Hematological Oncology最新文献

{"title":"Gene Expression Profiling in Acute Myeloid Leukemia Patient Subgroups With High and Low Sensitivity Toward SYK Inhibitors","authors":"Marte Karen Brattås,&nbsp;Franziska Görtler,&nbsp;Silje Johansen,&nbsp;Kristin Paulsen Rye,&nbsp;Kimberley Joanne Hatfield,&nbsp;Håkon Reikvam","doi":"10.1002/hon.70058","DOIUrl":"https://doi.org/10.1002/hon.70058","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by the uncontrolled proliferation of myeloid cells, and despite recent treatment advances, patient outcomes remain suboptimal. The cytoplasmic spleen tyrosine kinase (SYK) has emerged as a promising therapeutic target in AML due to its role in promoting leukemic cell survival, proliferation, and chemoresistance. This study investigates in vitro antiproliferative effects of SYK inhibitors on leukemia cells by analyzing 48 primary AML samples treated with five SYK inhibitors: fostamatinib, entospletinib, cerdulatinib, TAK-659, and RO9021. Our findings revealed significant heterogeneity among patients, leading to the identification of two distinct patient sample groups that were identified as having either high or low sensitivity toward SYK inhibitors. Furthermore, gene expression profiling through RNA sequencing of AML patient samples uncovered 97 significantly differentially expressed genes (DEGs) between the two patient groups with high or low in vitro sensitivity toward SYK inhibitors. Pathway enrichment analyses revealed that the high-sensitivity group was enriched in biological processes related to positive gene regulation and significant pathways included cell adhesion molecules and proteoglycans. In contrast, the low-sensitivity group showed enrichment in pathways related to PI3K-Akt signaling and JAK-STAT signaling.</p>\u0000 <p>Gene set enrichment analysis further highlighted that high-sensitivity patient samples were upregulated in pathways associated with oxidative phosphorylation and MYC targets, whereas low-sensitivity patient samples showed enrichment in TGF beta signaling and IL6 JAK STAT3 signaling. These results identify gene expression profile signatures that may predict sensitivity to SYK inhibition and underscore the potential for personalized therapeutic strategies in AML.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of CDA Dynamics on Clinical Outcome of Patients With AML or High-Risk MDS Treated With Nucleoside Analogs","authors":"Erwann Collomb,&nbsp;Laurent Bourguignon,&nbsp;Antoine Tichadou,&nbsp;Pauline Roche,&nbsp;Guillaume Berton,&nbsp;Joseph Ciccolini,&nbsp;Julien Colle,&nbsp;Laure Farnault,&nbsp;Régis Costello,&nbsp;Raphaëlle Fanciullino,&nbsp;Geoffroy Venton","doi":"10.1002/hon.70057","DOIUrl":"https://doi.org/10.1002/hon.70057","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Analysis of Single-Cell and Bulk Transcriptomics Identified Regulatory T-Cell Features as Predictors of Prognosis in Diffuse Large B-Cell Lymphoma","authors":"Yaoli Cui,&nbsp;Ge Hu,&nbsp;Xue Han,&nbsp;Wei Li,&nbsp;Xianhuo Wang,&nbsp;Zhengzi Qian,&nbsp;Lanfang Li,&nbsp;Lihua Qiu,&nbsp;Shiyong Zhou,&nbsp;Huilai Zhang","doi":"10.1002/hon.70050","DOIUrl":"https://doi.org/10.1002/hon.70050","url":null,"abstract":"<div>\u0000 \u0000 <p>Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous malignancy. Advances in transcriptomic and genetic profiling have significantly enhanced our understanding of the disease's intrinsic pathogenesis, uncovering numerous potential therapeutic targets. However, the impact of tumor-infiltrating Regulatory T cells (Tregs) on the prognosis of DLBCL remains controversial. Here, we developed a Treg-associated gene signature by integrating single-cell and bulk transcriptome data to predict the prognosis of DLBCL patients receiving standard immunochemotherapy. In total, 227 Tregs feature genes were identified, six of which were selected for constructing a prognostic signature. DLBCL patients possessing high-risk scores had significantly poorer survival outcomes than those who possess low-risk scores in NCICCR and validation cohorts. Mutations in PIM1, MYD88, DTX1, CARD11, CD79B, ETV6, BCL6, and CDKN2A were predominantly observed in the high-risk group, whereas alterations in TNFRSF14 and DNMT3A were more frequently detected in the low-risk group. Immune infiltration analysis revealed that the high-risk group exhibited an immunosuppressive microenvironment, whereas the low-risk group showed a higher abundance of non-cellular components in the tumor microenvironment (TME). Finally, the Treg features TNFRSF25 and SELL can effectively predict long-term responses to Axicabtagene Ciloleucel (Axi-cel) treatment. In summary, our study developed a prognostic signature consisting of six Treg feature genes by integrating single-cell and bulk transcriptomics to predict clinical outcomes in DLBCL patients. The risk signature was significantly associated with immunological characteristics.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting of PIM Kinases Shows Single Agent Efficacy and Synergizes With BCL2 Inhibitors in Diffuse Large B Cell Lymphoma of the ABC Subtype","authors":"Chiara Tarantelli,&nbsp;Omar Kayali,&nbsp;Elisa Civanelli,&nbsp;Luciano Cascione,&nbsp;Afua Adjeiwaa Mensah,&nbsp;Chiara Folloni,&nbsp;Alberto J. Arribas,&nbsp;Andrea Rinaldi,&nbsp;Vladimir Cmiljanovic,&nbsp;Patrizia Mondello,&nbsp;Francesco Bertoni","doi":"10.1002/hon.70055","DOIUrl":"https://doi.org/10.1002/hon.70055","url":null,"abstract":"<div>\u0000 \u0000 <p>The PIM family of serine/threonine kinases (PIM1, PIM2, and PIM3) are involved in the development of cancer and represent promising therapeutic targets. We investigated the therapeutic potential of targeting PIM kinases in diffuse large B-cell lymphoma (DLBCL), particularly the activated B-cell-like (ABC) subtype, using the pan-PIM inhibitor AZD1208. We demonstrated that PIM1 and PIM2 are more highly expressed in ABC- cells than in germinal center B-cell-like (GCB) -DLBCL cells, and that ABC-DLBCL cell lines are more sensitive to PIM inhibition with AZD1208. Transcriptome analysis of ABC-DLBCL cell lines treated with AZD1208 revealed a downregulation of genes involved in NF-κB signaling, a crucial pathway for ABC-DLBCL. We also explored synergistic drug combinations using a high-throughput screen, which identified BCL2 and glutaminase inhibitors as effective partners for AZD1208, particularly in aggressive ABC-DLBCL and double-hit cell lines. The combination of AZD1208 with the clinically available BCL2 inhibitor venetoclax was synergistic in most DLBCL cell lines, and this combination induced apoptosis and reduced levels of AKT and MCL1 proteins. In conclusion, our findings suggested that AZD1208, especially when combined with BCL2 inhibitors like venetoclax, holds promise as a treatment strategy for aggressive lymphomas. These combinations may enable lower doses of PIM inhibitors, leading to increased tolerability and improved anti-tumor activity in clinical settings. The study also highlighted the potential for targeting PIM kinases in combination with other therapies to overcome drug resistance in DLBCL.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicity and Tolerability of the OEPA/COPDAC Regimen in Children and Adolescents With Hodgkin Lymphoma: A Real-World Experience","authors":"Hala Bekhit,&nbsp;Louay Eldeeb,&nbsp;Emad Moussa,&nbsp;Sarah H. Youssef,&nbsp;Nesreen Ali","doi":"10.1002/hon.70048","DOIUrl":"https://doi.org/10.1002/hon.70048","url":null,"abstract":"<div>\u0000 \u0000 <p>Vincristine, etoposide, prednisone, and doxorubicin (OEPA)/cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDAC) regimen represents a preferred chemotherapy backbone for response-adapted treatment of pediatric Hodgkin Lymphoma (HL). Epidemiological, demographic, and clinical characteristics differ between children with HL from developing and developed countries. Administration of OEPA/COPDAC in low-middle-income countries (LMIC) has been associated with high treatment-related mortality (TRM), hindering its wide adoption. In this comprehensive analysis, we evaluated OEPA/COPDAC-associated adverse events and their impact on treatment delivery in 301 Egyptian patients with pediatric HL aged 2.5–17.9 years. The mean age at presentation was 10.1 years (72% of patients ≤ 13 years) with a male-to-female ratio of 2.6:1. The three treatment groups (TG) were represented. Nodular Sclerosis classic HL (59.8%) represented the most common histopathological subtype. Adverse events were reported during 49.8% of the administered cycles. Eighty-nine and 76.4% of the patients encountered toxicity during OEPA1 and OEPA2 cycles respectively. The frequency of toxicity during COPDAC cycles ranged from 16% to 29.4%. Grade 3/4 decreased neutrophils were the most commonly occurring AE during OEPA cycles (range 71%–85%). Profound neutropenia occurred in 27.9% and 13.8% during OEPA1 and OEPA2 respectively. Profound neutropenia significantly differed across age groups. Treatment-related mortality (TRM) occurred in 1% of the patients. Ninety-eight percent of the scheduled chemotherapy cycles were successfully administered. Treatment modification due to toxicity was required in 9.3% of patients whereas 121 hospital admissions (891 days) were reported. Recurrent toxicity that is, toxicity in &gt; 50% of administered cycles and consequently hospital admission significantly differed across age groups. Our findings support that low TRM is achievable in LMIC centers with adequate infrastructure and treatment capabilities. We additionally provide real-life data on the associated treatment modification and hospital admission.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of VDAC1 Promotes Ferroptosis in Diffuse Large B-Cell Lymphoma","authors":"Chuanming Lin,&nbsp;Liuyan Xin,&nbsp;Shuiling Xie","doi":"10.1002/hon.70054","DOIUrl":"https://doi.org/10.1002/hon.70054","url":null,"abstract":"<div>\u0000 \u0000 <p>Diffuse large B-cell lymphoma (DLBCL) is a prevalent subtype of non-Hodgkin's lymphoma (NHL). Ferroptosis is a novel form of cell death involved in multiple tumor development. However, the relationship between ferroptosis-related genes and DLBCL has not been extensively studied. The GSE95290 dataset was downloaded from the Gene Expression Omnibus (GEO) database and merged with genes associated with ferroptosis to screen differentially expressed genes (DEGs). Hub genes were identified by constructing a protein-protein interaction (PPI) network. The messenger RNA (mRNA) expressions of hub genes were subsequently detected in vitro using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). The impact of voltage dependent anion channel 1 (VDAC1) on the proliferation, apoptosis, and ferroptosis of DLBCL was evaluated using Cell Counting Kit-8, flow cytometry, and relevant ferroptosis assays, respectively. Six highly expressed hub genes were identified, all of which could be used as diagnostic biomarkers for DLBCL. In vitro studies revealed that suppressing VDAC1 expression inhibited DLBCL cell proliferation and promoted apoptosis. Furthermore, knockdown of VDAC1 promoted ferroptosis in DLBCL cells and xenograft tumor models, resulting in elevated levels of malondialdehyde (MDA) and iron and increased protein levels of Acyl-CoA synthetase long-chain family 4 (ACSL4) and cyclooxygenase-2 (COX2). Conversely, glutathione (GSH) and superoxide dismutase (SOD) levels were reduced, accompanied by decreased protein levels of glutathione peroxidase 4 (GPX4) and ferritin heavy chain1 (FTH1). VDAC1 knockdown induces ferroptosis in DLBCL, which provides new insights into the pathogenic mechanisms of DLBCL.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VEGF as a Relapse Marker and an Intensity of Disease Marker in Patients Affected by POEMS Syndrome Treated With Autologous Peripheral Blood Stem Cell Transplantation","authors":"Francesco Autore,&nbsp;Daniele Mannina,&nbsp;Federica Lessi,&nbsp;Eugenio Galli,&nbsp;Stefania Oliva,&nbsp;Daniele Derudas,&nbsp;Claudia Giannotta,&nbsp;Claudia Crippa,&nbsp;Katia Mancuso,&nbsp;Magda Marcatti,&nbsp;Idanna Innocenti,&nbsp;Rita Mazza,&nbsp;Stefania Bramanti,&nbsp;Luca Laurenti","doi":"10.1002/hon.70049","DOIUrl":"https://doi.org/10.1002/hon.70049","url":null,"abstract":"<div>\u0000 \u0000 <p>Overproduction of vascular endothelial growth factor (VEGF) seems to contribute to the pathogenesis, still unclear, of POEMS Syndrome. Our study retrospectively reviewed the clinical and VEGF data from a multicenter Italian cohort of patients affected by POEMS syndrome who underwent to autologous peripheral blood stem cell transplantation (aPBSCT) in order to find an impact on clinical improvement or outcome. Patients with VEGF levels higher than 758 pg/mL were at higher risk of relapse, with sensible difference in PFS (<i>p</i> = 0.007). VEGF could be used as a marker of relapse and as a marker of disease intensity in patients with POEMS.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote Monitoring of CAR T-Cell Treated Patients by a Specialized Nurse to Detect and Manage Late Complications: Report of the CARAMA Program","authors":"Fanny Colin,&nbsp;Adeline Bellec,&nbsp;Laetitia Le Bars,&nbsp;Magali Granger,&nbsp;Leslie Lucas,&nbsp;Tiphaine Ricard,&nbsp;Sophie de Guibert,&nbsp;Guillaume Manson,&nbsp;Faustine Lhomme,&nbsp;Tony Marchand,&nbsp;Jean-Baptiste Méar,&nbsp;Martine Escoffre,&nbsp;Olivier Decaux,&nbsp;Thierry Lamy,&nbsp;Roch Houot,&nbsp;Aline Moignet","doi":"10.1002/hon.70052","DOIUrl":"https://doi.org/10.1002/hon.70052","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Associations of Gut Microbiota Species With Lymphoma: A Two-Sample Mendelian Randomization Study","authors":"Mei Li,&nbsp;Li Wang,&nbsp;ZiYe Peng,&nbsp;Lian Jiang,&nbsp;YiWei Yan,&nbsp;YaFei Xia,&nbsp;Yao Wang,&nbsp;LiYing Guo,&nbsp;Jing Miao,&nbsp;YuHong Bian","doi":"10.1002/hon.70046","DOIUrl":"https://doi.org/10.1002/hon.70046","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aims to focus on GM at species level, exploring the causal associations with different kinds of lymphoma to provide some information on potential intervention directions in lymphoma. Data of GM taxa were extracted from the genome-wide association study conducted by the MiBioGen and Dutch Microbiome Project (DMP), and those of lymphomas were obtained from the FinnGen consortium. Inverse variance weighted (IVW) method and Bonferroni multiple correction were utilized to assess the causal associations of GM species with different kinds of lymphoma. The effect size was expressed by odds ratios (ORs) with 95% confidence intervals (CIs). Reverse causal association analysis has also been performed. Additionally, scatter plots and leave-one-out test were conducted for sensitivity analysis. After correction, the IVW estimates suggested that elevated relative abundance of species <i>Faecalibacterium_prausnitzii</i> had a negatively causal association with increased odds of Hodgkin's lymphoma (HL) (OR = 0.584, 95% CI: 0.516–0.662). Relative abundance of species <i>Gordonibacter_pamelaeae</i>, <i>Holdemania_filiformis</i>, <i>Sutterella_wadsworthensis</i> and <i>Coprococcus_sp_ART55_1</i> was negatively associated with follicular lymphoma (FL) odds, whereas that of species <i>Bifidobacterium_catenulatum</i> and <i>Coprococcus_comes</i> were positively associated with FL odds (all <i>p</i> &lt; 0.05). Relative abundance of species <i>Akkermansia_muciniphila</i> and <i>Coprococcus_sp_ART55_1</i> had a negatively causal association with non-follicular lymphoma (NFL) odds, respectively, while that of <i>Bacteroides_uniformis</i> had a positive one (all <i>p</i> &lt; 0.05). Relative abundance of species <i>Flavonifractor_plautii</i> was negatively linked to diffuse large B-cell lymphoma (DLBCL) risk (OR = 0.471, 95% CI: 0.344–0.645). Relative abundance of species <i>Eggerthella_unclassified</i> was positively associated with T/NK cell lymphoma (TNK) risk while that of <i>Ruminococcus_lactaris</i> was negatively associated with TNK risk (all <i>p</i> &lt; 0.05). Elevated relative abundance of <i>Parabacteroides_unclassified</i> was associated with higher risk of non-Hodgkin's lymphoma (NHL) (OR = 1.955, 95% CI: 1.654–2.312). The relative abundance of species <i>Holdemania_filiformis</i> was negatively associated with mantle cell lymphoma (MCL) risk (OR = 0.637, 95% CI: 0.544–0.746). The relative abundance of species <i>Rothia_mucilaginosa</i> and <i>Lachnospiraceae_bacterium_3_1_46FAA</i> had positively causal association with marginal zone lymphoma (MZL) risk, while that of species <i>Alistipes_senegalensis</i> had a negative one (all <i>p</i> &lt; 0.05). This study identified 16 GM species that have potential causal associations with different kinds of lymphoma, which provided some new idea for further exploration on prevention and treatment targets in lymphoma.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatments and Outcomes of Newly Diagnosed CD5-Positive Diffuse Large B-Cell Lymphoma: A Multi-Institutional Observational Study","authors":"Yuma Nato,&nbsp;Kana Miyazaki,&nbsp;Dai Maruyama,&nbsp;Hiroyuki Takahashi,&nbsp;Kazutaka Sunami,&nbsp;Satsuki Murakami,&nbsp;Eiju Negoro,&nbsp;Yuri Miyazawa,&nbsp;Ilseung Choi,&nbsp;Takahiro Okada,&nbsp;Nobuyuki Takayama,&nbsp;Naoto Tomita,&nbsp;Shuji Momose,&nbsp;Yuto Kaneda,&nbsp;Masahiro Yoshida,&nbsp;Hiroshi Gomyo,&nbsp;Kohtaro Toyama,&nbsp;Momoko Nishikori,&nbsp;Akio Saito,&nbsp;Junji Hiraga,&nbsp;Taro Masunari,&nbsp;Naoki Takahashi,&nbsp;Junya Makiyama,&nbsp;Tomotaka Suzuki,&nbsp;Hiroko Tsunemine,&nbsp;Jun Takizawa,&nbsp;Takeharu Kato,&nbsp;Yasufumi Masaki,&nbsp;Noriko Fukuhara,&nbsp;Masataka Okamoto,&nbsp;Isao Tawara,&nbsp;Naoko Asano,&nbsp;Koichi Ohshima,&nbsp;Koji Izutsu,&nbsp;Koji Kato,&nbsp;Ritsuro Suzuki,&nbsp;Motoko Yamaguchi","doi":"10.1002/hon.70047","DOIUrl":"https://doi.org/10.1002/hon.70047","url":null,"abstract":"<p>CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by a poor prognosis and frequent central nervous system (CNS) relapse. Sandwich therapy comprising dose-adjusted (DA)-EPOCH-R (etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, and rituximab) and high-dose methotrexate (HD-MTX) (DA-EPOCH-R/HD-MTX) showed excellent efficacy and manageable safety in a phase II study of patients diagnosed with stage II–IV CD5+ DLBCL. To validate the results of that study and elucidate the current state of treatment for CD5+ DLBCL, we retrospectively analyzed the outcomes of patients with CD5+ DLBCL diagnosed between 2016 and 2021 who received anthracycline-containing chemotherapy with rituximab. Among the 346 patients evaluated, 62 (18%) received DA-EPOCH-R/HD-MTX. The median follow-up time was 43 months. In 55 patients with stage II–IV disease treated with DA-EPOCH-R/HD-MTX, the 2-year overall survival (OS), progression-free survival, and cumulative incidence of CNS relapse were 87% (95% CI, 73%–94%), 76% (95% CI, 61%–86%), and 7.3% (95% CI, 2.4%–16%), respectively. There were no treatment-related deaths. Febrile neutropenia occurred in 18 (33%) patients. Multivariate analysis of the 346 patients identified elevated serum lactate dehydrogenase levels, multiple extranodal involvement, no intrathecal MTX (IT-MTX), and no DA-EPOCH-R/HD-MTX as independent risk factors for OS. Only one CNS relapse event was observed in 28 patients who received both HD-MTX and IT-MTX. Our study provides real-world data on the treatments and outcomes of a large number of patients. The favorable survival and manageable toxicity of DA-EPOCH-R/HD-MTX have been validated in clinical settings. The use of HD-MTX and IT-MTX might be effective for preventing CNS relapse in patients with CD5+ DLBCL.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}