukocytes to the endothelium, leading to vascular obstruction and tissue ischemia. Recurrent VOC increases SCD morbidity, reduces quality of life, and results in frequent hospitalizations. While factors like HbF levels and alpha-thalassemia co-occurrence are known to influence the risk of VOC, the genetic basis of this phenotype remains underexplored. To address this, we conducted a Genome-Wide Association Study (GWAS) to identify genetic predictors of frequent VOC in SCD patients. The study focused on patients with the SS genotype, analyzing those who experienced three or more pain crisis hospitalizations annually. To account for population substructure, the top 10 principal components were included. The GWAS was performed using ENCORE and the Saige Logistic Mixed Model, adjusted for hydroxyurea treatment as a covariate, with a genome-wide significance threshold of 5 × 10^-8. The study included 125 cases and 1670 controls, revealing 9 significant SNPs. 8 were associated with the CTNNA2 gene (p-value = 7.77 × 10^-9), and 1 with METTL4 (p-value = 3.39 × 10^-8). These findings highlight the role of CTNNA2 and METTL4 in VOC hospitalizations, providing insights into the genetic underpinnings of SCD pain.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 8","pages":"4029 - 4035"},"PeriodicalIF":2.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06547-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and outcome of pediatric patients with high-risk acute promyelocytic leukemia, with special focus on risk factors of early death","authors":"Qinli Gao,&nbsp;Yiqiao Chen,&nbsp;Shaohua Le,&nbsp;Nainong Li,&nbsp;Cai Chen","doi":"10.1007/s00277-025-06528-2","DOIUrl":"10.1007/s00277-025-06528-2","url":null,"abstract":"<div><p>To evaluate the real-life outcome of pediatric high-risk acute promyelocytic leukemia (APL) after up-front treatment with all-trans retinoic acid (ATRA) and arsenic trioxide. Thirty-two pediatric patients diagnosed with high-risk APL from 2015 to 2022 were retrospectively studied. Of the 326 children with acute myeloid leukemia, 86 (26.4%) were diagnosed with APL. Thirty-two patients (37.2%) were designated to the high-risk group at diagnosis. Seven patients (21.8%) died during induction chemotherapy and the other 25 patients all achieved molecular complete remission (MCR) after induction chemotherapy. The underlying causes of early death (ED) were identified as follows: six cases of intracranial hemorrhage, and one case of pneumorrhagia accompanied by differentiation syndrome. Six ED cases developed fatal hemorrhage after the rapid initiation of ATRA. After a median follow-up duration of 50.1 months, the 5-year overall survival (OS) and event-free survival (EFS) rates were estimated to be (78.1 ± 7.3)% and (72.9 ± 8.5)%, respectively. Patients with ED had significantly higher rate of WBC count ≥ 50 × 10⁹/L (<i>P</i> = 0.027), female -to-male ration (<i>P</i> = 0.036), and prothrombin time (PT) ≥ 18 S (<i>P</i> = 0.017), along with shorter symptom-to-ATRA intervals (<i>P</i> = 0.014). ED remains the primary threat in high-risk APL, associated with elevated WBCs, prolonged PT, female gender and rapid disease progression. The inability of ATRA to prevent death in some cases may be due to individual variability and leukemia heterogeneity.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 8","pages":"4093 - 4099"},"PeriodicalIF":2.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06528-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"t(8;21)AML patients with RUNX1e6::RUNX1T19a splice variant have poor prognosis","authors":"Yuying Fan,&nbsp;Lanhui Chen,&nbsp;Sijin Liu,&nbsp;Jinwen Dang,&nbsp;Jianmei Chang,&nbsp;Caifeng Guo,&nbsp;Yang Xu,&nbsp;Wenzheng Guo,&nbsp;Hongwei Wang,&nbsp;Yanhong Tan","doi":"10.1007/s00277-025-06545-1","DOIUrl":"10.1007/s00277-025-06545-1","url":null,"abstract":"<div>\u0000 \u0000 <p>In t(8;21) AML, the <i>RUNX1::RUNX1T1</i> fusion gene (also called AML1-ETO or AE for short) exists in multiple splice variants, including <i>RUNX1::RUNX1T19a</i> (also called AML1-ETO9a or AE9a for short), <i>RUNX1::RUNX1T1tr</i> (also called AML1-ETOtr or AEtr for short), and <i>RUNX1::RUNX1T111a</i> (also called AML1-ETO11a or AE11a for short), These splice variants have distinct effects on cellular biological functions, which contribute to variability in patient prognoses.This study identifies a novel splice variant, <i>RUNX1e6::RUNX1T1</i> (also called AML1e6-ETO or AEe6 for short), which results from the fusion of exon 6 of RUNX1 with exon 2 of RUNX1T1 and demonstrates 100% coexpression with AE. Clinical studies indicate that patients expressing AEe6 exhibit poor prognostic outcomes, however, cellular assays reveal that AEe6 retains functionalities similar to those of AE in promoting apoptosis and inhibiting cellular proliferation. Notably, the splice variant AE9a is recognized as an independent prognostic factor for adverse outcomes. Consequently, this study further investigates the potential synergistic effects between AEe6 and AE9a. In a cohort of 82 patients, we observed a coexpression rate of 97% for these splice variants, referred to as AEe69a. Survival analyses revealed that patients expressing AEe69a exhibited the shortest OS and DFS, with median survival times of 13 and 9 months. Cellular studies demonstrated that, compared to wild-type K562-AE cells, K562-AEe69a cells promoted cell transition from G0/G1 to S/G2M phase and inhibited apoptosis and differentiation. Additionally, drug sensitivity analysis revealed that K562-AEe69a cells were less sensitive to the basic chemotherapeutic agent cytarabine than K562-AE, but more sensitive to the JAK2 selective inhibitor TG101209 than cytarabine.</p>\u0000 </div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 8","pages":"4081 - 4091"},"PeriodicalIF":2.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06545-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High complicated incidence of Gilbert's syndrome in patients with thalassemia: deserve earlier identification and less oversight.","authors":"Tianyi Lai, Yaonan Hong, Peicheng Wang, Qi Liu, Yingying Shen, Wanzhi Jiang, Xiawan Yang, Yiping Shen, Shan Liu, Dijiong Wu","doi":"10.1007/s00277-025-06549-x","DOIUrl":"https://doi.org/10.1007/s00277-025-06549-x","url":null,"abstract":"","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative longitudinal analysis of pulmonary function post-pediatric Allo-HSCT: benign vs. malignant diseases and early predictors","authors":"Hongjuan Li,&nbsp;Yan Gu,&nbsp;Xiaowei Zhao,&nbsp;Guoyu Ding,&nbsp;Yuqi Zhao,&nbsp;Xiaoyue Zhang,&nbsp;Yan Han,&nbsp;Xue Li,&nbsp;Hongmei Wang","doi":"10.1007/s00277-025-06537-1","DOIUrl":"10.1007/s00277-025-06537-1","url":null,"abstract":"<div><p>Pulmonary complications are a major cause of morbidity following pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, longitudinal pulmonary function test (PFT) trajectories and early predictors of dysfunction, particularly the interplay between underlying disease, PFTs, and graft-versus-host disease (GVHD), remain poorly understood. In this retrospective single-center study, we analyzed 233 children undergoing their first allo-HSCT with ≥ 100-day survival. Patients were categorized into benign (acquired aplastic anemia, <i>n</i> = 142) and malignant (leukemia/lymphoma, <i>n</i> = 91) groups. We assessed longitudinal PFTs over 24 months and used Kaplan-Meier and multivariate logistic regression analyses to identify early predictors (including 3-month PFT values and GVHD) for subsequent Obstructive (OVD) and Restrictive Ventilatory Disorders (RVD). Over a median follow-up of 33.1 months, the malignant group exhibited significantly slower FEV1 recovery, greater severity of RVD (<i>P</i> = 0.006) and diffusion impairment (<i>P</i> = 0.040), and higher cumulative incidences of OVD (HR = 3.34, <i>P</i> = 0.013) and RVD (HR = 2.16, <i>P</i> = 0.013). The malignant group also had significantly higher rates of acute (<i>P</i> &lt; 0.001) and chronic GVHD (<i>P</i> &lt; 0.001). In multivariate analysis, the strongest independent predictors for RVD were lower 3-month FVC%pred (OR = 0.85, <i>P</i> &lt; 0.001) and the presence of chronic GVHD (OR = 5.97, <i>P</i> = 0.027). For OVD, predictors were lower 3-month MEF50%pred (OR = 0.95, <i>P</i> = 0.030), acute GVHD (OR = 4.24, <i>P</i> = 0.014), and chronic GVHD (OR = 4.20, <i>P</i> = 0.018). Children with malignant diseases face a higher burden of post-HSCT pulmonary dysfunction, driven by both the underlying disease/treatment intensity and a higher incidence of GVHD. Early post-transplant PFTs (FVC%pred, MEF50%pred) and the development of GVHD are powerful, independent predictors of long-term ventilatory disorders. These findings underscore the need for routine, stratified longitudinal monitoring to facilitate early risk stratification and intervention.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 8","pages":"4201 - 4211"},"PeriodicalIF":2.4,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06537-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic mutations and the efficacy of immunosuppressive therapy in severe/very severe aplastic anemia and transfusion-dependent nonsevere aplastic anemia","authors":"Lei Ye,&nbsp;Li Zhang,&nbsp;Donglei Zhang,&nbsp;Xin Zhao,&nbsp;Yuan Li,&nbsp;Youzhen Xiong,&nbsp;Liwei Fang,&nbsp;Meili Ge,&nbsp;Jun Shi,&nbsp;Fengkui Zhang,&nbsp;Liping Jing","doi":"10.1007/s00277-025-06393-z","DOIUrl":"10.1007/s00277-025-06393-z","url":null,"abstract":"<div><p>This study aimed to assess the prevalence of somatic mutations (SMs) in severe/very severe aplastic anemia (V/SAA) and transfusion-dependent nonsevere aplastic anemia (TD-NSAA) prior to immunosuppressive therapy (IST) and their impact on treatment efficacy. Next-generation sequencing was used to analyze 114 hematopoiesis-related genes at disease onset in 312 patients. SMs were detected in 17.9% of cases, involving 25 genes, most commonly <i>DNMT3A</i> (14, 20.9%) and <i>BCOR</i> (9, 13.4%). SMs were more frequent in patients over 40 years old, predominantly with a single mutation of low variant allele frequency (&lt; 20%). Patients with SM were older and had lower lymphocyte counts. SMs did not significantly influence hematologic responses at 3, 6, or 12 months, relapse, progression, death, survival, or failure-free survival (<i>p</i> &gt; 0.05). Grouping patients by mutated genes revealed no significant differences in IST efficacy, though Group I (<i>PIGA</i> or <i>BCOR/BCORL1</i>) showed higher hematologic response rates in patients over 40 years of age. The cumulative incidence of clonal evolution was higher in Group II (<i>DNMT3A</i>, <i>TET2</i>, <i>ASXL1</i>, <i>FAT1</i>, or <i>RUNX1</i>), though not statistically significant. SMs in V/SAA and TD-NSAA were infrequent and did not affect IST outcomes or treatment decisions. However, the higher clonal evolution incidence in certain mutations warrants further research.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"104 8","pages":"3981 - 3992"},"PeriodicalIF":2.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-025-06393-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}