Experimental Hematology & Oncology最新文献

{"title":"Targeting DNA helicase CMG complex and NFκB2-driven drug-resistant transcriptional axis to effectively treat KRAS^G12D-mutated pancreatic cancer.","authors":"Jeffrey Xiao, Joshua Kim, Brandon Park, David J Baylink, Cedric Kwon, Victoria Tran, Scott Lee, Kevin Codorniz, Laren Tan, Pamela Lobo Moreno, Amy Schill-Depew, Saied Mirshahidi, David De Semir, Diana Hanna, Kiran Naqvi, Huynh Cao, Chien-Shing Chen, Joanne Xiu, Heinz-Josef Lenz, Hamid Mirshahidi, Mark E Reeves, Yi Xu","doi":"10.1186/s40164-025-00669-w","DOIUrl":"10.1186/s40164-025-00669-w","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a 5-year overall survival (OS) rate of approximately 12%. More than 90% of PDAC patients harbor oncogenic mutations in the Kirsten rat sarcoma viral homolog (KRAS) gene. MRTX1133 (MRTX), a novel inhibitor of KRAS^G12D (the most common KRAS mutation found in pancreatic and colon cancers) has shown promise as a therapeutic agent. To address reported resistance to MRTX, we adapted our anti-leukemia co-targeting strategy and evaluated a combination of MRTX and Bedaquiline (BED), an FDA-approved inhibitor of mitochondrial ATP production, in in vitro human PDAC models. The combination of MRTX and BED demonstrated enhanced cytotoxic effects by disrupting all 11 genes within the DNA helicase family (CMG complex: CDC45-MCM-GINS), which are essential for initiating DNA replication and regulating cell cycle progression. Notably, real-world data analysis from Caris Life Sciences and NCI-TCGA database revealed that low transcriptomic expression of the DNA helicase CMG complex was significantly associated with prolonged survival (e.g., low CDC45 expression and low GINS2 expression with greater than 8 months longer overall survival) in PDAC patients with KRAS^G12 mutations (N = 9,717; P < 0.00001). However, this combination therapy also triggered strong pro-survival nuclear reprogramming. This effect was mediated by significant genetic activation of an NFκB2-DDIT (DNA damage-induced transcript) axis, which supported tumor chromosomal integrity and DNA repair mechanisms. To overcome NFκB2-driven resistance mechanisms, we explored a triple-targeting strategy that addresses metabolic and genomic plasticity in addition to actively intercepting cell division. This approach combines MRTX1133, Bedaquiline, and the NFκB2 inhibitor SN52, offering a novel therapeutic avenue to treat aggressive pancreatic cancer and potentially improve patient outcomes.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"79"},"PeriodicalIF":9.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MENIN inhibitor-based therapy in acute leukemia: latest updates from the 2024 ASH annual meeting.","authors":"Jiewen Sun, Wenjuan Yu, Xiang Zhang","doi":"10.1186/s40164-025-00668-x","DOIUrl":"10.1186/s40164-025-00668-x","url":null,"abstract":"<p><p>Menin inhibitors (MENINis) represent a novel and promising class of therapeutic agents for acute leukemia (AL). AL subtypes driven by overexpressed HOXA9/MEIS1, such as those characterized by KMT2A-rearranged (KMT2Ar) or NPM1-mutated (NPM1m) AL, display sensitivity to MENINi. Consequently, approximately 40-50% of acute myeloid leukemia (AML) and 5-15% of acute lymphoblastic leukemia (ALL) patients may potentially benefit from MENINi-based therapy. At the 2024 ASH annual meeting, updated clinical data regarding monotherapy with MENINis in AL, including revumenib, bleximenib, enzomenib and BN104, were presented. Moreover, combination therapies based on MENINis were also reported to be highly effective in refractory/relapsed, or newly diagnosed KMT2Ar- and NPM1m-AML patients. Evidently, MENINis have demonstrated a considerable efficacy in KMT2Ar- and NPM1m-AML patients with a well-tolerance. Furthermore, the therapeutic effects of venetoclax plus azacitidine or \"3 + 7\" regimens were further enhanced by the addition of MENINis in KMT2Ar- and NPM1m-AML patients. Therefore, MENINis offer new therapeutic prospects for AML patients, particularly for those with high-risky and poor-prognostic on-target subtypes.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"78"},"PeriodicalIF":9.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy in breast cancer: current landscape and emerging trends.","authors":"Ran Ran, Xi Chen, Jin Yang, Binghe Xu","doi":"10.1186/s40164-025-00667-y","DOIUrl":"10.1186/s40164-025-00667-y","url":null,"abstract":"<p><p>Breast cancer remains one of the most prevalent malignancies worldwide, underscoring an urgent need for innovative therapeutic strategies. Immunotherapy has emerged as a transformative frontier in this context. In triple-negative breast cancer (TNBC), the combination of immunotherapy based on PD-1/PD-L1 immune checkpoint inhibitors (ICIs) with chemotherapy has proven efficacious in both early and advanced clinical trials. These encouraging results have led to the approval of ICIs for TNBC, opening up new therapeutic avenues for challenging-to-treat patient populations. Furthermore, a multitude of ongoing trials are actively investigating the efficacy of immunotherapy-based combinations, including ICIs in conjunction with chemotherapy, targeted therapy and radiation therapy, as well as other novel strategies such as bispecific antibodies, CAR-T cells and cancer vaccines across all breast cancer subtypes, including HR-positive/HER2-negative and HER2-positive disease. This review provides a comprehensive overview of current immunotherapeutic approaches in breast cancer, highlighting pivotal findings from recent clinical trials and the potential impact of these advancements on patient outcomes.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"77"},"PeriodicalIF":9.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developments in nanotechnology approaches for the treatment of solid tumors.","authors":"Jacopo Venturini, Abhijit Chakraborty, Mehmet A Baysal, Apostolia M Tsimberidou","doi":"10.1186/s40164-025-00656-1","DOIUrl":"10.1186/s40164-025-00656-1","url":null,"abstract":"<p><p>Nanotechnology has revolutionized cancer therapy by introducing advanced drug delivery systems that enhance therapeutic efficacy while reducing adverse effects. By leveraging various nanoparticle platforms-including liposomes, polymeric nanoparticles, and inorganic nanoparticles-researchers have improved drug solubility, stability, and bioavailability. Additionally, new nanodevices are being engineered to respond to specific physiological conditions like temperature and pH variations, enabling controlled drug release and optimizing therapeutic outcomes. Beyond drug delivery, nanotechnology plays a crucial role in the theranostic field due to the functionalization of specific materials that combine tumor detection and targeted treatment features. This review analyzes the clinical impact of nanotechnology, spanning from early-phase trials to pivotal phase 3 studies that have obtained regulatory approval, while also offering a critical perspective on the preclinical domain and its translational potential for future human applications. Despite significant progress, greater attention must be placed on key challenges, such as biocompatibility barriers and the lack of regulatory standardization, to ensure the successful translation of nanomedicine into routine clinical practice.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"76"},"PeriodicalIF":9.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation immunotherapeutic approaches for blood cancers: Exploring the efficacy of CAR-T and cancer vaccines.","authors":"Kiavash Hushmandi, Abbas Ali Imani Fooladi, Russel J Reiter, Najma Farahani, Liping Liang, Amir Reza Aref, Noushin Nabavi, Mina Alimohammadi, Le Liu, Gautam Sethi","doi":"10.1186/s40164-025-00662-3","DOIUrl":"10.1186/s40164-025-00662-3","url":null,"abstract":"<p><p>Recent advancements in immunotherapy, particularly Chimeric antigen receptor (CAR)-T cell therapy and cancer vaccines, have significantly transformed the treatment landscape for leukemia. CAR-T cell therapy, initially promising in hematologic cancers, faces notable obstacles in solid tumors due to the complex and immunosuppressive tumor microenvironment. Challenges include the heterogeneous immune profiles of tumors, variability in antigen expression, difficulties in therapeutic delivery, T cell exhaustion, and reduced cytotoxic activity at the tumor site. Additionally, the physical barriers within tumors and the immunological camouflage used by cancer cells further complicate treatment efficacy. To overcome these hurdles, ongoing research explores the synergistic potential of combining CAR-T cell therapy with cancer vaccines and other therapeutic strategies such as checkpoint inhibitors and cytokine therapy. This review describes the various immunotherapeutic approaches targeting leukemia, emphasizing the roles and interplay of cancer vaccines and CAR-T cell therapy. In addition, by discussing how these therapies individually and collectively contribute to tumor regression, this article aims to highlight innovative treatment paradigms that could enhance clinical outcomes for leukemia patients. This integrative approach promises to pave the way for more effective and durable treatment strategies in the oncology field. These combined immunotherapeutic strategies hold great promise for achieving more complete and lasting remissions in leukemia patients. Future research should prioritize optimizing treatment sequencing, personalizing therapeutic combinations based on individual patient and tumor characteristics, and developing novel strategies to enhance T cell persistence and function within the tumor microenvironment. Ultimately, these efforts will advance the development of more effective and less toxic immunotherapeutic interventions, offering new hope for patients battling this challenging disease.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"75"},"PeriodicalIF":9.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling neutropenic enterocolitis: insights from gut microbiota, and intestinal barrier analyses.","authors":"Natacha Kapandji, Maud Salmona, Anaïs Lemoine, Guillaume Ulmann, Julien Calderaro, Brigitte Roche, Nathalie Kapel, Lucie Biard, Etienne Lengline, Jérôme Le Goff, Christophe Rodriguez, Muriel Thomas, Lara Zafrani","doi":"10.1186/s40164-025-00661-4","DOIUrl":"10.1186/s40164-025-00661-4","url":null,"abstract":"<p><strong>Background: </strong>Neutropenic enterocolitis (NE) is a severe digestive complication of chemotherapy, primarily affecting patients with acute myeloid leukemia (AML). We hypothesized that NE is linked to intestinal barrier dysfunction and gut dysbiosis.</p><p><strong>Methods: </strong>Sixty-five AML patients undergoing induction chemotherapy were included in this prospective monocentric cohort. Among them, 26 patients (40%) were diagnosed with NE. Stool samples were subjected to bacterial load quantification (all bacteria quantitative PCR), 16s rRNA metagenomic analysis, and short-chain-fatty-acids quantification. Additionally, fecal calprotectin and human 𝛃-defensin 2 along with plasmatic inflammatory cytokines, and citrulline levels were measured. Human transcriptomic analysis was conducted on samples obtained from anatomical specimens of colectomies of NE patients.</p><p><strong>Results: </strong>Gut microbiota underwent significant alterations after chemotherapy, transitioning from a diverse and balanced enterotype to enterotypes exhibiting a reduced α-diversity, an increased abundance of Enterococcus faecalis, and a decreased abundance of butyrate-producing genera, which correlated with a decreased fecal concentration of butyrate. Simultaneously, post-chemotherapy, plasma citrulline concentrations decreased indicating enterocyte damages. Finally, human transcriptomic analysis found a significant upregulation of the JAK-STAT signaling KEGG pathway in the colons of NE patients encompassing cytokines (IL-6, OSM-OSMR) that play a pivotal role in sustaining local inflammation within the digestive tract.</p><p><strong>Conclusions: </strong>This work reaffirms the significant influence of chemotherapy on the gut microbiota and the integrity of the enterocyte barrier. Severe NE is marked by the development of a local inflammatory response that may be induced by the reduction in butyrate levels.</p><p><strong>Trial registration: </strong>The study was registered on Clinicaltrials.gov (identifier: NCT04438278).</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"74"},"PeriodicalIF":9.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A correlation of ineffective erythropoiesis and dysregulated signaling pathways in myelodysplastic syndromes/neoplasms.","authors":"Junying Wu, Jinqin Liu, Jia Chen, Lin Yang, Fuhui Li, Tiejun Qin, Zefeng Xu, Jing Liu, Jiaxi Zhou, Lihong Shi, Bing Li, Zhijian Xiao","doi":"10.1186/s40164-025-00664-1","DOIUrl":"https://doi.org/10.1186/s40164-025-00664-1","url":null,"abstract":"<p><p>Over 90% of patients with myelodysplastic syndromes/neoplasms (MDS) exhibit anemia at diagnosis, primarily due to ineffective erythropoiesis. This is characterized by abnormal proliferation and differentiation of erythroid cells influenced by signaling pathways including heme synthesis, ferroptosis, senescence and apoptosis. Despite widespread anemia, the specific mechanisms and pathway alterations at different disease stages are not well understood. This study employed the NUP98-HOXD13 (NHD13) transgenic mouse model, which mimicked the erythroid changes observed in MDS patients, to explore these dynamic pathway changes during disease progression. Based on the severity of anemia and changes in mean corpuscular volume (MCV), four time points were selected: 6 weeks (non-anemic), 12 weeks (mild anemia), 16 weeks (obvious anemia) and 20 weeks (severe macrocytic anemia). The findings indicated that a reduction in erythroid-committed progenitors and impaired erythroid maturation were linked to ineffective erythropoiesis. As the disease progressed, signaling pathways dynamically changed. Heme metabolism and ferroptosis pathways were significantly upregulated in the pre-disease and early disease stages, while senescence and cell cycle pathways were activated in the early stage. The prominent roles of apoptosis, pyroptosis and inflammasome signaling pathways were observed in the late stage. Notably, changes in Gpx4 and Ncoa4 expression, along with transmission electron microscopy analysis, suggested that ferroptosis played a critical role in the early stage of the disease. To our knowledge, this is the first report of the signaling pathway dynamics associated with ineffective erythropoiesis during the pathogenesis and progression of MDS, highlighting potential targets for therapeutic intervention at various stages of the disease.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"71"},"PeriodicalIF":9.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Superiority of targeted RNA sequencing for fusion detection and subtype diagnosis in Chinese sarcoma patients: a multicenter study.","authors":"Gu Jin, Dandan Zhao, Baoming Wang, Xuejiao Liu, Quanyu Yang, Zhengchuang Liu, Qiong Yang, Jianhua Zhu, Jie Zhang, Wei Li, Xiaojuan Wang, Chunyang Wang, Tonghui Ma, Jiayong Liu","doi":"10.1186/s40164-025-00663-2","DOIUrl":"https://doi.org/10.1186/s40164-025-00663-2","url":null,"abstract":"<p><p>Sarcomas are rare, heterogeneous mesenchymal malignancies with notably high misdiagnosis rates. Despite sarcoma patients in China representing about one-quarter of the global disease burden, large-scale NGS-based diagnostic studies remain scarce, with limited sample sizes failing to capture the extensive subtype complexity of sarcomas. To address diagnostic gaps, we conducted the largest multicenter study in China involving 788 patients with soft tissue or bone sarcomas. All samples underwent targeted RNA sequencing (Fusioncapture) alongside standard histopathology, immunohistochemistry, and DNA-based next-generation sequencing (NGS). Compared with DNA-NGS, RNA-based profiling clarified ambiguous fusion calls and uncovered numerous additional and clinically relevant events, including 281 fusions not captured by the DNA panel. Notably, 114 recurrent alterations were strongly subtype-associated, and 20 newly identified receptor tyrosine kinase fusions had therapeutic significance, expanding targetable cases from 3.3% to 6.5%. Furthermore, integrated RNA data led to subtype reclassification in 11.9% of patients, including 22% of those initially diagnosed as \"not otherwise specified\". These findings confirm the utility of targeted RNA sequencing for detecting transcriptionally active fusions, refining pathological classifications, and identifying actionable variants in Chinese sarcoma patients. Despite retrospective design and limited orthogonal validation of some fusions, our results strongly support incorporating RNA-based assays into routine clinical workflows. Ultimately, this integrated approach can improve diagnostic precision, guide personalized treatment strategies, and enhance outcomes for sarcoma patients.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"70"},"PeriodicalIF":9.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epstein-Barr virus infection following allogeneic hematopoietic stem cell transplantation in the era of letermovir for cytomegalovirus prophylaxis.","authors":"Jingtao Huang, Jing Zhou, Shixuan Zhang, Ruoxuan Zhang, Zengkai Pan, Luxiang Wang, Chuanhe Jiang, Jiayu Huang, Zilu Zhang, Yanmin Zhao, Yang Cao, Xiaoxia Hu","doi":"10.1186/s40164-025-00665-0","DOIUrl":"https://doi.org/10.1186/s40164-025-00665-0","url":null,"abstract":"<p><p>Letermovir is an antiviral agent that significantly decreases the frequency of cytomegalovirus (CMV) infections following allogeneic hematopoietic stem cell transplantation (allo-HCT); however, its impact on Epstein-Barr virus (EBV) infection remains unclear. This multicenter, retrospective study involved 565 patients aged ≥ 18 years, who underwent allo-HCT between January 2021 and December 2023, with 284 receiving letermovir prophylaxis (letermovir group) and 281 not (control group). Cumulative incidences of clinically significant CMV infection (cs-CMVi), EBV DNAemia, EBV-disease and post-transplant lymphoproliferative disorder (PTLD) were compared between the groups. The 1-year cumulative incidence of EBV DNAemia did not differ significantly between the letermovir and control groups (58.1% vs. 52.7%, P = 0.3). However, letermovir prophylaxis was associated with a significantly higher incidence of PTLD within the first year post-HCT (7.39% vs. 1.80%, P = 0.00059). Multivariate analysis identified letermovir prophylaxis as an independent risk factor for PTLD (HR [95% CI]: 4.619 [1.458-10.278], P = 0.007). Letermovir altered the early reconstitution trajectory after allo-HCT, particularly in CD8⁺ T cells. Our findings emphasized that although letermovir prophylaxis did not increase the risk of EBV DNAemia in allo-HCT recipients, it was associated with a higher incidence of PTLD. Further studies focusing on immune reconstitutiom dynamics are warranted to elucidate the underlying pathophysiology of EBV-PTLD under letermovir pressure.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"72"},"PeriodicalIF":9.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of diagnosis to treatment interval on outcomes in patients with newly diagnosed marginal zone lymphoma - a US multisite study.","authors":"Narendranath Epperla, Geoffrey Shouse, Natalie S Grover, Pallawi Torka, Kaitlin Annunzio, Marcus Watkins, Andrea Anampa-Guzmán, Beth Christian, Colin Thomas, Stefan K Barta, Praveen Ramakrishnan Geethakumari, Reem Karmali, Nancy L Bartlett, Adam J Olszewski","doi":"10.1186/s40164-025-00666-z","DOIUrl":"https://doi.org/10.1186/s40164-025-00666-z","url":null,"abstract":"<p><p>Diagnosis-to-treatment interval (DTI) is an important prognostic factor in patients with newly diagnosed aggressive lymphomas, however the impact of DTI on outcomes in marginal zone lymphoma (MZL) is unknown. In this multicenter retrospective cohort study, we included adult patients with MZL who received first-line immunochemotherapy within 120 days of diagnosis at 10 US medical centers. Patients who received treatment within 60 days from their diagnosis were classified into the short DTI group and those who received treatment beyond 60 days into long DTI group. The primary objective was progression-free survival (PFS), while secondary objectives included overall survival (OS) and cumulative incidence of histologic transformation (HT) between the two groups. Of the 870 patients with newly diagnosed MZL, 177 patients met the inclusion criteria and were included in this analysis. Among these 144 (81%) were in the short DTI group and 33 (19%) in the long DTI group. In the univariable analysis, presence of B symptoms was associated with short DTI and remained significantly associated with short DTI in the multivariable analysis (OR = 11.91, p = 0.017). Short DTI was not associated with a statistically different PFS or OS compared to long DTI in the univariable or in multivariable analysis. The cumulative incidence of HT was not significantly different between the two groups. This is the first study to-date to report on the association of DTI on outcomes in MZL patients. This lack of prognostic utility of DTI in newly diagnosed MZL, in contrast to aggressive B-cell lymphomas, may be intrinsically linked to the underlying disease biology.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"73"},"PeriodicalIF":9.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}