Journal of Hematology & Oncology最新文献

{"title":"Claudin18.2 positive gastric cancer: biology, tumor microenvironment, and therapeutic strategies.","authors":"Yi Xie,Pengfei Guan,Dan Liu,Zhi Peng,Xiaotian Zhang,Lin Shen,Yang Chen","doi":"10.1186/s13045-026-01803-9","DOIUrl":"https://doi.org/10.1186/s13045-026-01803-9","url":null,"abstract":"Claudin18.2 (CLDN18.2) is primarily expressed in gastric epithelial cells, where it plays a crucial role in maintaining the integrity of the gastric mucosal barrier. Its aberrant expression is closely associated with the initiation, progression, and tumor microenvironment (TME) remodeling of gastric cancer(GC). Clinical evidence indicates that CLDN18.2 is highly expressed in a substantial proportion of GC. Notably, its expression appears to be largely independent of established biomarkers such as human epidermal growth factor receptor 2 (HER2) and programmed death-ligand 1 (PD-L1). These features collectively suggest CLDN18.2 as a viable candidate for therapeutic intervention in GC. Increasing evidence suggests that CLDN18.2 positivity is associated with patient prognosis and may indicate a distinctive TME characterized by increased infiltration of CD4⁺ and CD8⁺ T cells, macrophages, and cancer-associated fibroblasts. This review systematically summarizes the biological characteristics of CLDN18.2 and the features of CLDN18.2-positive TME, and provides an overview of emerging therapeutic strategies targeting CLDN18.2. The aim is to elucidate the biological and clinical significance of CLDN18.2 in GC and to provide insights for optimizing future precision therapies.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"68 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in multiple myeloma: key updates from the ASH 2025 meeting.","authors":"Phyu Thin Naing,Muhamed Baljevic","doi":"10.1186/s13045-026-01802-w","DOIUrl":"https://doi.org/10.1186/s13045-026-01802-w","url":null,"abstract":"The therapeutic landscape of multiple myeloma (MM) is undergoing rapid transformation with the expansion of immune-based strategies. This editorial summarizes key MM abstracts presented at the American Society of Hematology (ASH) 2025 meeting, highlighting how bispecific antibodies (BsAbs), minimal residual disease (MRD)-adaptive approaches, and next-generation immune platforms are reshaping treatment across all MM disease stages. In newly diagnosed MM (NDMM), minimal residual disease (MRD)-adaptive consolidation with linvoseltamab in IMMUNOPLANT converted persistent MRD positivity to MRD negativity in all evaluable patients, supporting biologically guided treatment intensification. In transplant-ineligible (TIE) NDMM patients, TecLille showed that antibody-only therapy achieved deep responses with manageable infection risks. In early relapsed/refractory MM (RRMM), the pioneering phase III MajesTEC-3 trial demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits with BsAb teclistamab plus daratumumab compared to other standard triplets, with response rates approaching those historically observed with chimeric antigen receptor (CAR) T cell therapy. A novel rational BsAb combination of BsAb elranatamab anda cereblon E3 ligase modulatory drug (CELMoD) iberdomide in MagnetisMM-30 showed promising synergy despite cytopenias and updates to combination BsAb targeting in RedirecTT-1 demonstrated major activity in difficult to treat extramedullary myeloma (EMM). First-in-human inMMyCAR data showcased the forefront of engineered immune strategies, by introducing an in vivo CAR-T product as a proof-of-concept platform, with tremendous potential to streamline the access to therapy. Collectively, these studies signal a shift toward earlier and adaptive immunotherapy in all phases of MM disease, while underscoring the importance of infection mitigation and long-term safety evaluation.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"21 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved outcomes of the refined risk-stratification and risk-adapted therapy in children with acute myeloid leukemia: final results of the AIEOP AML 2013.","authors":"Franco Locatelli,Barbara Buldini,Martina Pigazzi,Carmelo Rizzari,Giuseppe Menna,Franca Fagioli,Manuela Tumino,Luca Lo Nigro,Paolo D'Angelo,Maria Giuseppina Cefalo,Valeria Paganelli,Luisa Strocchio,Marco Becilli,Marco Spinelli,Giovanna Giagnuolo,Francesco Saglio,Nicola Santoro,Concetta Micalizzi,Marco Zecca,Riccardo Masetti,Pietro Merli","doi":"10.1186/s13045-026-01798-3","DOIUrl":"https://doi.org/10.1186/s13045-026-01798-3","url":null,"abstract":"BACKGROUNDThe previous Italian national trial (AIEOP-AML-2002/01) on children with acute myeloid leukemia (AML) achieved a 3-year overall (OS) and event-free survival (EFS) of 72.3% and 59.1%, respectively. In this study (AIEOP-AML-2013), we evaluated if refined patient's stratification in 3 groups and a second induction with randomization could improve outcomes.METHODSIn the new AIEOP-AML-2013, patients were stratified into 3 groups [standard-(SR), intermediate-(IR) and high-risk (HR)] mainly according to genetic criteria and centralized assessment of multiparametric flow-cytometry measurable residual disease (MFC-MRD). The 1st induction course was common for all patients [idarubicin-cytarabine-etoposide (ICE)]. IR and HR patients were then randomized to receive either a 2nd ICE or the fludarabine-cytarabine- liposomal-doxorubicin (FLA-My) scheme as second induction. IR patients with HLA-compatible sibling, and all HR patients were consolidated with allogeneic hematopoietic stem cell transplantation (allo-HSCT), while the remaining IR and SR patients were consolidated with chemotherapy only. Data cut-off was February 1, 2024.RESULTSFrom June/2015 to June/2022, 371 patients were enrolled in the trial. Twenty-six children (7%) experienced primary induction failure, while only 3 patients died during the 2 induction courses. The cumulative incidence of 3-year non-relapse mortality in continuous complete remission was 6.8%. The proportion of patients allocated to the SR, IR, and HR groups were 19.5%, 22%, and 58.5%, respectively. Three-year cumulative incidence of relapse was 18.9%. The 3-year probabilities of OS and EFS were 83.9% and 68.5%, respectively, both values being significantly better (p = 0.001) than those of the AIEOP-AML-2002/01 study. The 3-year OS of SR, IR, and HR patients were 97.0%, 84.2%, and 79.4%, respectively, (p = 0.01). The probability of EFS did not differ in IR and HR randomized to receive either a 2nd ICE or the FLA-My scheme course. Levels of MRD after the 1st and 2nd induction course strongly influenced the EFS probability.CONCLUSIONSA significant improvement in the outcomes of children with de novo AML was obtained with refined risk-stratification and risk-adapted therapy. FLA-My did not offer any advantage over repeating a 2nd ICE as 2nd induction course.TRIAL REGISTRATIONThis study was registered in the European Clinical Trials Database (EudraCT 2014-000652-28).","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"135 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncoupling toxicity from efficacy in donor selection for allogeneic hematopoietic cell transplantation: a retrospective cohort study using double machine learning.","authors":"Rohtesh S Mehta,Yosra M Aljawai,Warren Fingrut,Portia Smallbone,Gabriela Rondon,Amanda Olson,Betul Oran,Partow Kebriaei,Richard E Champlin,Elizabeth J Shpall","doi":"10.1186/s13045-026-01800-y","DOIUrl":"https://doi.org/10.1186/s13045-026-01800-y","url":null,"abstract":"Haploidentical hematopoietic cell transplantation (HCT) offers potent graft-versus-tumor effects but is historically limited by higher non-relapse mortality (NRM) compared to matched unrelated (MUD) or related donors (MRD). To algorithmically decouple the competing risks of NRM and relapse, we analyzed 1,713 adult patients (MD Anderson discovery cohort) and 6,829 patients (registry replication cohorts) using a double machine-learning framework of Causal Survival Forests to estimate individualized treatment effects, while Random Survival Forests defined absolute prognostic risk. We found biological uncoupling of relapse and NRM: relapse was driven by disease biology, while NRM was governed by physiological reserve. Specifically, cardiovascular or cerebrovascular comorbidities acted as selective amplifiers of haploidentical toxicity-a \"vascular penalty\" that doubled mortality risk in the bootstrapped model (sub-distribution hazard ratio 2.09, 95% confidence interval 1.26-3.35). We developed a 3-factor nomogram (recipient age, vascular comorbidity, B-leader matching status) to identify an \"Optimized Haploidentical\" phenotype. Exploratory multivariable modeling suggested MUD consistently maximized predicted disease-free survival across all subgroups. Among haploidentical versus MRD comparisons, B-leader mismatch appeared to favor MRD across ages, while B-leader matched haploidentical donors in older patients (≥ 60 years) modeled near-equivalent DFS to MRD, representing a hypothesis-generating \"zone of equivalence\" requiring prospective validation.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"37 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil extracellular traps in the tumor microenvironment, metastasis, therapy, and beyond: advances, challenges, and perspectives.","authors":"Jingwen He,Zhaokai Zhou,Guangyang Cheng,Huabing Li,Jiaqi Tu,Zixuan Fan,Xiuting Qiu,Wenjie Chen,Yajun Chen,Ling Li,Chen Li,Zhengrui Li,Lina Chen,Qiong Lu","doi":"10.1186/s13045-026-01789-4","DOIUrl":"https://doi.org/10.1186/s13045-026-01789-4","url":null,"abstract":"Neutrophil extracellular traps (NETs), the DNA-protein structures released by neutrophils within the tumor microenvironment (TME), play a role in cancer that extends far beyond their traditional antimicrobial function. Specifically, NETs exert multifaceted and context-dependent effects on tumor progression, metastasis, immune regulation, and therapeutic response, showing their robust activity in shaping the complex landscape of tumor biology. This review systematically elucidates how NETs promote tumorigenesis by inducing DNA damage and epithelial-mesenchymal transition (EMT), and drive metastatic spread through mechanisms such as trapping circulating tumor cells, remodeling the pre-metastatic microenvironment, and reactivating dormant cells. Concurrently, NETs shape an immunosuppressive TME by modulating T cells, NK cells, and macrophages, while mediating resistance to chemotherapy, radiotherapy, and immunotherapy. Based on these mechanisms, targeting NET formation (such as inhibiting PAD4 or NE) or degrading their structures (such as using DNase I) has emerged as a potential strategy to enhance the efficacy of existing therapies. Therefore, deepening the understanding of the multifunctional regulatory networks underlying NETs within the TME holds significant implications for developing novel precision cancer therapies.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"63 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147685039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T therapy moving to first-line in multiple myeloma: latest updates from the 2025 ASH annual meeting.","authors":"Chuanying Geng,Wenming Chen,Hong-Hu Zhu","doi":"10.1186/s13045-026-01793-8","DOIUrl":"https://doi.org/10.1186/s13045-026-01793-8","url":null,"abstract":"CAR-T therapy is rapidly reshaping the treatment paradigm of multiple myeloma (MM). At the 2025 ASH Annual Meeting, pivotal trials demonstrated marked efficacy across both relapsed/refractory and newly diagnosed settings. In KarMMa-3, a subgroup analysis of older patients (≥ 70 years) showed idecabtagene vicleucel significantly improved outcomes versus standard care: overall response rate (ORR) 81.6% vs. 48.1%, median progression-free survival (PFS) 18.9 vs. 5.7 months, with median overall survival (OS) not reached in either arm. CARTITUDE-4 showed superior 30-month PFS (71.0% vs. 43.2%), while iMMagine-1 reported an ORR of 97% with 93% minimal residual disease negativity. Notably, frontline CAR-T studies achieved unprecedented outcomes, including 100% ORR, stringent complete response rates approaching 94-97%, and 30-month PFS and OS rates of 88-92%. Together, these data support a paradigm shift toward earlier integration of CAR-T therapy in MM management.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"21 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147666521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing next-generation CAR-macrophages against solid tumors: challenges and potential strategies.","authors":"Yizhao Chen,Lucheng Zhou,Xinlei Chen,Shuai Wang,Weiwei Chen,Zixuan Li,Ji Qiu,Ruilin Li,Jiajie Tu,Ning Lin","doi":"10.1186/s13045-026-01792-9","DOIUrl":"https://doi.org/10.1186/s13045-026-01792-9","url":null,"abstract":"Chimeric antigen receptor macrophage (CAR-M) therapy has emerged as a highly promising novel platform in solid tumor immunotherapy. Leveraging its inherent tumor-homing capacity, potent phagocytic function, and potential to remodel the tumor microenvironment (TME), CAR-M offers a new strategic approach to address the limitations faced by CAR-T therapy in solid tumors, such as poor infiltration and immunosuppression. Despite these mechanistic advantages, clinical outcomes with first-generation CAR-M constructs have been modest, largely due to their limited in vivo persistence and effector activity. In this review, we summarize the core challenges limiting the efficacy and clinical application of CAR-M, and provide an in-depth discussion of engineering strategies aimed at enhancing its anti-tumor activity through optimization of the CAR molecular structure. Beyond CAR-M engineering, we also outline recent advances in combining CAR-M with other therapeutic modalities and discussing their underlying synergistic mechanisms. Looking forward, we highlight next-generation CAR-M platforms, such as in vivo edited CAR-M and CAR-monocytes, which aim to simplify manufacturing, reduce costs, and enable more precise immune modulation. Although challenges remain in manufacturing, durability of response, and safety, continuous technological innovation and rational combination strategies are accelerating the translation of CAR-M therapy from proof-of-concept toward clinical application, holding promise for opening new avenues in solid tumor treatment.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"21 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo CAR-T cell therapy: latest updates from 2025 ASH annual meeting.","authors":"Pan Gao,Jun Liu,Jun Ma,Hengrui Ma,Ya Zhang","doi":"10.1186/s13045-026-01787-6","DOIUrl":"https://doi.org/10.1186/s13045-026-01787-6","url":null,"abstract":"Chimeric antigen receptor (CAR)-T cell therapy has demonstrated remarkable efficacy in treating hematological malignancies. However, this approach faces substantial limitations, including protracted manufacturing periods, elevated costs, restricted patient eligibility attributable to manufacturing constraints, and intolerate lymphodepleting preconditioning regimens. To address these challenges, in vivo CAR-T cell therapy has emerged as a promising alternative, directly engineering immune cells within the patient through targeted delivery systems such as engineered viral vectors, lipid nanoparticles, and other non-viral platforms. This approach offers immediate administration and enhanced scalability compared with ex vivo methods. The 2025 American Society of Hematology annual meeting presented multiple abstracts advancing this field, with this review focusing on studies demonstrating novel delivery system innovations, including engineered lentiviral vectors and non-viral platforms, as well as expanded therapeutic applications beyond oncology to autoimmune diseases. By integrating these conference presentations with recent peer-reviewed literature, this paper summarizes the current landscapes of in vivo CAR-T cell therapy presented at the conference.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"8 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agent-specific, histopathology-stratified hematologic malignancy risk among dpp-4 inhibitors, glp-1 receptor agonists, and SGLT2 inhibitors: a network meta-analysis of 270,471 participants.","authors":"Pao-Yen Lin,Bing-Syuan Zeng,Jiann-Jy Chen,Bing-Yan Zeng,Mein-Woei Suen,Chao-Ming Hung,Chih-Wei Hsu,Brendon Stubbs,Yen-Wen Chen,Tien-Yu Chen,Wei-Te Lei,Shih-Pin Hsu,Yow-Ling Shiue,Kuan-Pin Su,Cheng-Ta Li,Hung-Yu Wang,Ping-Tao Tseng,Chih-Sung Liang","doi":"10.1186/s13045-026-01788-5","DOIUrl":"https://doi.org/10.1186/s13045-026-01788-5","url":null,"abstract":"","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"62 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in first-line treatment for primary central nervous system lymphoma: highlights from the 2025 ASH annual meeting.","authors":"Rong Wei,Shenmiao Yang","doi":"10.1186/s13045-026-01786-7","DOIUrl":"https://doi.org/10.1186/s13045-026-01786-7","url":null,"abstract":"Advances in targeted therapies for newly diagnosed primary central nervous system lymphoma (PCNSL) were a key highlight at the 2025 ASH Annual Meeting. While high-dose methotrexate (HD-MTX) remains the cornerstone of PCNSL treatment, the integration of BTK inhibitors, immunomodulators, and novel agents-such as selinexor and anti-PD-1 antibodies-is reshaping the first-line management paradigm. These emerging combinations are improving response rates and survival, paving the way for more effective strategies. Here, we provide a timely synthesis of these pivotal updates presented at ASH 2025.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"47 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}