Blood Neoplasia最新文献

英文中文

Blood Neoplasia

Pub Date : 2026-01-01

引用次数: 0

Blood Neoplasia

Pub Date : 2026-01-01

引用次数: 0

Blood Neoplasia

Pub Date : 2026-01-01

引用次数: 0

Addition of anti-CD38 mAb in newly diagnosed multiple myeloma: advancing toward quadruplet induction regimens 在新诊断的多发性骨髓瘤中添加抗cd38单抗：向四联体诱导方案发展

Blood Neoplasia

Pub Date : 2025-12-18 DOI: 10.1016/j.bneo.2025.100189

Yuqi Wang ∗ , Li Zhang ∗ , Dong He ∗ , Huan Chen , Hanzhen Zhang , Youhai Yuan , Cuilian Zhang , Ru Feng , Yongqiang Wei † , Xiaolei Wei †

Abstract

The incorporation of CD38-targeted monoclonal antibodies into induction therapy has improved outcome in patients with newly diagnosed multiple myeloma (NDMM), yet the benefit across risk subgroups remains controversial. We conducted a systematic search of the Cochrane Library, PubMed, Embase, Scopus, and Web of Science databases to identify studies comparing induction regimens with and without anti-CD38 monoclonal antibodies (daratumumab or isatuximab) and assessed the efficacy and safety of anti-CD38–based induction regimens in NDMM. Primary outcomes were minimal residual disease (MRD)-negativity and progression-free survival (PFS). Eleven trials encompassing 5588 patients, including 915 with high-risk multiple myeloma (HRMM), were included. Anti-CD38–containing regimens significantly increased MRD-negativity in both transplant-eligible (TE; pooled odds ratio [OR], 2.32; 95% confidence interval [CI], 1.74-3.11) and transplant-ineligible (TIE; pooled OR, 3.26; 95% CI, 2.20-4.84) patients. Among TE patients, MRD-negativity improved in both HRMM (pooled OR, 2.01; 95% CI, 1.41-2.88) and standard-risk MM (pooled OR, 2.74; 95% CI, 1.99-3.84). Anti-CD38 therapy also significantly prolonged PFS in TE (pooled hazard ratio [HR], 0.52; 95% CI, 0.38-0.69) and TIE NDMM (pooled HR, 0.55; 95% CI, 0.49-0.61), with an overall survival benefit observed in TIE patients. PFS improvement was consistent across cytogenetic risk and clinical subgroups. Grade 3 or 4 infections and hematologic toxicities occurred more frequently with anti-CD38 regimens. In summary, anti-CD38–based induction improves depth of response and PFS across NDMM populations, including high-risk disease, with increased but manageable toxicity.

【摘要】cd38靶向单克隆抗体联合诱导治疗改善了新诊断多发性骨髓瘤（NDMM）患者的预后，但跨风险亚组的获益仍存在争议。我们对Cochrane Library、PubMed、Embase、Scopus和Web of Science数据库进行了系统检索，以确定有和没有抗cd38单克隆抗体（daratumumab或isatuximab）诱导方案的比较研究，并评估了基于抗cd38诱导方案在NDMM中的有效性和安全性。主要结局是最小残留病（MRD）阴性和无进展生存期（PFS）。纳入了11项试验，包括5588例患者，其中915例为高风险多发性骨髓瘤（HRMM）。含有抗cd38的方案显著增加了适合移植（TE；合并优势比[OR]， 2.32； 95%可信区间[CI]， 1.74-3.11）和不适合移植（TIE；合并优势比[OR]， 3.26; 95% CI, 2.20-4.84）患者的mrd阴性反应。在TE患者中，HRMM（合并OR， 2.01; 95% CI, 1.41-2.88）和标准风险MM（合并OR， 2.74; 95% CI, 1.99-3.84）的mrd阴性均有改善。抗cd38治疗也显著延长了TE患者的PFS（合并危险比[HR]， 0.52; 95% CI, 0.38-0.69）和TIE NDMM（合并危险比[HR]， 0.55; 95% CI, 0.49-0.61）， TIE患者的总体生存获益。PFS的改善在细胞遗传风险和临床亚组中是一致的。抗cd38方案更频繁地发生3级或4级感染和血液毒性。总之，基于抗cd38的诱导改善了NDMM人群的反应深度和PFS，包括高风险疾病，毒性增加但可控。

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引用次数: 0

Epidemiology of Erdheim-Chester disease in the United States: a SEER-based analysis 美国厄德海姆-切斯特病的流行病学：基于seer的分析

Blood Neoplasia

Pub Date : 2025-12-15 DOI: 10.1016/j.bneo.2025.100188

Steven Tessier , Jithma P. Abeykoon , Gordon Ruan , N. Nora Bennani , Mithun V. Shah , Karen L. Rech , Aishwarya Ravindran , Jay H. Ryu , Robert Vassallo , Matthew J. Koster , Caroline J. Davidge-Pitts , Lucinda M. Gruber , W. Oliver Tobin , Julio C. Sartori-Valinotti , Talal Hilal , Liuyan Jiang , Muhammad Alhaj Moustafa , Asra Z. Ahmed , Corrie R. Bach , Jason R. Young , Ronald S. Go

引用次数: 0

The LMO2-LDB1-TAL1 complex regulates transcription networks in acute myeloid leukemia LMO2-LDB1-TAL1复合体调控急性髓性白血病的转录网络

Blood Neoplasia

Pub Date : 2025-11-25 DOI: 10.1016/j.bneo.2025.100186

Nicholas Dunham ∗ , Zhenjia Wang ∗ , Yaseswini Neelamraju , Yan Guo , B. Bishal Paudel , Cem Meydan , Jorge A. Gandara , Fady A Abdelmalak , Hao Fan , Joyce Hardwick , Justin H. Layer , Tak Lee , Bernhard Maier , W. Hayes McDonald , Isaani Patnaik , Subhash Prajapati , Franck Rapaport , Caroline Sheridan , Gloria Sheynkman , Paul Zumbo , Francine E. Garrett-Bakelman †

Abstract

Relapsed acute myeloid leukemia (relAML) remains a clinical challenge. We have shown that epigenetic heterogeneity may contribute to transcriptional dysregulation and disease progression in AML, but the specific aberrant transcriptional programs have not been identified. We analyzed molecular profiles from patient-matched diagnostic and relapse AML specimens. A subset of differentially expressed genes (DEG) that were disparate in direction of expression change identified 2 patient subtypes. We predicted that transcriptional regulators (TR) might regulate the expression patterns observed. The expression patterns of the top TR predicted for the disparate genes associated with clinical outcomes. The top TR predicted for the disparate DEG and DEG identified in a patient-derived xenograft model of relAML included members of the LIM domain only 2 - LIM domain binding 1 - TAL BHLH TF1, erythroid differentiation factor (LMO2-LDB1-TAL1) multisubunit complex (LTMC). Analysis of DepMap data identified LMO2-dependent cells with a subset highly expressing TAL1, suggesting coordinated regulation. TAL1 copurified in immunoprecipitation for LMO2 and LDB1 followed by tandem mass spectrometry analysis in HEL and K562 cells, and results from chromatin immunoprecipitation experiments suggest significant co-occupancy of TAL1 and LDB1. Loss-of-function experiments targeting LMO2, LDB1, and TAL1 in AML cell lines associated with reduced cell growth, downregulation of cell cycle genes, and a negative association with gene expression patterns observed in relapsed patients with increased TAL1 expression. Our results from primary AML specimens and functional analyses of AML cell lines supports an essential role for the LTMC in AML. Targeting the complex or downstream effectors could provide novel therapeutic considerations for a subset of patients with AML.

复发性急性髓性白血病（relAML）仍然是一个临床挑战。我们已经表明，表观遗传异质性可能导致AML的转录失调和疾病进展，但具体的异常转录程序尚未确定。我们分析了与患者匹配的诊断性和复发性AML标本的分子谱。差异表达基因（DEG）的一个子集在表达变化方向上完全不同，确定了2种患者亚型。我们预测转录调节因子（TR）可能调节观察到的表达模式。顶端TR的表达模式预测了与临床结果相关的不同基因。在患者来源的relAML异种移植模型中，预测不同DEG和DEG的最高TR包括LIM结构域仅2- LIM结构域结合1-TAL BHLH TF1，红细胞分化因子（LMO2-LDB1-TAL1）多亚单位复合物（LTMC）的成员。DepMap数据分析发现，依赖lmo2的细胞中有一个高表达TAL1的亚群，表明TAL1有协同调节作用。在HEL和K562细胞中，TAL1在LMO2和LDB1的免疫沉淀中共纯化，随后进行串联质谱分析，染色质免疫沉淀实验结果表明TAL1和LDB1显著共占。在AML细胞系中，针对LMO2、LDB1和TAL1的功能丧失实验与细胞生长减少、细胞周期基因下调以及TAL1表达增加的复发患者中观察到的基因表达模式负相关。我们的研究结果来自原发性AML标本和AML细胞系的功能分析，支持LTMC在AML中的重要作用。靶向复杂或下游效应物可能为一部分AML患者提供新的治疗考虑。

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引用次数: 0

SKIDA1 sustains MLL::ENL-expressing hematopoietic progenitors during neonatal stages and promotes B-lineage priming SKIDA1在新生儿期维持MLL:: enl表达的造血祖细胞并促进b谱系启动

Blood Neoplasia

Pub Date : 2025-11-17 DOI: 10.1016/j.bneo.2025.100185

Jonny Mendoza-Castrejon , Wei Yang , Elisabeth Denby , Rohini Muthukumar , Emily B. Casey , Riddhi M. Patel , Sarah K. Tasian , Jeffrey A. Magee

Abstract

Infant leukemias arise as B-cell acute lymphoblastic or acute myeloid leukemia. Most are driven by chromosomal rearrangements of the MLL/KMT2A gene (MLLr) and arise in utero, implying a fetal cell of origin. Fetal and neonatal hematopoietic progenitors have unique transcriptomes and epigenomes, raising the question of whether MLL fusion proteins activate distinct target genes during these early stages of life. In this study, we used a transgenic mouse model of MLL::ENL-driven leukemia to identify Skida1 as a target gene that is more highly induced in fetal and neonatal progenitors than in adult progenitors. SKIDA1 is highly expressed in human MLLr leukemias, and the encoded protein associates with the polycomb repressive complex 2. We show that Skida1 is dispensable for normal hematopoiesis, but it promotes B-cell priming and maintains MLL::ENL-expressing hematopoietic stem cells (HSCs) and multipotent progenitor cells during neonatal development. Conditional deletion of Skida1 has no effect on normal HSC function, yet it impairs B-cell production from neonatal MLL::ENL-expressing HSCs while leaving myeloid leukemogenesis unaffected. Temporally restricted targets of MLL fusion proteins, such as SKIDA1, can therefore tune cell fates at different ages, potentially influencing the types MLLr leukemias that arise at different ages.

婴儿白血病可分为b细胞急性淋巴母细胞白血病和急性髓细胞白血病。大多数是由MLL/KMT2A基因（MLLr）的染色体重排驱动，并在子宫内出现，这意味着胎儿细胞的起源。胎儿和新生儿造血祖细胞具有独特的转录组和表观基因组，这就提出了MLL融合蛋白是否在生命的早期阶段激活不同的靶基因的问题。在这项研究中，我们使用MLL:: enl驱动白血病的转基因小鼠模型来鉴定Skida1作为靶基因，在胎儿和新生儿祖细胞中比在成年祖细胞中更容易被诱导。SKIDA1在人类MLLr白血病中高表达，编码蛋白与多梳抑制复合体2相关。我们发现Skida1在正常造血过程中是不可缺少的，但它在新生儿发育过程中促进b细胞的启动并维持表达MLL:: enl的造血干细胞（hsc）和多能祖细胞。条件性缺失Skida1对正常的HSC功能没有影响，但它会损害新生儿表达MLL:: enl的HSC产生b细胞，而不影响髓系白血病的发生。因此，暂时受限的MLL融合蛋白靶标，如SKIDA1，可以调整不同年龄的细胞命运，潜在地影响不同年龄出现的MLL白血病类型。

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引用次数: 0

Mezigdomide combined with bortezomib disrupts the cell cycle and elicits superior antitumor effects in multiple myeloma 美西多胺联合硼替佐米可破坏细胞周期，在多发性骨髓瘤中产生优越的抗肿瘤效果

Blood Neoplasia

Pub Date : 2025-11-07 DOI: 10.1016/j.bneo.2025.100179

Chad C. Bjorklund , Marta Larrayoz , Jian Kang , Hsiling Chiu , Natasha Shtraizent , Lei Wu , Shirong Li , Chih-Chao Hsu , Junfei Zhao , Michael Amatangelo , Tracy T. Chow , Krista Wollerman , Ram Kumar Singh , Sneha Sridhara , Shailesh Dudhgaonkar , Prakash Subramanyam , Kaushik Ghosh , Paul G. Richardson , Nizar J. Bahlis , Anjan Thakurta , Patrick R. Hagner

Abstract

Triplet regimens that include an immunomodulatory agent, proteasome inhibitor, and dexamethasone are widely used in newly diagnosed and relapsed/refractory (R/R) multiple myeloma (MM). Mezigdomide (MEZI; CC-92480) is a cereblon E3 ubiquitin ligase modulator that is being clinically investigated in combination with bortezomib (BTZ) and low-dose dexamethasone (DEX) for safety and efficacy in pretreated R/RMM. The single-agent mechanism of action (MOA) of MEZI has been defined by the recruitment and degradation of essential MM transcription factors Ikaros and Aiolos, leading to cell autonomous antitumor effects and immune modulation. These effects were confirmed in patients based on pharmacodynamic measurements of Ikaros/Aiolos degradation in biomarker evaluations of immune subsets. However, the MOA of triplet regimens, including that of MEZI/BTZ/DEX remain poorly defined. To better understand the MOA of this triplet combination, we compared the mechanistic contributions of MEZI, BTZ, or DEX alone, or in combination, in preclinical MM models in vitro and in vivo. Additionally, we have compared these results with similar combinations with the immunomodulatory agent pomalidomide (POM). Our studies indicate that the MEZI/BTZ/DEX triplet is superior to all single agents and POM/BTZ/DEX in terms of potency of antiproliferative and proapoptotic activities, substrate degradation depth and kinetics in the presence of BTZ, and in vivo efficacy. We show that the combination of MEZI with BTZ increases cell death through disruption of multiple phases of the cell cycle and this thereby enhances the direct cytotoxic effects of the combination treatment.

摘要免疫调节剂、蛋白酶体抑制剂和地塞米松三联疗法被广泛应用于新诊断和复发/难治性多发性骨髓瘤（MM）。Mezigdomide （MEZI; CC-92480）是一种小脑E3泛素连接酶调节剂，目前正在临床研究与硼替佐米（BTZ）和低剂量地塞米松（DEX）联合用于预处理R/RMM的安全性和有效性。MEZI的单药作用机制（MOA）是通过募集和降解MM必需转录因子Ikaros和Aiolos，导致细胞自主抗肿瘤作用和免疫调节。基于免疫亚群生物标志物评估中Ikaros/Aiolos降解的药效学测量，这些效应在患者中得到了证实。然而，包括MEZI/BTZ/DEX在内的三重方案的MOA仍然定义不清。为了更好地了解这种三联体组合的MOA，我们比较了MEZI， BTZ或DEX单独或联合在体外和体内临床前MM模型中的机制贡献。此外，我们将这些结果与免疫调节剂pomalidomide （POM）的类似组合进行了比较。我们的研究表明，在抗增殖和促凋亡活性、BTZ存在下底物降解深度和动力学以及体内功效方面，MEZI/BTZ/DEX三联体优于所有单一药物和POM/BTZ/DEX。我们发现，MEZI和BTZ联合使用会破坏细胞周期的多个阶段，从而增加细胞死亡，从而增强联合治疗的直接细胞毒性作用。

{"title":"Mezigdomide combined with bortezomib disrupts the cell cycle and elicits superior antitumor effects in multiple myeloma","authors":"Chad C. Bjorklund , Marta Larrayoz , Jian Kang , Hsiling Chiu , Natasha Shtraizent , Lei Wu , Shirong Li , Chih-Chao Hsu , Junfei Zhao , Michael Amatangelo , Tracy T. Chow , Krista Wollerman , Ram Kumar Singh , Sneha Sridhara , Shailesh Dudhgaonkar , Prakash Subramanyam , Kaushik Ghosh , Paul G. Richardson , Nizar J. Bahlis , Anjan Thakurta , Patrick R. Hagner","doi":"10.1016/j.bneo.2025.100179","DOIUrl":"10.1016/j.bneo.2025.100179","url":null,"abstract":"<div><h3>Abstract</h3><div>Triplet regimens that include an immunomodulatory agent, proteasome inhibitor, and dexamethasone are widely used in newly diagnosed and relapsed/refractory (R/R) multiple myeloma (MM). Mezigdomide (MEZI; CC-92480) is a cereblon E3 ubiquitin ligase modulator that is being clinically investigated in combination with bortezomib (BTZ) and low-dose dexamethasone (DEX) for safety and efficacy in pretreated R/RMM. The single-agent mechanism of action (MOA) of MEZI has been defined by the recruitment and degradation of essential MM transcription factors Ikaros and Aiolos, leading to cell autonomous antitumor effects and immune modulation. These effects were confirmed in patients based on pharmacodynamic measurements of Ikaros/Aiolos degradation in biomarker evaluations of immune subsets. However, the MOA of triplet regimens, including that of MEZI/BTZ/DEX remain poorly defined. To better understand the MOA of this triplet combination, we compared the mechanistic contributions of MEZI, BTZ, or DEX alone, or in combination, in preclinical MM models in vitro and in vivo. Additionally, we have compared these results with similar combinations with the immunomodulatory agent pomalidomide (POM). Our studies indicate that the MEZI/BTZ/DEX triplet is superior to all single agents and POM/BTZ/DEX in terms of potency of antiproliferative and proapoptotic activities, substrate degradation depth and kinetics in the presence of BTZ, and in vivo efficacy. We show that the combination of MEZI with BTZ increases cell death through disruption of multiple phases of the cell cycle and this thereby enhances the direct cytotoxic effects of the combination treatment.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"3 1","pages":"Article 100179"},"PeriodicalIF":0.0,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of European LeukemiaNet–guided postremission therapy on outcomes of patients with AML from 2010 to 2022 欧洲白血病网引导的缓解后治疗对2010 - 2022年AML患者预后的影响

Blood Neoplasia

Pub Date : 2025-11-06 DOI: 10.1016/j.bneo.2025.100181

Andrew F. Berdel ∗ , Julian Ronnacker ∗ , Daniela V. Wenge , Lina J. Kolloch , Philipp Berning , Linus Angenendt , Tobias J. Brix , Annette Westermann , Klaus Wethmar , Torsten Kessler , Andrea Kerkhoff , Rolf M. Mesters , Christian Reicherts , Jan-Henrik Mikesch , Wolfgang E. Berdel , Georg Lenz , Christoph Schliemann , Matthias Stelljes

Abstract

The European LeukemiaNet (ELN) classification for acute myeloid leukemia (AML) incorporates cytogenetic and mutational risk profiles of AML to define separate risk groups that correlate with survival outcomes. Recommendations for postremission treatment (PRT) intensity, mainly allogeneic hematopoietic stem cell transplant, are based on these risk groups. In-depth genetically defined cohorts of registries or clinical trials, often reported as retrospective real-world validation cohorts, contain an inherent bias as patients were not treated according to recommendations matching time intervals of the respective ELN classification. We analyzed 662 patients with AML who received intensive induction therapy at our center between 2010 and 2022. Patients were classified according to ELN 2010 if treated between 2010 and 2016, and ELN 2017 if treated between 2017 and 2022. Overall survival (OS) and relapse-free survival (RFS) significantly improved for patients treated between 2017 and 2022 compared with those treated between 2010 and 2016 (4-year OS, 60% vs 40%; 4-year RFS, 54% vs 35%). To eliminate treatment bias, patients treated between 2017 and 2022 were retrospectively reclassified for genetic risk according to ELN 2010 and compared with regularly classified patients treated between 2010 and 2016. The improved outcome was particularly evident for intermediate-risk (IR) patients, whereas favorable and adverse subgroups showed no significant difference. This is, to our knowledge, the first analysis examining the impact of ELN-guided PRT in the context of treatment algorithms applied in the respective ELN time period. We conclude that the shift of risk groups between ELN 2010 and 2017, along with the resulting intensified PRT, contributed to significantly improved survival of patients with AML, particularly those with IR.

摘要：急性髓系白血病（AML）的欧洲白血病网（ELN）分类纳入了AML的细胞遗传学和突变风险概况，以定义与生存结果相关的单独风险组。缓解后治疗（PRT）强度的建议，主要是同种异体造血干细胞移植，是基于这些风险群体。登记或临床试验的深度遗传定义队列，通常被报道为回顾性真实世界验证队列，包含固有的偏倚，因为患者没有根据相应ELN分类的推荐匹配时间间隔进行治疗。我们分析了2010年至2022年间在我们中心接受强化诱导治疗的662例AML患者。在2010年至2016年期间治疗的患者根据ELN 2010进行分类，在2017年至2022年期间治疗的患者根据ELN 2017进行分类。与2010年至2016年治疗的患者相比，2017年至2022年治疗的患者的总生存期（OS）和无复发生存期（RFS）显着提高（4年OS， 60%对40%；4年RFS， 54%对35%）。为了消除治疗偏倚，根据ELN 2010对2017年至2022年治疗的患者进行回顾性遗传风险重新分类，并与2010年至2016年治疗的常规分类患者进行比较。改善的结果对中危（IR）患者尤其明显，而有利亚组和不良亚组没有显着差异。据我们所知，这是第一次分析在各自的ELN时间段内应用的治疗算法中检查ELN引导的PRT的影响。我们得出结论，2010年至2017年ELN期间风险组的转移，以及由此产生的PRT强化，显著提高了AML患者的生存率，特别是那些IR患者。

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引用次数: 0

Ratios of CD8 T lymphocytes to M-MDSCs (CD8MMR) predict prognosis in patients with untreated DLBCL CD8 T淋巴细胞与M-MDSCs的比值（CD8MMR）预测未经治疗的DLBCL患者的预后

Blood Neoplasia

Pub Date : 2025-11-06 DOI: 10.1016/j.bneo.2025.100180

Hao-Yuan Wang , Fu-Chen Yang , Ching-Fen Yang , Chun-Kuang Tsai , Po-Chun Liu , Po-Shen Ko , Yao-Chung Liu , Jyh-Pyng Gau , Jin-Hwang Liu , Po-Min Chen , Nien-Jung Chen

Abstract

CD8 and CD4 T lymphocytes play critical roles in antitumor immunity and are central to immune-based therapies for diffuse large B-cell lymphoma (DLBCL). Conversely, monocytic myeloid-derived suppressor cells (M-MDSCs) promote immunosuppression and tumor progression. This study investigates the prognostic value of the ratios of CD8 and CD4 T lymphocytes to M-MDSCs, referred to as CD8MMR and CD4MMR, in patients with untreated DLBCL. In a prospective observational study, 160 patients newly diagnosed with DLBCL were enrolled and randomized into training (n = 120) and validation (n = 40) cohorts. Circulating immune cells were assessed from fresh peripheral blood using flow cytometry, and cutoff values for CD8MMR and CD4MMR were determined by receiver operating characteristic curve and area under the curve analysis. Patients with high-risk International Prognostic Index (IPI), double-expressor lymphoma, or Epstein-Barr virus–positive DLBCL had significantly lower CD8MMR and CD4MMR. Low CD8MMR (<3.56) or CD4MMR (<3.79) was significantly associated with inferior progression-free survival (PFS) and overall survival (OS). When combining both ratios, patients with high levels of CD8MMR and CD4MMR had the most favorable survival, whereas those with low levels of both had the poorest outcomes; discordant levels corresponded to intermediate survival. Multivariate analysis revealed CD8MMR as an independent predictor of PFS and OS, with greater predictive strength than CD4MMR. Furthermore, CD8MMR stratified survival outcomes across different IPI risk categories and cell-of-origin subtypes, consistently identifying patients with poor prognosis. These findings suggest that CD8MMR is a novel and independent prognostic biomarker in DLBCL, offering additional value for risk stratification in clinical practice.

cd8和CD4 T淋巴细胞在抗肿瘤免疫中发挥关键作用，是弥漫性大b细胞淋巴瘤（DLBCL）免疫治疗的核心。相反，单核细胞髓源性抑制细胞（M-MDSCs）促进免疫抑制和肿瘤进展。本研究探讨了CD8和CD4 T淋巴细胞与M-MDSCs的比值（即CD8MMR和CD4MMR）在未经治疗的DLBCL患者中的预后价值。在一项前瞻性观察研究中，160名新诊断为DLBCL的患者入组并随机分为训练组（n = 120）和验证组（n = 40）。采用流式细胞术检测新鲜外周血循环免疫细胞，通过受试者工作特征曲线和曲线下面积分析确定CD8MMR和CD4MMR的截止值。高风险国际预后指数（IPI）、双表达淋巴瘤或Epstein-Barr病毒阳性DLBCL患者的CD8MMR和CD4MMR显著降低。低CD8MMR （<3.56）或CD4MMR （<3.79）与较差的无进展生存期（PFS）和总生存期（OS）显著相关。当结合这两个比率时，CD8MMR和CD4MMR水平高的患者具有最有利的生存，而两者水平低的患者预后最差；不和谐水平对应于中等生存期。多变量分析显示CD8MMR是PFS和OS的独立预测因子，其预测强度高于CD4MMR。此外，CD8MMR对不同IPI风险类别和细胞来源亚型的生存结果进行了分层，一致地识别出预后不良的患者。这些发现表明，CD8MMR是DLBCL中一种新的、独立的预后生物标志物，在临床实践中为风险分层提供了额外的价值。

{"title":"Ratios of CD8 T lymphocytes to M-MDSCs (CD8MMR) predict prognosis in patients with untreated DLBCL","authors":"Hao-Yuan Wang , Fu-Chen Yang , Ching-Fen Yang , Chun-Kuang Tsai , Po-Chun Liu , Po-Shen Ko , Yao-Chung Liu , Jyh-Pyng Gau , Jin-Hwang Liu , Po-Min Chen , Nien-Jung Chen","doi":"10.1016/j.bneo.2025.100180","DOIUrl":"10.1016/j.bneo.2025.100180","url":null,"abstract":"<div><h3>Abstract</h3><div>CD8 and CD4 T lymphocytes play critical roles in antitumor immunity and are central to immune-based therapies for diffuse large B-cell lymphoma (DLBCL). Conversely, monocytic myeloid-derived suppressor cells (M-MDSCs) promote immunosuppression and tumor progression. This study investigates the prognostic value of the ratios of CD8 and CD4 T lymphocytes to M-MDSCs, referred to as CD8MMR and CD4MMR, in patients with untreated DLBCL. In a prospective observational study, 160 patients newly diagnosed with DLBCL were enrolled and randomized into training (n = 120) and validation (n = 40) cohorts. Circulating immune cells were assessed from fresh peripheral blood using flow cytometry, and cutoff values for CD8MMR and CD4MMR were determined by receiver operating characteristic curve and area under the curve analysis. Patients with high-risk International Prognostic Index (IPI), double-expressor lymphoma, or Epstein-Barr virus–positive DLBCL had significantly lower CD8MMR and CD4MMR. Low CD8MMR (<3.56) or CD4MMR (<3.79) was significantly associated with inferior progression-free survival (PFS) and overall survival (OS). When combining both ratios, patients with high levels of CD8MMR and CD4MMR had the most favorable survival, whereas those with low levels of both had the poorest outcomes; discordant levels corresponded to intermediate survival. Multivariate analysis revealed CD8MMR as an independent predictor of PFS and OS, with greater predictive strength than CD4MMR. Furthermore, CD8MMR stratified survival outcomes across different IPI risk categories and cell-of-origin subtypes, consistently identifying patients with poor prognosis. These findings suggest that CD8MMR is a novel and independent prognostic biomarker in DLBCL, offering additional value for risk stratification in clinical practice.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"3 1","pages":"Article 100180"},"PeriodicalIF":0.0,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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