Annals of Hematology最新文献

{"title":"Neuro-toxoplasmosis in haploidentical haematopoietic stem cell transplant.","authors":"Marco Galli, Lorenzo Masina, Gabriele Magliano, Enrico Morello, Evelyn Van Hauwermeiren, Michele Malagola, Mirko Farina, Vera Radici, Domenico Russo, Daniele Avenoso","doi":"10.1007/s00277-025-06281-6","DOIUrl":"https://doi.org/10.1007/s00277-025-06281-6","url":null,"abstract":"<p><p>Allogeneic haematopoietic stem cell transplant is a routine procedure for several haematological disorders though infections are the main cause of morbidity and mortality. Rare infections, such as protozoan reactivations, can be life-threatening and clinicians should be aware of these possibilities. Herein, we present a case of neuro-toxoplasmosis post haploidentical haematopoietic stem cell transplant.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498070","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":"Sequential combined bypassing therapy in haemophilia patients with high titer inhibitors: surgical experience.","authors":"Bingjie Ding, Xuewen Song, Liu Liu, Xiaoying Niu, Mengjuan Li, Yuanyuan Zhang, Shujun Shao, Ao Xia, Jingyuan Liu, Jing Zhang, Po Li, Fan Zhang, Guancong Liu, Zhehuang Li, Peng Zhang, Hu Zhou","doi":"10.1007/s00277-025-06265-6","DOIUrl":"https://doi.org/10.1007/s00277-025-06265-6","url":null,"abstract":"<p><p>Sequential combination bypass therapy (SCBT) is an effective treatment option for haemophilia patients with inhibitors; however, its safety, efficacy, and cost have largely have yet to be systematically evaluated. To address this question, we retrospectively analyzed the medical records of 14 haemophilia patients with high titer inhibitors who underwent surgery. The patients with high inhibitors were treated with two SCBT regimens by optimizing doses of the recombinant activated factor VII (rFVIIa) and prothrombin complex concentrate (PCC). The effectiveness and safety of the two SCBT regimens were evaluated. In addition, rFVIIa and PCC factor consumption and costs were also compared. The median age of the 14 patients was 30.00 (27.25-42.75) years. They all underwent major surgeries, with 85.71% (12/14) was orthopedic surgeries related to hemophilic arthropathy. Four patients were treated using regimen 1 and ten with regimen 2. Results showed that regimen 2 exhibited a higher haemostatic efficiency (90% vs. 75% intraoperative and 90% vs. 50% postoperative) and a 28.0% reduction in economic costs (863,604.68 RMB vs. 621,756.62 RMB). All patients after surgery had no prothrombin time extension, 7.14% had fibrinogen and platelet count decreases, and 57.14% had D-dimer increases that returned to baseline within 5-7 days after SCBT. The study shows that regimen 2 as an optimized SCBT regimen is an efficient approach to secure haemostasis for haemophilia patients with high titer inhibitors in the perioperative period, rather than regimen 1. The findings can help design future clinical studies and provide more reliable data and implementation advice.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498072","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":"Is there still a place for autologous salvage transplantation in relapsed/refractory multiple myeloma in the era of novel therapies?","authors":"Simone Karp, Karolin Trautmann-Grill, Paul Warncke, Dominik Zolnowski, Christoph Röllig, Marcel Pannach, Jessica Zinn, Frank Kroschinsky, Anke Morgner, Malte von Bonin, Annette Hänel, Regina Herbst, Stephan Fricke, Martin Bornhäuser, Mathias Hänel, Raphael Teipel","doi":"10.1007/s00277-025-06262-9","DOIUrl":"https://doi.org/10.1007/s00277-025-06262-9","url":null,"abstract":"<p><p>For patients (pts) with relapsed or refractory multiple myeloma (RRMM) after previous autologous hematopoietic cell transplantation (AHCT), novel agents, cellular and immunotherapies are increasingly available. Options for second-line treatment mostly include triplet regimens based on proteasome inhibitors, immunomodulatory drugs and anti-CD38 monoclonal antibodies and since recently also CAR T cells. The importance of autologous salvage transplantation (retransplantation, Re-AHCT) has significantly decreased in recent years due to the availability of many new treatment options. Therefore, we performed a retrospective analysis of 171 pts cases with RRMM who received Re-AHCT between 2002 and 2021. With a median follow-up of 74.7 months, the 5-year rates of progression-free survival (PFS) and overall survival (OS) were 18% (median 20.6 months) and 57% (median 65.0 months), respectively, the 100-day mortality rate was 4%. Multivariate analysis identified R-ISS stage and duration of previous response (DoR) as independent prognostic factors for PFS and OS. While the revealed high-risk population (R-ISS stage II/III, DoR ≤ 24 months) was associated with a significantly worse PFS (HR 2.728) and OS (HR 3.129), the low-risk group (R-ISS I, DoR > 24 months) achieved a median PFS and OS of 45.0 months and 80.2 months, respectively. Therefore, Re-AHCT could remain an option in such prognostically favorable pts with RRMM even in the era of novel therapies especially when more potent treatment modalities are not available.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498068","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":"Antibiotic lock therapy for the treatment of peripherally inserted central venous catheter-related bloodstream infection in patients with hematological malignancies: a single center retrospective study.","authors":"Qin Zhang, Yujia Huo, Chengfei Li, Qinggang Sun, Xi Xi, Rui Sun, Qingju Sun, Meijuan Jiang, Guang Li","doi":"10.1007/s00277-025-06263-8","DOIUrl":"https://doi.org/10.1007/s00277-025-06263-8","url":null,"abstract":"<p><p>Catheter-related bloodstream infections represent one of the most prevalent complications in patients with peripherally inserted central venous catheters (PICCs). The application of antibiotic lock therapy (ALT), particularly in patients with hematological malignancies, has not been well documented. We aim to share our experience on ALT for these patients and to evaluate its effectiveness and safety. All cases of patients with hematological malignancies who had PICC from January 2018 to October 2024 were retrospectively reviewed. Microbiologic data of PICC-related bloodstream infections (PRBSIs) were collected. A comparison was made between patients managed with ALT and those without it. Factors affecting PICC removal were also explored. A total of 45 patients experienced 67 episodes of PRBSIs, yielding an incidence rate of 2.98 per 1,000 PICC days. The median time of PRBSI onset was 42 days. Predominant pathogens included Gram-negative bacilli (49.3%) and Gram-positive cocci (35.8%). The catheter salvage rate was significantly higher at 76.5% when ALT was combined with systemic antibiotic therapy (SAT), compared to 51.5% for SAT alone (p = 0.033). 3 death events (3/34) compared with 4 death events (4/33) occurred in each therapeutic regimen (p = 0.709). Elevated procalcitonin levels (> 2ng/ml) and inadequate empirical therapy were risk factors for PICC removal; conversely, ALT served as a protective factor against it. ALT in combination with systemic antibiotics is a safe and effective approach for managing PRBSIs in patients with hematological malignancies, helping to avoid unnecessary catheter removal and could be considered in clinical practice when catheter retention is desired.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490436","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":"The optimal time and clinical implications of measurable residual disease detection in mantle cell lymphoma.","authors":"Yuting Yan, Yanshan Huang, Ying Yu, Zhongchao Duan, Yuxi Li, Rui Lyu, Tingyu Wang, Wenjie Xiong, Yi Wang, Qi Wang, Wei Liu, Gang An, Weiwei Sui, Yan Xu, Wenyang Huang, Mu Hao, Dehui Zou, Lugui Qiu, Shuhua Yi","doi":"10.1007/s00277-025-06246-9","DOIUrl":"https://doi.org/10.1007/s00277-025-06246-9","url":null,"abstract":"<p><p>Recent advances in measurable residual disease (MRD) technology have significantly enhanced predictive accuracy for outcomes in various hematologic malignancies, serving as a crucial surrogate endpoint. However, in mantle cell lymphoma (MCL), identifying the optimal timing for MRD assessment and understanding the prognostic implications of MRD dynamics remain challenging, primarily due to limited extensive MRD data. Our study encompassed 102 patients with MCL, all presenting with clonal B-cell involvement in bone marrow as determined by multiparametric flow cytometry (MFC). MRD evaluations were conducted every two cycles. 75.5% (77/102) achieved MRD negativity during induction therapy. We found the MRD status at the end of four cycles treatment had the best predictive ability for survival (HR = 3.2, C-index = 0.664). 32 of 77 patients (41.6%) had a rapid tumor burden reduction and achieved MRD negativity within two cycles treatment. Notably, this swift shift to MRD negativity was observed more frequently in patients classified as MIPI high-risk. However, this rapid clearance of MRD did not confer any prognostic benefit to these patients. Subgroup analyses revealed that MRD negativity held prognostic value in almost all categories, except for those with blastoid/pleomorphic morphology. MRD assessment serves as a valuable complement to the traditional response evaluation, particularly benefiting for patients attaining partial remission. These findings highlighted the importance of MRD detection during response evaluation of MCL therapy and determined that after four treatment cycles is the best MRD detection timepoint.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490439","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":"Tumor microenvironment as a novel therapeutic target for lymphoid leukemias.","authors":"Shahrzad Mousavi, Soheil Nouri, Arezoo Sadeghipour, Amir Atashi","doi":"10.1007/s00277-025-06237-w","DOIUrl":"https://doi.org/10.1007/s00277-025-06237-w","url":null,"abstract":"<p><p>Lymphoid leukemias represent a significant global health burden, leading to substantial morbidity and mortality. The intricate interplay between leukemic cells and their surrounding tumor microenvironment (TME) is pivotal in disease initiation, progression, and therapeutic resistance. Comprising a dynamic milieu of stromal, immune, and leukemic cell populations, the TME orchestrates a complex network of signaling pathways and molecular interactions that foster leukemic cell survival and proliferation while evading immune surveillance. The crosstalk between these diverse cellular components within the TME not only fuels tumor progression but also confers resistance to conventional therapies, including the development of multi-drug resistance (MDR). Recognizing the pivotal role of the TME in shaping disease outcomes, novel therapeutic approaches targeting this dynamic ecosystem have emerged as promising strategies to complement existing anti-leukemic treatments. As a result, drugs that target the TME have been developed as complementary strategies to those that directly attack tumor cells. Thus, a detailed understanding of the TME components and their interactions with tumor cells is critical. Such knowledge can guide the design and implementation of novel targeted therapies for lymphoid leukemias.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490440","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":"A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD.","authors":"Wataru Kitamura, Keiko Fujii, Mitsuru Tsuge, Toshiharu Mitsuhashi, Hiroki Kobayashi, Chihiro Kamoi, Akira Yamamoto, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Ken-Ichi Matsuoka, Nobuharu Fujii, Yoshinobu Maeda","doi":"10.1007/s00277-025-06269-2","DOIUrl":"https://doi.org/10.1007/s00277-025-06269-2","url":null,"abstract":"<p><p>Therapies that effectively suppress graft-versus-host disease (GVHD) without compromising graft-versus-leukemia/lymphoma (GVL) effects is important in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic malignancies. Geranylgeranylacetone (GGA) is a main component of teprenone, a gastric mucosal protectant commonly used in clinical practice. In preclinical models, GGA suppresses proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), which are associated with GVHD as well as induces thioredoxin-1 (Trx-1), which suppresses GVHD while maintaining GVL effects. Here, we investigated whether the addition of teprenone to standard GVHD prophylaxis could reduce the cumulative incidence of severe acute GVHD (aGVHD) without attenuating GVL effects. This open-label, randomized clinical trial enrolled 40 patients (21 control and 19 teprenone group) who received allo-HSCT between May 2022 and February 2023 in our institution. Patients in the teprenone group received 50 mg of teprenone orally thrice daily for 21 days from the initiation of the conditioning regimen. The cumulative incidence of severe aGVHD by day 100 after allo-HSCT was not significantly different in the two groups (27.9 vs. 16.1%, p = 0.25). The exploratory studies revealed no obvious changes in Trx-1 levels, but the alternations from baseline in IL-1β and TNF-α levels at day 28 after allo-HSCT tended to be lower in the teprenone group. In conclusion, we could not demonstrate that teprenone significantly prevented the development of severe aGVHD. Discrepancy with preclinical model suggests that appropriate dose of teprenone may be necessary to induce the expression of antioxidant enzymes that suppress severe aGVHD. Clinical Trial Registration number:jRCTs 061210072.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490434","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":"Global, regional and national temporal trends in incidence and mortality of non-Hodgkin lymphoma from 1992 to 2021: an age-period-cohort analysis.","authors":"Shanshan Tang, Jin Cao, Denan Jiang, Longzhu Zhu, Zeyu Luo, Shiyi Shan, Jiali Zhou, Jiayao Ying, Jing Wu, Peige Song, Wei Li","doi":"10.1007/s00277-025-06261-w","DOIUrl":"10.1007/s00277-025-06261-w","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to provide an overview of temporal trends in incidence and mortality of non-Hodgkin lymphoma (NHL) from 1992 to 2021 at global, regional, and national levels, with a special focus on their associations with age, period and cohort.</p><p><strong>Methods: </strong>Data were obtained from the Global Burden of Disease Study 2021. We presented temporal trends in NHL incidence and mortality for the world and 204 countries and territories from 1992 to 2021. An age-period-cohort (APC) model was adopted to estimate net drifts (overall annual percentage change), local drifts (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks.</p><p><strong>Results: </strong>The global age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) for NHL were 7.14 (95% uncertainty interval [UI]: 6.58, 7.66) and 3.19 (95% UI: 2.93, 3.44) per 100,000 population in 2021, respectively. From 1992 to 2021, the global net drift of incidence rate was 0.11% (95% confidential intervals [CI]: 0.07%, 0.15%) per year, ranging from - 0.60% (95% CI: -0.66%, -0.54%) in high socio-demographic index (SDI) region to 1.51% (95% CI: 1.46%, 1.57%) in middle SDI region, with 100 countries and territories presenting increasing trends. Similar patterns can be found in the net drift of mortality rate, with 19 countries and territories showing upward trends. Age effects illustrated that incidence and mortality risks progressively increased with advancing age across different SDI regions. Period effects on incidence presented rising risks in high-middle, middle and low-middle SDI regions, whereas on mortality exhibited persistent downward trends in high and high-middle SDI regions. High-middle and middle SDI regions presented initially unfavourable and then favourable trends in incidence and mortality risks across successive birth cohorts. A strong heterogeneity was found in age, period and cohort effects on incidence and mortality across countries.</p><p><strong>Conclusions: </strong>Despite observing an increasing temporal trend in NHL incidence, coupled with a declining trend in mortality, NHL represented a substantial public health challenge worldwide. Temporal trends in NHL were not completely commensurate with socioeconomic development and varied widely across countries. Timely intervention should be conducted, especially for middle-aged and aged individuals.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482077","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":"Biomarkers in clonal haematopoiesis of indeterminate potential (CHIP) linking cardiovascular diseases, myeloid neoplasms and inflammation.","authors":"Hui Shan Valerie Tan, Haowen Jiang, Samuel Sherng Young Wang","doi":"10.1007/s00277-025-06244-x","DOIUrl":"https://doi.org/10.1007/s00277-025-06244-x","url":null,"abstract":"<p><p>There is increasing evidence that points to ubiquity of clonal haematopoiesis of indeterminate potential (CHIP) especially with rising age. CHIP has been associated with a multitude of inflammatory, cardiovascular and malignant conditions. In this review article, we evaluate the current literature on CHIP and clinical associations with cardiovascular and haematological diseases. We also discuss high risk features of CHIP that predispose to haematological malignancies, as well as further zoom in on the association between clonal haematopoiesis and therapy-related myeloid neoplasm (tMN). CHIP increases risk of atherosclerotic cardiovascular disease and other cardiovascular conditions such as heart failure, arrhythmias and valvular disease. Hematopoietic clones with mutations in TP53 and spliceosome gene U2AF1 in particularly have repeatedly been shown to increase risk for AML. Other factors such as increased clonal size i.e. variant allele fraction (VAF), clonal complexity have also been shown to increase risk for haematological malignancy. In this comprehensive review, we consolidate the most recent advancements in the understanding of clonal haematopoiesis of indeterminate potential (CHIP) and its associations with cardiovascular and haematological disease. This review is also one of the first to focus on potential biochemical markers routinely utilized in clinical practice that may suggest a more sinister progression of CHIP. We hope to provide physicians with a nuanced perspective on the evolving landscape of CHIP, and offering valuable insights into its clinical implications and potential prognostic indicators.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481966","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":"The mutational landscape and its longitudinal dynamics in relapsed and refractory classic Hodgkin lymphoma.","authors":"Hanno Witte, Axel Künstner, Thomas Hahn, Veronica Bernard, Stephanie Stölting, Kathrin Kusch, Kumar Nagarathinam, Cyrus Khandanpour, Nikolas von Bubnoff, Arthur Bauer, Michael Grunert, Svenja Hartung, Annette Arndt, Konrad Steinestel, Hartmut Merz, Hauke Busch, Alfred C Feller, Niklas Gebauer","doi":"10.1007/s00277-025-06274-5","DOIUrl":"https://doi.org/10.1007/s00277-025-06274-5","url":null,"abstract":"<p><p>In classic Hodgkin-lymphoma (cHL), only a few cases recur, and only a limited fraction of patients is primary-refractory to standard-polychemotherapy. Underlying genomic features of unfavorable clinical courses remain sparsely characterized. Here, we investigated the genomic characteristics of primary-refractory/relapsed cHL in contrast with responders. Therefore, ultra-deep next-generation panel-sequencing was performed on a total of 59 FFPE-samples (20 responders, 26 relapsed (rHL: 11 initial-diagnosis, 15 relapse) and 13 primary-refractory (prHL: 8 initial-diagnosis, 5 progression) from 44 cHL-patients applying a hybrid-capture approach. We compared samples associated with distinct disease courses concerning their oncogenic drivers, mutational signatures, and perturbed pathways. Compared to responders, mutations in genes such as PMS2, PDGFRB, KAT6A, EPHB1, and HGF were detected more frequently in prHL/rHL. Additionally, we observed that in rHL or prHL, BARD1-mutations occur, whereas ETV1, NF1, and MET-mutations were eliminated through clonal selection. A significant enrichment of non-synonymous variants was detected in prHL compared to responders and a significant selection process in favor of NOTCH-pathway mutations driving rHL or prHL was observed. However, our analysis revealed a negative selection process for non-synonymous variants affecting the hippo-pathway. This study delineates distinct mutational signatures between responders and rHL/prHL, whilst illustrating longitudinal dynamics in mutational profiles using paired samples. Further, several exploitable therapeutic vulnerabilities for rHL and prHL were identified.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482092","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}