Leukemia research最新文献_第2页

The increase in the expression of circRNAs may contributes to a poor prognosis in acute myeloid leukemia: A systematic review and meta-analysis 环状rna表达的增加可能导致急性髓系白血病预后不良：一项系统综述和荟萃分析。

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-01-01 DOI: 10.1016/j.leukres.2024.107639

Meng Li , Shiming Zhang , Junfan Wei , Mengfei Liu , Bohao Zhang , Shen Li , Yue Xiao , Yuandong Yu , Ruipeng Song

Objective

The primary methods for defining the prognostic risk of AML patients are cytogenetic and molecular analysis at the time of diagnosis. However, the prognosis of intermediate-risk patients is still not well assessed for biomarkers. The main objective of this meta-analysis is to evaluate the relationship between circRNAs and AML prognosis, to provide a theoretical basis for finding effective prognostic indicators in intermediate-risk patients, and to provide an important scientific basis for the development or revision of WHO practice guidelines and ELN risk classification, and to highlight the importance of continuing to focus on and evaluate the prognostic impact of circRNAs on AML in future studies.

Methods

We performed a comprehensive literature search across PubMed, the Cochrane Library, and Web of Science databases for studies published up to September 15, 2024. Articles were selected based on inclusion criteria. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of studies. The outcome measure of overall survival (OS) was used, and hazard ratios (HR) and 95 % confidence intervals (CI) were pooled to estimate the relationship between circRNA expression and prognosis in AML using STATA 17.0 software.

Results

A total of 13 studies involving 1401 AML patients were included. The studies showed a significantly increased hazard ratio (HR) of upregulated CircRNA expression for OS (HR=1.87, 95 % CI=1.51–2.32, P < 0.001). The results of subgroups analysis showed a significant increase in the hazard ratio (HR) for upregulation of CircRNA expression in EFS and circ_0012152（HR= 1.66, 95 % CI= 1.19–2.32, P < 0.005 and HR= 2.26,95 % CI= 1.27–4.00, P < 0.005), respectively. No significant heterogeneity or publication bias was detected.

Conclusion

Upregulated circRNA expression is significantly associated with poor prognosis in AML patients and may serve as a prognostic marker for AML.

目的：确定AML患者预后风险的主要方法是在诊断时进行细胞遗传学和分子分析。然而，中危患者的预后仍然没有很好的生物标志物评估。本荟萃分析的主要目的是评估circRNAs与AML预后的关系，为中危险患者寻找有效的预后指标提供理论依据，为WHO实践指南和ELN风险分类的制定或修订提供重要的科学依据，并强调在未来的研究中继续关注和评估circRNAs对AML预后的影响的重要性。方法：我们在PubMed、Cochrane图书馆和Web of Science数据库中进行了全面的文献检索，检索截止到2024年9月15日发表的研究。根据纳入标准选择文章。采用纽卡斯尔-渥太华量表（NOS）评价研究质量。使用总生存期（OS）的结局指标，并使用STATA 17.0软件合并风险比（HR）和95% %置信区间（CI）来估计AML中circRNA表达与预后之间的关系。结果：共纳入13项研究，涉及1401例AML患者。研究显示，CircRNA表达上调对OS的风险比（HR）显著增加（HR=1.87, 95 % CI=1.51-2.32, P ）。结论：CircRNA表达上调与AML患者预后不良显著相关，可作为AML的预后标志物。

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引用次数: 0

Immunological aspects of HTLV-1 persistence; for the prevention and treatment of Adult T-cell leukaemia-lymphoma (ATL) HTLV-1持久性的免疫学方面；用于预防和治疗成人t细胞白血病淋巴瘤（ATL）。

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-01-01 DOI: 10.1016/j.leukres.2024.107635

Devon A. Weterings , Aileen G. Rowan , Lucy B. Cook

Human T-cell leukaemia virus type-1 (HTLV-1) causes the highly aggressive malignancy adult T-cell leukaemia-lymphoma (ATL) in approximately 5 % of chronically infected carriers. HTLV-1 persists in the host by enhancing survival of infected-T-cells despite the presence of a strong immune response. Therefore, asymptomatic HTLV-1 carriers have a lifelong balance between infected cell proliferation and the host antiviral immune response. However, this immunological balance is lost in patients with ATL. Reliable treatment options are lacking and there is urgent need for new treatment strategies to improve the dismal prognosis of ATL. In this review, we present a summary of the current knowledge on the immunological aspects of HTLV-1 persistence and the immune alterations observed in ATL, and discuss how the recent emerging advances in adoptive immunotherapy may offer a prevention and treatment option for ATL.

人类t细胞白血病病毒1型（HTLV-1）在大约5 %的慢性感染携带者中引起高度侵袭性恶性成人t细胞白血病淋巴瘤（ATL）。尽管存在强烈的免疫反应，HTLV-1通过增强被感染t细胞的存活而在宿主中持续存在。因此，无症状HTLV-1携带者在感染细胞增殖和宿主抗病毒免疫应答之间存在终身平衡。然而，ATL患者失去了这种免疫平衡。目前缺乏可靠的治疗方案，迫切需要新的治疗策略来改善ATL的预后。在这篇综述中，我们总结了目前关于HTLV-1持久性和ATL中观察到的免疫改变的免疫学方面的知识，并讨论了最近在过继性免疫治疗方面的新进展如何为ATL提供预防和治疗选择。

引用次数: 0

Recent progress in pathological understanding of adult T-cell leukemia/lymphoma in the new classification era 新分类时代成人T细胞白血病/淋巴瘤病理学认识的最新进展。

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-01-01 DOI: 10.1016/j.leukres.2024.107634

Kennosuke Karube , Shugo Sakihama , Mitsuyoshi Takatori , Kazuho Morichika , Tomoko Tamaki , Naoki Wada , Takuya Fukushima

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by Human T-cell leukemia virus type 1 (HTLV-1) infection. Although the 5th Edition of the WHO classification (WHO-5) did not make drastic changes regarding the disease concept of ATLL from the revised 4th Edition of the WHO classification (WHO-4R), WHO-5 newly introduced the essential and desirable diagnostic criteria, namely, "neoplastic lymphoid cell proliferation with mature T-cell phenotype; proven HTLV-1 carriership" and "identification of monoclonal integration of HTLV-1", respectively. To satisfy the desirable criteria, a new diagnostic method using a combination of HBZ-ISH and tax-PCR was introduced for the identification of the HTLV-1 in addition to the conventionally used Southern blot hybridization, especially in the case when only FFPE specimens are available. Morphologically, pleomorphic- and anaplastic large cell-type, account for most cases, while minor variants, ATLL with dermatopathic reaction, angioimmunoblastic T-cell lymphoma-like variant, and classic Hodgkin lymphoma-like variant, should also be noted as diagnostic pitfalls. Phenotypically, about 80 % of ATLL cases show a typical phenotype of CD3 + CD4 +CD25 +CCR4 + , while about 10 % show atypical phenotypes such as T follicular helper cell-like one. Many genetic abnormalities, mainly associated with the TCR signaling pathway, are observed, and most are more frequent in the aggressive type than in the indolent type, except for STAT3, indicating the heterogeneous pathogenic process of ATLL. In this review, we present the latest findings on molecular pathogenesis and histopathological findings of ATLL in the era of the new classification of lymphomas, serving as a basis for future research and classification.

成人t细胞白血病/淋巴瘤（ATLL）是一种由人t细胞白血病病毒1型（HTLV-1）感染引起的外周t细胞淋巴瘤。尽管与修订后的WHO分类第4版（WHO- 4r）相比，第5版（WHO-5）对ATLL的疾病概念没有重大改变，但WHO-5新引入了必要和理想的诊断标准，即“具有成熟t细胞表型的肿瘤性淋巴样细胞增殖；分别为“证实HTLV-1载体”和“HTLV-1单克隆整合的鉴定”。为了满足期望的标准，除了常规使用的Southern blot杂交之外，还引入了一种新的诊断方法，使用HBZ-ISH和tax-PCR相结合来鉴定HTLV-1，特别是在只有FFPE标本的情况下。形态学上，多形性和间变性大细胞型占大多数病例，而较小的变异，如伴有皮肤病反应的ATLL，血管免疫母细胞t细胞淋巴瘤样变异和经典霍奇金淋巴瘤样变异，也应作为诊断缺陷予以注意。表型上，约80 %的ATLL病例表现为典型的CD3 + CD4 +CD25 +CCR4 + ，而约10 %的ATLL病例表现为非典型表型，如T滤泡辅助细胞样表型。观察到许多遗传异常，主要与TCR信号通路相关，除STAT3外，大多数在侵袭型中比惰性型更常见，表明ATLL的致病过程具有异质性。本文综述了在淋巴瘤新分类时代ATLL的分子发病机制和组织病理学的最新发现，为今后的研究和分类提供依据。

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引用次数: 0

Combination therapy involving azacitidine for acute myeloid leukemia patients ineligible for intensive chemotherapy 阿扎胞苷联合治疗急性髓系白血病患者不适合强化化疗。

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-01-01 DOI: 10.1016/j.leukres.2024.107638

Juan Li , Shuying Fu , Chunmei Ye , Jun Li

Acute myeloid leukemia (AML) is a complex hematological malignancy predominantly affecting the elderly, with a median diagnosis age of 68 years. Despite advances in treatment, elderly AML patients face suboptimal survival outcomes, with an estimated 5-year survival rate below 20 %. Epigenetic dysregulation, notably DNA methylation, is a key factor in the progression of myelodysplastic syndromes (MDS) to AML. This review examines various combination regimens involving azacitidine (AZA), including those with lenalidomide, histone deacetylase inhibitors (HDACi), kinase inhibitors, metabolic enzyme inhibitors, monoclonal antibodies, immune checkpoint inhibitors, and anti-apoptotic protein inhibitors. Notable among these are the combinations with venetoclax, which has demonstrated remarkable efficacy in phase III trials, and the emerging IDH inhibitors ivosidenib and enasidenib, which have shown significant clinical benefits in patients with IDH mutations. While combination therapies with AZA hold great promise, challenges persist, including translating in vitro synergies to in vivo efficacy and identifying optimal regimens for specific patient populations. Cumulative toxicities may also offset clinical benefits, necessitating rigorous clinical trial design. Future research must focus on refining combination strategies, optimizing dosages and sequences, and thoroughly evaluating therapeutic efficacy and safety to advance the treatment of AML and improve patient outcomes.

急性髓性白血病（AML）是一种复杂的血液系统恶性肿瘤，主要影响老年人，中位诊断年龄为68岁。尽管治疗取得了进展，但老年AML患者面临着次优的生存结果，估计5年生存率低于20% %。表观遗传失调，特别是DNA甲基化，是骨髓增生异常综合征（MDS）发展为AML的关键因素。本文综述了阿扎胞苷（AZA）的各种联合治疗方案，包括来那度胺、组蛋白去乙酰化酶抑制剂（HDACi）、激酶抑制剂、代谢酶抑制剂、单克隆抗体、免疫检查点抑制剂和抗凋亡蛋白抑制剂。其中值得注意的是与venetoclax联合使用，在III期试验中显示出显着的疗效，以及新出现的IDH抑制剂ivosidenib和enasidenib，它们在IDH突变患者中显示出显着的临床益处。虽然与AZA联合治疗有很大的希望，但挑战仍然存在，包括将体外协同作用转化为体内疗效，并为特定患者群体确定最佳方案。累积毒性也可能抵消临床益处，因此需要严格的临床试验设计。未来的研究必须专注于改进联合策略，优化剂量和序列，并彻底评估治疗疗效和安全性，以推进AML的治疗并改善患者的预后。

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引用次数: 0

Predictive modeling of outcomes in acute leukemia patients undergoing allogeneic hematopoietic stem cell transplantation using machine learning techniques 利用机器学习技术为接受异基因造血干细胞移植的急性白血病患者建立预后模型

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-11-20 DOI: 10.1016/j.leukres.2024.107619

Maedeh Rouzbahani , Seyed Amirhossein Mousavi , Ghasem Hajianfar , Ali Ghanaati , Mohammad Vaezi , Ardeshir Ghavamzadeh , Maryam Barkhordar

Background

Leukemia necessitates continuous research for effective therapeutic techniques. Acute leukemia (AL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) focus on key outcomes such as overall survival (OS), relapse, and graft-versus-host disease (GVHD).

Objective

This study aims to evaluate the capability of machine learning (ML) models in predicting OS, relapse, and GVHD in AL patients post-allo-HSCT.

Methods

Clinical data from 1243 AL patients, with 10 years of follow-up, was utilized to develop 28 ML models. These models incorporated four feature selection methods and seven ML algorithms. Model performance was assessed using the concordance index (c-index) with multivariate analysis.

Results

The multivariate model analysis showed the best FS/ML combinations were UCI_GLMN, IBMA_GLMN and IBMA_CB for OS, UCI_ST, UCI_RSF, UCI GLMB, UCI_GB, UCI_CB, MI_GLMN, IBMA_ST and IBMA GB for relapse, IBMA_GB for aGVHD and Boruta_GB for cGVHD (all p values < 0.0001, mean C-indices in 0.61–0.68)).

Conclusion

ML techniques, when combined with clinical variables, demonstrate high accuracy in predicting OS, relapse, and GVHD in AL patients.

背景白血病需要不断研究有效的治疗技术。本研究旨在评估机器学习（ML）模型预测异体造血干细胞移植（allo-HSCT）后急性白血病（AL）患者的OS、复发和GVHD（移植物抗宿主疾病）等关键结果的能力。方法利用1243名AL患者10年随访的临床数据开发了28个ML模型。这些模型采用了四种特征选择方法和七种 ML 算法。使用多变量分析的一致性指数（c-index）评估模型的性能。结果多变量模型分析表明，最佳FS/ML组合是：UCI_GLMN、IBMA_GLMN和IBMA_CB用于OS，UCI_ST、UCI_RSF、UCI GLMB、UCI_GB、UCI_CB、MI_GLMN、IBMA_ST和IBMA GB用于复发，IBMA_GB用于aGVHD，Boruta_GB用于cGVHD（所有P值均为0.0001，平均C指数在0.61-0.68之间）。结论ML技术与临床变量相结合，在预测AL患者的OS、复发和GVHD方面表现出很高的准确性。

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引用次数: 0

Real-world impact of luspatercept on red blood cell transfusions among patients with myelodysplastic syndromes: A United States healthcare claims database study Luspatercept 对骨髓增生异常综合征患者输注红细胞的实际影响：美国医疗索赔数据库研究

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-11-17 DOI: 10.1016/j.leukres.2024.107624

Leslie A. Andritsos , Ali McBride , Derek Tang , Victoria Barghout , Enrico Zanardo , Rui Song , Lynn Huynh , Mihran Yenikomshian , Adeola Y. Makinde , Christina Hughes , Kirollos S. Hanna , Kashyap Patel

Myelodysplastic syndromes (MDS) are associated with anemia and the need for blood transfusions. In clinical trials, luspatercept reduced transfusion dependency among patients with lower-risk MDS. This United States (US) study describes real-world clinical outcomes pre- and post-luspatercept initiation among patients with MDS. Symphony Health Integrated Dataverse claims data (August 1, 2010−December 29, 2022) were used to identify patients with MDS treated with luspatercept (first luspatercept claim = index date). Transfusion-dependent (TD) or non-TD (NTD) patients at baseline were described as 8-week transfusion-independent (TI) or as maintaining NTD, respectively, if they had no transfusion for 8 weeks in the 6 months post-index (similarly for 12, 16, and 24 weeks). Transfusion status was measured overall and among patients who were baseline NTD, TD, TD and exposed to erythropoiesis-stimulating agents (ESA) (TD+ESA-exposed), MDS with ring sideroblasts (RS) (MDS-RS), and MDS-non-RS. MDS-related treatments were measured pre- and post-index. Among the 871 patients who received luspatercept (mean age: 74.7 years), 87.4 % achieved 8-week TI/maintained NTD within 6 months post-index, 64.9 % of patients did not receive additional MDS-related treatments post-luspatercept initiation (median follow-up: 14.8 months), 98.5 % of baseline NTD patients maintained 8-week NTD 6 months post-luspatercept initiation, and 88.6 % did not receive a transfusion for 24 weeks. Baseline TD (64.2 %) and TD+ESA-exposed (64.2 %) patients achieved 8-week TI 6 months post-luspatercept initiation. Eight-week TI proportions were similar between MDS-RS (89.8 %) and MDS-non-RS (84.8 %) subgroups. These findings corroborate clinical trial data by showing the high effectiveness of luspatercept among real-world patients with MDS in the US.

骨髓增生异常综合征（MDS）与贫血和输血需求有关。在临床试验中，Luspatercept降低了低风险MDS患者的输血依赖性。这项美国研究描述了 MDS 患者在开始使用 luspatercept 前后的实际临床结果。Symphony Health Integrated Dataverse理赔数据（2010年8月1日-2022年12月29日）被用于识别接受鲁帕特罗治疗的MDS患者（首次鲁帕特罗理赔=索引日期）。如果基线时的输血依赖（TD）或非输血依赖（NTD）患者在索引后的 6 个月内 8 周（12、16 和 24 周类似）没有输血，则将其分别描述为 8 周输血无关（TI）或维持 NTD。输血状态的测量对象包括整体患者以及基线 NTD、TD、TD 并暴露于红细胞生成刺激剂（ESA）（TD+ESA-exposed）、MDS 伴有环形红细胞（RS）（MDS-RS）和 MDS 非 RS 患者。对指数前后的 MDS 相关治疗进行了测量。在接受鲁帕特罗治疗的871名患者中（平均年龄：74.7岁），87.4%的患者在指标发布后6个月内达到8周TI/维持NTD，64.9%的患者在鲁帕特罗治疗后未接受额外的MDS相关治疗（中位随访时间：14.8个月），98.5%的基线NTD患者在鲁帕特罗治疗后6个月内维持8周NTD，88.6%的患者在24周内未接受输血。基线TD（64.2%）和TD+ESA暴露（64.2%）患者在开始接受Luspatercept治疗6个月后实现了8周TI。MDS-RS亚组（89.8%）和MDS-非RS亚组（84.8%）的8周TI比例相似。这些研究结果证实了临床试验数据，显示了luspatercept在美国MDS实际患者中的高度有效性。

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引用次数: 0

Exploring the impact of methylation aging on acute myeloid leukemia: Insights from the aging clock 探索甲基化老化对急性髓性白血病的影响：老化时钟的启示

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-11-15 DOI: 10.1016/j.leukres.2024.107620

Jin-Young Kim , Karthikeyan A. Vijayakumar , Gwang-Won Cho

Acute myeloid leukemia (AML) is more commonly diagnosed in adults. Though there are considerable knowledge about the relationship between adult leukemia and aging, it is rarely studies in children as the occurrence of the disease is rare. Additionally, adult and pediatric AML are known to have different etiology. Studies show that in adult AML, methylation aging is accelerated compared to healthy people. However, this association has not been extensively studied in pediatric AML. To investigate potential correlations between pediatric AML and aging, we analyzed methylation aging clock models that leverage DNA methylation patterns and predict epigenetic age. By established knowledge, we observed that the predicted epigenetic age in adult AML cases exceeds the actual chronological age. Similarly, we found that predicted epigenetic age in pediatric AML cases was also higher than chronological age. In addition, we observed significant changes in the CpG probes of the Epi clock, and these changes were observed to be extensive hypomethylation. Based on this, we found that the Epi clock can recognize changes specific to AML. These findings may have implications for strategies to address aging and quality of life after treatment in pediatric AML patients.

急性髓性白血病（AML）通常在成人中确诊。尽管人们对成人白血病与衰老之间的关系有相当多的了解，但很少对儿童进行研究，因为这种疾病很少发生。此外，已知成人和儿童急性髓细胞白血病的病因不同。研究表明，与健康人相比，成人急性髓细胞白血病患者的甲基化老化速度加快。然而，这种关联在小儿急性髓细胞性白血病中尚未得到广泛研究。为了研究小儿急性髓细胞性白血病与衰老之间的潜在关联，我们分析了利用 DNA 甲基化模式预测表观遗传年龄的甲基化衰老时钟模型。根据已有的知识，我们观察到成人急性髓细胞性白血病病例的预测表观遗传年龄超过了实际年龄。同样，我们发现小儿急性髓细胞性白血病病例的预测表观遗传年龄也高于实际年龄。此外，我们还观察到 Epi 时钟的 CpG 探针发生了显著变化，而且这些变化被观察到是广泛的低甲基化。在此基础上，我们发现 Epi 时钟可以识别急性髓细胞性白血病的特异性变化。这些发现可能对解决儿科急性髓细胞性白血病患者治疗后的衰老和生活质量问题的策略具有重要意义。

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引用次数: 0

NAP1L5 promotes epithelial–mesenchymal transition by regulating PEG10 expression in acute myeloid leukaemia NAP1L5 通过调节急性髓性白血病中 PEG10 的表达促进上皮-间质转化。

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-11-13 DOI: 10.1016/j.leukres.2024.107623

Huan Wu , Hang Luo , Meng Wang , YuQing Du , Jiajia Li

Acute myeloid leukaemia (AML) is a haematological malignancy that poses a serious threat to human health. Studies have shown that the expression of NAP1L5 is elevated in patients with AML; however, the specific molecular mechanism remains unknown. Therefore, in this study, we aimed to investigate the pathogenic mechanisms of NAP1L5 in AML. The expression level of NAP1L5 was increased in AML, and the upregulation of NAP1L5 was related to tumour growth and epithelial–mesenchymal transition. Furthermore, PEG10 is a downstream regulatory factor of NAP1L5, and its overexpression promotes tumour growth and epithelial–mesenchymal transition. More importantly, the loss of PEG10 inhibited the negative effects induced by NAP1L5 overexpression. Our results suggest that NAP1L5 is a novel therapeutic target for AML treatment.

急性髓性白血病（AML）是一种严重威胁人类健康的血液恶性肿瘤。研究表明，NAP1L5 在急性髓性白血病患者中表达升高，但具体的分子机制仍不清楚。因此，本研究旨在探讨 NAP1L5 在 AML 中的致病机制。NAP1L5在AML中的表达水平升高，NAP1L5的上调与肿瘤生长和上皮-间质转化有关。此外，PEG10是NAP1L5的下游调控因子，其过度表达会促进肿瘤生长和上皮-间质转化。更重要的是，PEG10的缺失抑制了NAP1L5过表达引起的负面影响。我们的研究结果表明，NAP1L5是治疗急性髓细胞性白血病的一个新的治疗靶点。

引用次数: 0

RCHOP plus BTK inhibitor improves clinical outcomes in double expressor diffuse large B-cell lymphoma, unlike RCHOP plus lenalidomide 与RCHOP加来那度胺不同，RCHOP加BTK抑制剂可改善双表达弥漫大B细胞淋巴瘤的临床疗效。

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-11-09 DOI: 10.1016/j.leukres.2024.107622

Demei Feng, Shenrui Bai, Dong Liang, Xiaoqin Chen, Zhongjun Xia, Yang Liang, Hua Wang

Background

Double-expressor diffuse large B-cell lymphoma (DE-DLBCL) has a poor prognosis, and optimal treatment strategies remain unclear. This study evaluates the efficacy and safety of RCHOP, R2-CHOP (RCHOP plus lenalidomide), and RCHOP plus Bruton's Tyrosine Kinase inhibitors (BTKi) in DE-DLBCL treatment.

Methods

Data from 213 DE-DLBCL patients treated from January 2019 and February 2024. Among them, 112 received R-CHOP, 65 received R2-CHOP, and 36 received R-CHOP plus BTKi. We evaluated clinical characteristics, overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) for each groups.

Results

Baseline characteristics were comparable across groups. ORRs were 95.5 % for R-CHOP, 96.9 % for R2-CHOP, and 97.2 % for R-CHOP plus BTKi, with CR rates of 76.5 %, 80 %, and 75 %, respectively. BTKi significantly improved PFS (p=0.033) but not affect OS (p=0.165). Lenalidomide showed no benefit in PFS (p=0.153) or OS (p=0.351). With median follow-up times of 20.6 months for R-CHOP, 23.5 months for R2-CHOP, and 17.6 months for R-CHOP plus BTKi, the 1-year PFS rates were 73.6 %, 82.2 %, and 93.3 %, and the 1-year OS rates were 96.2 %, 93.2 %, and 100 %, respectively. Grade 3–4 adverse events included leukopenia, neutropenia, and anemia, and thrombocytopenia, with no significant differences among groups.

Conclusion

The addition of BTK inhibitor enhances progression-free survival in DE-DLBCL, especially in advanced-stage patients, without introducing new severe adverse reactions. In contract, adding lenalidomide does not offer additional efficacy or survival benefits.

背景：双表达弥漫大B细胞淋巴瘤（DE-DLBCL）预后较差，最佳治疗策略仍不明确。本研究评估了RCHOP、R2-CHOP（RCHOP加来那度胺）和RCHOP加布鲁顿酪氨酸激酶抑制剂（BTKi）治疗DE-DLBCL的疗效和安全性：数据来自2019年1月至2024年2月接受治疗的213例DE-DLBCL患者。其中，112 人接受了 R-CHOP，65 人接受了 R2-CHOP，36 人接受了 R-CHOP 加 BTKi。我们评估了各组的临床特征、总反应率（ORR）、完全反应率（CR）、无进展生存期（PFS）、总生存期（OS）和不良事件（AEs）：各组的基线特征相当。R-CHOP的ORR为95.5%，R2-CHOP为96.9%，R-CHOP加BTKi为97.2%，CR率分别为76.5%、80%和75%。BTKi能明显改善PFS（p=0.033），但不影响OS（p=0.165）。来那度胺在PFS（p=0.153）或OS（p=0.351）方面均无获益。R-CHOP的中位随访时间为20.6个月，R2-CHOP为23.5个月，R-CHOP加BTKi为17.6个月，1年PFS率分别为73.6%、82.2%和93.3%，1年OS率分别为96.2%、93.2%和100%。3-4级不良反应包括白细胞减少、中性粒细胞减少、贫血和血小板减少，各组间无显著差异：结论：添加BTK抑制剂可提高DE-DLBCL患者的无进展生存期，尤其是晚期患者，且不会带来新的严重不良反应。结论：添加BTK抑制剂可提高DE-DLBCL患者的无进展生存期，尤其是晚期患者，但不会带来新的严重不良反应。

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引用次数: 0

Causal role of genetically predicted 731 immune cell phenotypes in chronic lymphatic leukemia: A bidirectional Mendelian randomization study 基因预测的 731 种免疫细胞表型在慢性淋巴白血病中的因果作用：一项双向孟德尔随机化研究。

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-11-09 DOI: 10.1016/j.leukres.2024.107621

Suying Qian, Jiali Gong, Xiu Shen, Mengjie Chen, Yiquan Cheng, Jingwen Zhu, Mengmeng Huang, Zhilong Shi, Gangfeng Xiao, Keyue Hu, Kesang Li

Introduction

The direct causal relationship between these anomalies and chronic lymphatic leukemia (CLL) remains ambiguous. This study sought to investigate the potential causal link between immune cells and CLL.

Materials and methods

The summary data for genome-wide association studies utilized in this research were sourced from various publicly accessible databases, including the GWAS and FinnGen databases. By amalgamating these extensive genetic resources, we applied an array of cutting-edge Mendelian randomization (MR) analytical techniques. Specifically, we employed the inverse variance weighting (IVW) method, the weighted median method, the MR-Egger method, the Cochran Q test, Leave-One-Out sensitivity analysis, and the weighted model method to rigorously evaluate the potential causal link between multiple immune cell phenotypes and CLL.

Results

IVW analyses consistently demonstrated significant causal associations between five groups of immune cells and CLL. These associations were observed in both forward MR analyses from immune cells to CLL, and reverse MR analyses from CLL to immune cells. The five groups of immune cells under investigation included CD14+ CD16- monocyte Absolute Count, CD4+CD8+ T cell Absolute Count, BAFF-R on IgD- CD27- B cell, HLA DR+ T cell Absolute Count, and CD4+ T cell Absolute Count. Further sensitivity analyses not only confirmed the consistency in the direction of the association but also ruled out potential heterogeneity and horizontal pleiotropy effects. This enhanced the robustness and reliability of the study findings.

Conclusion

This investigation discerned definitive causal links between five immune cell phenotypes and CLL, underscoring the pivotal role of immune cells in the pathogenesis of this disease.

导言：免疫细胞异常与慢性淋巴性白血病（CLL）之间的直接因果关系仍不明确。本研究试图调查免疫细胞与 CLL 之间的潜在因果关系：本研究使用的全基因组关联研究的摘要数据来自各种可公开访问的数据库，包括 GWAS 和 FinnGen 数据库。通过整合这些广泛的基因资源，我们应用了一系列尖端的孟德尔随机化（MR）分析技术。具体来说，我们采用了反方差加权（IVW）法、加权中位数法、MR-Egger 法、Cochran Q 检验、留空敏感性分析和加权模型法，以严格评估多种免疫细胞表型与 CLL 之间的潜在因果联系：IVW分析一致表明，五组免疫细胞与CLL之间存在显著的因果关系。从免疫细胞到 CLL 的正向 MR 分析和从 CLL 到免疫细胞的反向 MR 分析都观察到了这些关联。研究的五组免疫细胞包括 CD14+ CD16- 单核细胞绝对计数、CD4+CD8+ T 细胞绝对计数、IgD- CD27- B 细胞上的 BAFF-R、HLA DR+ T 细胞绝对计数和 CD4+ T 细胞绝对计数。进一步的敏感性分析不仅证实了关联方向的一致性，还排除了潜在的异质性和水平褶积效应。这增强了研究结果的稳健性和可靠性：这项研究发现了五种免疫细胞表型与 CLL 之间的明确因果关系，强调了免疫细胞在该疾病发病机制中的关键作用。

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