Leukemia research最新文献_第3页

High JAK2V617F allele burden in low-risk PV: an additional recommendation to start “early” cytoreduction? Results from a multicentric study 低风险PV患者JAK2V617F等位基因负担高：“早期”细胞减少的额外建议？来自多中心研究的结果。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-22 DOI: 10.1016/j.leukres.2025.108123

Luca Tosoni, Sara Di Giusto, Gianluca Morelli, Melissa Bergnach, Chiara Callegari, Rossella Stella, Francesco Zaja, Antonia Schwab, Albert Wölfler, Eleonora Toffoletti, Daniela Damiani, Renato Fanin, Mario Tiribelli

引用次数: 0

Exosomal miR-140–3p produced by bone marrow stromal cells affects acute myeloid leukemia cell growth and apoptosis by targeting SUZ12 骨髓基质细胞产生的外泌体miR-140-3p通过靶向SUZ12影响急性髓系白血病细胞的生长和凋亡

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-16 DOI: 10.1016/j.leukres.2025.108122

Jiajia Li , Feifan Li , Mengmeng Zhang , Yanping Wu , Meng Wang , Pingping Zhang

There is growing evidence that exosomes produced by bone marrow stromal cells (BMSCs) are associated with the progression of several cancers, including acute myeloid leukemia (AML), but intrinsic molecular mechanisms remain elusive. Here, we applied previous microarray analysis (GSE133276 and GSE209871) to identify differentially expressed exosomal miRNAs in BMSCs of AML patients, and candidate miR-140–3p, miR-142–5p and miR-142–3p were selected. This study aimed to investigate whether BMSCs affects AML progression are mediated by the candidates, and to explore regulatory mechanisms. The levels of the candidates were examined in bone marrow and BMSCs from AML patients, and exosomes from BMSCs of normal subjects and AML cells by qRT-PCR. Cell proliferation and apoptosis of AML cells co-cultured with BMSCs were detected through CCK-8, colony formation, flow cytometry, and Caspase-3 activity assays with manipulation of the candidate miRNAs expression. RNA pull-down and luciferase reporter assays to identify the downstream target mRNAs of the miRNAs. We confirmed that miR-140–3p, miR-142–5p and miR-142–3p levels were downregulated in bone marrow and BMSCs of AML patients, and were significantly enriched in exosomes of BMSCs but not AML cells. BMSCs co-cultured with AML cells could transfer these miRNAs into AML cells, and suppressed the proliferative potential and promoted the apoptotic behavior of AML cells. Furthermore, miR-140–3p agomir in BMSCs exacerbated the effects of the co-culture system on the AML cell proliferation and apoptosis, which were attenuated by miR-140–3p antagomir. In contrast, co-culture data showed that miR-142–5p and miR-142–3p had no significant effect on cell proliferation and apoptosis. Moreover, SUZ12 polycomb repressive complex 2 subunit (SUZ12) was directly targeted by miR-140–3p, overexpression or inhibition of SUZ12 in AML cells partially counteracted miR-140–3p agomir or antagomir-mediated cellular effects, respectively. Our study suggested that the BMSCs-derived exosomal miR-140–3p, rather than miR-142–5p and miR-142–3p, has a regulatory effect on the growth and apoptosis of AML cells by targeting SUZ12.

越来越多的证据表明，骨髓基质细胞（BMSCs）产生的外泌体与包括急性髓性白血病（AML）在内的几种癌症的进展有关，但其内在的分子机制尚不清楚。在这里，我们应用先前的微阵列分析（GSE133276和GSE209871）来鉴定AML患者骨髓间质干细胞中差异表达的外泌体mirna，并选择候选miR-140-3p， miR-142-5p和miR-142-3p。本研究旨在探讨骨髓间充质干细胞影响AML进展是否由候选药物介导，并探讨其调控机制。通过qRT-PCR检测候选蛋白在AML患者骨髓和骨髓间充质干细胞中的水平，以及正常受试者骨髓间充质干细胞和AML细胞的外泌体中的水平。通过CCK-8、集落形成、流式细胞术和Caspase-3活性测定以及操纵候选miRNAs的表达，检测AML细胞与BMSCs共培养的细胞增殖和凋亡。RNA下拉和荧光素酶报告基因检测鉴定mirna的下游靶mrna。我们证实，miR-140-3p、miR-142-5p和miR-142-3p水平在AML患者骨髓和骨髓间充质干细胞中下调，在骨髓间充质干细胞外泌体中显著富集，而在AML细胞中不富集。骨髓间充质干细胞与AML细胞共培养可将这些mirna转移到AML细胞中，抑制AML细胞的增殖潜能，促进AML细胞的凋亡行为。此外，BMSCs中的miR-140-3p阿塔戈米尔加重了共培养系统对AML细胞增殖和凋亡的影响，miR-140-3p阿塔戈米尔可以减弱这种影响。相比之下，共培养数据显示miR-142-5p和miR-142-3p对细胞增殖和凋亡无显著影响。此外，miR-140-3p直接靶向了SUZ12多梳抑制复合物2亚基（SUZ12）， AML细胞中SUZ12的过表达或抑制分别部分抵消了miR-140-3p agomir或antagomir介导的细胞效应。我们的研究表明，bmscs来源的外泌体miR-140-3p，而不是miR-142-5p和miR-142-3p，通过靶向SUZ12对AML细胞的生长和凋亡具有调节作用。

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引用次数: 0

Real-world treatment patterns and clinical outcomes of patients with treatment-naïve and relapsed/refractory diffuse large B-cell lymphoma in the United States 美国treatment-naïve和复发/难治性弥漫性大b细胞淋巴瘤患者的现实世界治疗模式和临床结果

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-14 DOI: 10.1016/j.leukres.2025.108117

Jennifer K. Lue , Priyanka J. Bobbili , Mahek Garg , Christopher W. Yee , Katherine E. Ryland , Sonia Gupta , Daisy Liu , Monika Raut , Mei Sheng Duh

Background

With the evolving treatment landscape and growing therapeutic options, it is essential to understand the treatments currently used in real-world clinical practice and the associated outcomes among patients with DLBCL to identify potential unmet treatment needs.

Patients and Methods

This retrospective longitudinal cohort study examined treatment patterns and outcomes for diffuse large B-cell lymphoma (DLBCL) patients using the COTA electronic health records database from 2016 to 2023. The study population included 3569 patients, treated in community oncology settings, who received first-line (1L) therapy.

Results

Nineteen percent of patients relapsed after 1L chemoimmunotherapy (primarily R-CHOP). The most common second-line treatments included rituximab-based regimens and autologous stem cell transplant (ASCT). Antibody-drug conjugates (ADCs) and CAR T-cell therapy were administered in third-line or later. Median progression-free survival (PFS) and overall survival (OS) decreased with each line. Relapsed/refractory real-world DLBCL patients experienced poor outcomes (24-month OS of 41.7 %). Patients receiving ASCT or CAR T-cell therapy had better OS than those who did not receive cellular therapies, with 24-month OS of 78 %, 54 %, and 31 %, respectively.

Conclusion

This study highlights the need for improved treatment options and increased access to novel therapies, emphasizing gaps in community oncology settings.

随着治疗领域的发展和治疗选择的增加，了解目前在现实世界的临床实践中使用的治疗方法以及DLBCL患者的相关结果对于识别潜在的未满足的治疗需求至关重要。患者和方法本回顾性纵向队列研究使用COTA电子健康记录数据库，检查2016年至2023年弥漫性大b细胞淋巴瘤（DLBCL）患者的治疗模式和结果。研究人群包括3569名在社区肿瘤学机构接受一线（1L）治疗的患者。结果1L化疗免疫治疗（以R-CHOP为主）后复发的患者占19%。最常见的二线治疗包括基于利妥昔单抗的方案和自体干细胞移植（ASCT）。抗体-药物偶联物（adc）和CAR - t细胞治疗在三线或后期进行。中位无进展生存期（PFS）和总生存期（OS）随着每条线而下降。现实世界中复发/难治性DLBCL患者的预后较差（24个月OS为41.7 %）。接受ASCT或CAR - t细胞治疗的患者比未接受细胞治疗的患者有更好的OS， 24个月的OS分别为78 %，54 %和31 %。结论：该研究强调了改善治疗方案和增加新疗法可及性的必要性，强调了社区肿瘤环境中的差距。

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引用次数: 0

The role of interim bone marrow assessments in acute myeloid leukemia – A systematic review and meta-analysis 中期骨髓评估在急性髓性白血病中的作用——一项系统回顾和荟萃分析。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-12 DOI: 10.1016/j.leukres.2025.108121

Yuanli Lei , Zhiting Tang , Jessica A. Reese , Omer Jamy , Mohamad Khawandanah , Manu Pandey , Muhammad Faisal , Adam Asch , Zimu Gong

Background

The current standard of care for acute myeloid leukemia (AML) patients undergoing intensive induction chemotherapy includes an interim bone marrow biopsy around day 14 (D14BM), and reinduction for patients with more than 5 % residual blasts on D14BM (Positive D14BM). However, this approach has become increasingly controversial. This systematic review and meta-analysis assess the sensitivity, specificity, and predictive value of D14BM in patients treated with one cycle of induction chemotherapy and evaluate the efficacy of reinduction versus observation in patients with Positive D14BM.

Methods

A systematic literature search was conducted using PubMed, Embase, Web of Science, and Cochrane databases. A bivariate model was used for pooled sensitivity and specificity. The positive predictive value was estimated based on pooled mean sensitivity, specificity, and historical refractory leukemia prevalence. Risk ratios (RR) for complete remission (CR) were meta-analyzed to compare reinduction versus observation in Positive D14BM patients.

Result

Among 1044 identified articles, 12 met inclusion criteria. Ten studies (1683 patients) evaluated the predictive value of D14BM, with a sensitivity of 49.7 % (proportion of refractory cases correctly identified by Positive D14BM) and specificity of 86.2 %. The estimated positive predictive value was 38.9 %, assuming a 15 % prevalence of true refractory leukemia. Eleven studies (832 patients) evaluated efficacy of reinduction, with a pooled RR of 1.00 (61 % vs. 60 %, 95 % CI: 0.76–1.31) for CR.

Conclusion

Positive D14BM has limited predictive power for refractory leukemia. Reinduction based on Positive D14BM does not improve CR rates compared to observation alone only and may expose patients to undue toxicity.

背景：目前接受强化诱导化疗的急性髓性白血病（AML）患者的护理标准包括在第14天左右（D14BM）进行中期骨髓活检，并对D14BM上残余细胞超过 % （D14BM阳性）的患者进行再诱导。然而，这种方法已经变得越来越有争议。本系统综述和荟萃分析评估了D14BM在接受一个周期诱导化疗的患者中的敏感性、特异性和预测价值，并评估了D14BM阳性患者再诱导与观察的疗效。方法：采用PubMed、Embase、Web of Science、Cochrane等数据库进行系统文献检索。双变量模型用于合并敏感性和特异性。阳性预测值是根据汇总的平均敏感性、特异性和难治性白血病的历史患病率来估计的。对完全缓解（CR）的风险比（RR）进行荟萃分析，比较D14BM阳性患者的再诱导和观察。结果：1044篇文献中，有12篇符合纳入标准。10项研究（1683例患者）评估了D14BM的预测价值，其敏感性为49.7 %（阳性D14BM正确识别的难治性病例比例），特异性为86.2 %。估计阳性预测值为38.9 %，假设真正难治性白血病的患病率为15 %。11项研究（832例患者）评估了再诱导对cr的疗效，合并RR为1.00（61 %对60 %，95 % CI: 0.76-1.31）。结论：D14BM阳性对难治性白血病的预测能力有限。与单独观察相比，基于阳性D14BM的再诱导不能提高CR率，并可能使患者暴露于过度的毒性。

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引用次数: 0

IGF2BP3 promotes acute myeloid leukemia cell progression by regulating Semaphorin 4D stability in an m6A-dependent manner IGF2BP3通过m6a依赖的方式调节Semaphorin 4D的稳定性，从而促进急性髓系白血病细胞的进展。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-10 DOI: 10.1016/j.leukres.2025.108119

Juan Li , Shulan Shi , Kefu Zhu , Linyang Zhe , Tianle Lu , Quanzhen Deng , Qingfang Li , Qiuling Hou , Tilong Huang , Qiangming Sun , Ming Yu , Hongchao Jiang

Background

Our previous findings indicate Semaphorin 4D (Sema4D) as a potential pediatric leukemia biomarker, promoting leukemogenesis via PI3K/AKT and ERK pathways, but its upstream regulatory mechanisms remain unclear. This study was conducted to explore the potential regulatory relationship between Insulin growth factor 2 mRNA binding protein 3 (IGF2BP3) and Sema4D in acute myeloid leukemia (AML).

Methods

The expression levels of Sema4D and IGF2BP3 were analyzed in PBMCs from 41 newly diagnosed patients with pediatric acute myeloid leukemia (AML) and 35 healthy pediatric donors who presented no history of leukemia using western blotting and qRT-PCR. IGF2BP3 overexpression and knockdown models were established in Kasumi-1 and HL-60 cells via lentiviral infection. Cell proliferation, apoptosis, and cell cycle distribution were assessed using CCK-8 and flow cytometry. The stability of Sema4D mRNA and m6A methylation levels were evaluated via mRNA stability assay and qPCR.

Results

This study discovered that Sema4D and IGF2BP3 were overexpressed in the peripheral blood mononuclear cells (PBMCs) of AML patients, and their expression levels were positively correlated. IGF2BP3 overexpression enhanced cell proliferation and cell cycle progression, and inhibited apoptosis in AML cells, while knockdown had the opposite effect. Mechanistic exploration revealed that IGF2BP3 enhances the stability of Sema4D mRNA through m6A-dependent mechanisms.

Conclusion

In this study, we demonstrate that the IGF2BP3/Sema4D axis is a crucial regulator in AML development, driving cell proliferation and survival through post-transcriptional regulation of Sema4D by IGF2BP3 in an m6A-dependent manner. Our findings highlight the potential of targeting this axis as a therapeutic strategy for AML treatment.

背景：我们之前的研究结果表明，信号蛋白4D （Sema4D）是一种潜在的儿科白血病生物标志物，通过PI3K/AKT和ERK途径促进白血病的发生，但其上游调控机制尚不清楚。本研究旨在探讨胰岛素生长因子2 mRNA结合蛋白3 （IGF2BP3）与Sema4D在急性髓性白血病（AML）中的潜在调控关系。方法：应用western blotting和qRT-PCR分析41例小儿急性髓性白血病（AML）新诊断患者和35例无白血病病史的健康儿童供者外周血中Sema4D和IGF2BP3的表达水平。通过慢病毒感染在Kasumi-1和HL-60细胞中建立IGF2BP3过表达和低表达模型。采用CCK-8和流式细胞术评估细胞增殖、凋亡和细胞周期分布。通过mRNA稳定性测定和qPCR评估Sema4D mRNA和m6A甲基化水平的稳定性。结果：本研究发现，Sema4D和IGF2BP3在AML患者外周血单个核细胞（PBMCs）中过表达，且表达水平呈正相关。IGF2BP3过表达增强AML细胞增殖和细胞周期进程，抑制细胞凋亡，而敲低则相反。机制探索表明，IGF2BP3通过m6a依赖性机制增强Sema4D mRNA的稳定性。结论：在本研究中，我们证明了IGF2BP3/Sema4D轴在AML发展中是一个重要的调节因子，通过IGF2BP3以m6a依赖的方式转录后调节Sema4D，驱动细胞增殖和存活。我们的发现强调了靶向这一轴作为AML治疗策略的潜力。

{"title":"IGF2BP3 promotes acute myeloid leukemia cell progression by regulating Semaphorin 4D stability in an m6A-dependent manner","authors":"Juan Li , Shulan Shi , Kefu Zhu , Linyang Zhe , Tianle Lu , Quanzhen Deng , Qingfang Li , Qiuling Hou , Tilong Huang , Qiangming Sun , Ming Yu , Hongchao Jiang","doi":"10.1016/j.leukres.2025.108119","DOIUrl":"10.1016/j.leukres.2025.108119","url":null,"abstract":"<div><h3>Background</h3><div>Our previous findings indicate Semaphorin 4D (Sema4D) as a potential pediatric leukemia biomarker, promoting leukemogenesis via PI3K/AKT and ERK pathways, but its upstream regulatory mechanisms remain unclear. This study was conducted to explore the potential regulatory relationship between Insulin growth factor 2 mRNA binding protein 3 (IGF2BP3) and Sema4D in acute myeloid leukemia (AML).</div></div><div><h3>Methods</h3><div>The expression levels of Sema4D and IGF2BP3 were analyzed in PBMCs from 41 newly diagnosed patients with pediatric acute myeloid leukemia (AML) and 35 healthy pediatric donors who presented no history of leukemia using western blotting and qRT-PCR. IGF2BP3 overexpression and knockdown models were established in Kasumi-1 and HL-60 cells via lentiviral infection. Cell proliferation, apoptosis, and cell cycle distribution were assessed using CCK-8 and flow cytometry. The stability of Sema4D mRNA and m6A methylation levels were evaluated via mRNA stability assay and qPCR.</div></div><div><h3>Results</h3><div>This study discovered that Sema4D and IGF2BP3 were overexpressed in the peripheral blood mononuclear cells (PBMCs) of AML patients, and their expression levels were positively correlated. IGF2BP3 overexpression enhanced cell proliferation and cell cycle progression, and inhibited apoptosis in AML cells, while knockdown had the opposite effect. Mechanistic exploration revealed that IGF2BP3 enhances the stability of Sema4D mRNA through m6A-dependent mechanisms.</div></div><div><h3>Conclusion</h3><div>In this study, we demonstrate that the IGF2BP3/Sema4D axis is a crucial regulator in AML development, driving cell proliferation and survival through post-transcriptional regulation of Sema4D by IGF2BP3 in an m6A-dependent manner. Our findings highlight the potential of targeting this axis as a therapeutic strategy for AML treatment.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"159 ","pages":"Article 108119"},"PeriodicalIF":2.2,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445437","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}

引用次数: 0

Infectious complications in pediatric acute lymphoblastic leukemia treatment: A comparison of ALL-IC BFM 2009 vs. modified St. Jude total XV in a single-center retrospective cohort study 儿科急性淋巴细胞白血病治疗中的感染并发症：一项单中心回顾性队列研究中ALL-IC BFM 2009与改良St. Jude total XV的比较

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-08 DOI: 10.1016/j.leukres.2025.108120

Dilara Unal , Fatma Gumruk , Selin Aytac , Baris Kuskonmaz , Muhammed Dogukan Aksu , Fatma Visal Okur , Tekin Aksu , Mehmet Ceyhan , Ates Kara , Ali Bulent Cengiz , Yasemin Ozsurekci , Sule Unal

Infectious complications remain the major cause of treatment-related morbidity and mortality in pediatric patients with acute lymphoblastic leukemia (ALL). This study retrospectively compared the patterns of infection in children treated with either the modified St. Jude Total XV protocol (n = 181) or the ALL-IC BFM 2009 protocol (n = 61) at a single center. Although the overall number of infection episodes was similar between the two groups, their distributions across treatment phases differed markedly. The ALL-IC BFM 2009 protocol was associated with a significantly greater incidence of infections during the induction phase, particularly in high-risk patients, who often presented with skin and gastrointestinal tract infections. In contrast, modified St. Jude Total XV protocol presented a greater infection risk during the re-induction phase. Gram-positive bacteria, especially Staphylococcus epidermidis, were the most frequently isolated pathogens in both cohorts, although the BFM group exhibited a higher proportion of gram-negative infections. The rates of documented viral infections in BFM cohort and modified St. Jude Total XV cohort were 21.4 % vs 9.2 %, respectively. Invasive fungal infection rate was found as 6.7 % in the modified St. Jude group and 4.0 % in the BFM group is in line with the literature. Multivariate analysis confirmed that severe neutropenia and the presence of a central venous catheter were strong independent predictors of infection frequency. These findings underscore protocol-specific differences in infectious risk profiles and emphasize the importance of tailored supportive care strategies in the management of pediatric ALL.

感染性并发症仍然是急性淋巴细胞白血病（ALL）患儿治疗相关发病率和死亡率的主要原因。本研究回顾性比较了在单个中心接受改良St. Jude Total XV方案（n = 181）或ALL-IC BFM 2009方案（n = 61）治疗的儿童感染模式。尽管两组之间感染事件的总次数相似，但它们在治疗阶段的分布明显不同。ALL-IC BFM 2009方案与诱导期感染发生率显著增加相关，特别是在经常出现皮肤和胃肠道感染的高危患者中。相比之下，改良的St. Jude Total XV方案在再诱导阶段的感染风险更大。革兰氏阳性细菌，尤其是表皮葡萄球菌，是两个队列中最常见的分离病原体，尽管BFM组表现出更高比例的革兰氏阴性感染。BFM队列和改良St. Jude Total XV队列中记录的病毒感染率分别为21.4% %和9.2% %。改良St. Jude组侵袭性真菌感染率为6.7 %，BFM组为4.0 %，与文献一致。多因素分析证实，严重中性粒细胞减少和中心静脉导管的存在是感染频率的强大独立预测因素。这些发现强调了不同方案在感染风险概况方面的差异，并强调了在儿科ALL治疗中定制支持性护理策略的重要性。

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引用次数: 0

Applicability of current prognostication models for MDS patients with DDX41 mutation 当前DDX41突变MDS患者预后模型的适用性

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-06 DOI: 10.1016/j.leukres.2025.108118

Nadia Toumeh, Yazan Jabban, Rong He, David Viswanatha, Dragan Jevremovic, Patricia T. Greipp, James M. Foran, Talha Badar, Cecilia Y. Arana Yi, Yael Kusne, Antoine N. Saliba, Mehrdad Hefazi Thorghabeh, Aasiya Matin, William J. Hogan, Mithun V. Shah, Abhishek A. Mangaonkar, Mrinal M. Patnaik, Hassan B. Alkhateeb, Aref Al-Kali

引用次数: 0

Low serum complement C3 levels are associated with adverse clinical outcomes in myelodysplastic syndromes 低血清补体C3水平与骨髓增生异常综合征的不良临床结果相关

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-03 DOI: 10.1016/j.leukres.2025.108116

Duobing Zou , Huanhuan Ying , Liang Yong , Jie Cao , Yanqing Liu , Guifang Ouyang , Qitian Mu

Background

Complement C3, a critical component of the complement system, has been implicated in cancer risk across various malignancies. However, its role in myelodysplastic syndromes (MDS) remains inadequately explored. This study investigates the impact of serum complement C3 levels on survival outcomes in patients with MDS.

Methods

Clinical data, including demographic characteristics (sex and age), hematological indices (white blood cell count and platelet count), bone marrow blast percentage, immunoglobulin levels (IgG, IgM, and IgA), and complement components (C3, C4, and Factor B), were retrospectively analyzed in 145 patients with MDS. Serum C3 levels were compared quantitatively between healthy controls and patients with MDS. Univariate and multivariate Cox proportional hazards regression analyses were employed to identify prognostic factors associated with clinical outcomes in MDS.

Results

A significant reduction in peripheral blood complement C3 levels was observed in patients with MDS compared to healthy controls (P < 0.0001). Patients with lower serum C3 levels exhibited notably poorer clinical outcomes, including reduced overall survival (OS; P = 0.019) and leukemia-free survival (LFS; P = 0.043). Multivariate Cox regression analysis, incorporating the Revised International Prognostic Scoring System (IPSS-R) but not the Molecular IPSS (IPSS-M), identified serum C3 levels below 79 mg/dL as an independent prognostic factor for both OS (P = 0.041) and LFS (P = 0.005).

Conclusion

Decreased serum complement C3 levels emerge as an independent prognostic biomarker in MDS, correlating with unfavorable clinical outcomes regardless of IPSS-R stratification. This novel parameter offers additional prognostic value and may enhance existing risk assessment tools in the clinical management of MDS.

补体C3是补体系统的一个重要组成部分，与各种恶性肿瘤的癌症风险有关。然而，其在骨髓增生异常综合征（MDS）中的作用仍未得到充分探讨。本研究探讨血清补体C3水平对MDS患者生存结局的影响。方法回顾性分析145例MDS患者的临床资料，包括人口统计学特征（性别、年龄）、血液学指标（白细胞计数、血小板计数）、骨髓原细胞百分比、免疫球蛋白水平（IgG、IgM、IgA）和补体成分（C3、C4、因子B）。定量比较健康对照组和MDS患者血清C3水平。采用单因素和多因素Cox比例风险回归分析来确定与MDS临床结果相关的预后因素。结果与健康对照组相比，MDS患者外周血补体C3水平显著降低（P <； 0.0001）。血清C3水平较低的患者表现出明显较差的临床结果，包括总生存期（OS; P = 0.019）和无白血病生存期（LFS; P = 0.043）降低。纳入修订国际预后评分系统（IPSS- r）而非分子IPSS （IPSS- m）的多变量Cox回归分析发现，血清C3水平低于79 mg/dL是OS （P = 0.041）和LFS （P = 0.005）的独立预后因素。结论血清补体C3水平降低是MDS的独立预后生物标志物，与IPSS-R分层无关，与不利的临床结果相关。这一新参数提供了额外的预后价值，并可能增强MDS临床管理中现有的风险评估工具。

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引用次数: 0

Multicenter retrospective analysis of the short-term efficacy and safety of the VAH regimen in the treatment of acute myeloid leukemia 多中心回顾性分析VAH方案治疗急性髓性白血病的短期疗效和安全性。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-09-30 DOI: 10.1016/j.leukres.2025.108114

Ruihua Mi , Lin Chen , Lin Wang , Haiping Yang , Hongmian Zhao , Sun Wu , Yixuan Ma , Jia Liu , Xudong Wei

Objective

To retrospectively investigate the short-term efficacy and safety of the triple-drug combination regimen of venetoclax + azacitidine + homoharringtonine (VAH regimen) in patients with acute myeloid leukemia (AML).

Methods

Retrospective analysis was conducted on a total of 45 patients with newly diagnosed or refractory/relapsed AML, who were admitted to the Affiliated Cancer Hospital of Zhengzhou University, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, the Huaihe Hospital of Henan University, and The First Affiliated Hospital of Xinxiang Medical University from July 2022 to October 2024 and treated with the VAH regimen. The overall response rate and safety of this regimen were analyzed, and the relevant literature was reviewed.

Results

In the 23 newly treated patients, the overall response rate (ORR) (CR+CRi) was 65.2 % on day 15 of the VAH regimen and 82.6 % on day 29 after the end of cycle 1. The median duration of grade 3–4 neutropenia was 12.6 days. In the 22 refractory/relapsed patients, the ORR (CR+CRi) was 68.2 % on day 15 of the VAH regimen and 86.4 % on day 29 after the end of cycle 1, and the median duration of neutropenia was 14.4 days. The most common adverse reactions were myelosuppression and infection, both of which were within controllable limits. There was no death due to adverse reactions during treatment.

Conclusion

The VAH regimen yields a high remission rate in newly diagnosed and refractory/relapsed AML patients. This retrospective study provides a novel treatment strategy for AML patients.

目的：回顾性探讨维尼托克拉克斯+ 阿扎胞苷+ 高杉碱三联用药方案（VAH方案）治疗急性髓性白血病（AML）的近期疗效和安全性。方法：回顾性分析2022年7月至2024年10月在郑州大学附属肿瘤医院、河南科技大学第一附属医院及临床医学院、河南大学淮河医院、新乡医科大学第一附属医院接受VAH方案治疗的45例新诊断或难治/复发AML患者。分析该方案的总有效率和安全性，并对相关文献进行复习。结果：在23例新治疗的患者中，VAH方案第15天总缓解率（CR+CRi）为65.2% %，第1周期结束后第29天为82.6 %。3-4级中性粒细胞减少的中位持续时间为12.6天。在22例难治/复发患者中，VAH方案第15天的ORR （CR+CRi）为68.2% %，第1周期结束后第29天的ORR （CR+CRi）为86.4 %，中性粒细胞减少的中位持续时间为14.4天。最常见的不良反应是骨髓抑制和感染，均在可控范围内。治疗期间无不良反应死亡病例。结论：VAH方案对新诊断和难治性/复发AML患者有很高的缓解率。本回顾性研究为AML患者提供了一种新的治疗策略。

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引用次数: 0

Evaluating complete response/remission rate as a surrogate endpoint in relapsed/refractory chronic lymphocytic leukemia 评估完全缓解/缓解率作为复发/难治性慢性淋巴细胞白血病的替代终点

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-09-27 DOI: 10.1016/j.leukres.2025.108113

Lin Wang , Murat Kurt , Tim Disher , Fei Fei Liu , Samantha Craigie , Serena K. Perna , Elise Aronitz , Toby A. Eyre , Loic Ysebaert , Matthew S. Davids

Achieving complete response/remission (CR) by International Workshop on Chronic Lymphocytic Leukemia 2018 criteria indicates complete remission of leukemia in all disease compartments. We evaluated CR rate as a surrogate endpoint for progression-free survival (PFS) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) using data from randomized controlled trials (RCT). A systematic literature review was conducted to identify RCTs with ≥ 2 treatment arms, parallel group design, and reporting CR rate and PFS in patients with R/R CLL/SLL. Association between treatment effects on CR rate and corresponding PFS changes contrasting treatment and control arms was estimated using a weighted linear model, Daniels and Hughes model, and Riley bivariate random-effects meta-analysis. Association between absolute CR rate and PFS within individual treatment arms was estimated using nonparametric (Cox) and parametric (exponential, Weibull, Gompertz) proportional hazards models. Twenty RCTs were identified including 5765 patients with R/R CLL/SLL investigating various treatments (Bruton tyrosine kinase inhibitors, a B-cell lymphoma 2 inhibitor, phosphatidylinositol 3-kinase inhibitors, chimeric antigen receptor T-cell therapy, anti-CD20 monoclonal antibody, chemotherapy). Across RCTs, higher odds of CR resulted in statistically significant lower hazards of disease progression/death, where each 10 % increase in CR rate was associated with a 26 % (95 % confidence interval, 22 %30 %) reduction in risk of progression/death. Cross-validation analyses demonstrated that treatment effects on CR rate reasonably predicted PFS benefits. Results were broadly consistent across different models. This study supports CR rate as an essential treatment goal and a valid surrogate endpoint in R/R CLL/SLL.

达到国际慢性淋巴细胞白血病研讨会2018标准的完全缓解/缓解（CR）表明所有疾病区室的白血病完全缓解。我们使用随机对照试验（RCT）的数据评估了CR率作为复发/难治性（R/R）慢性淋巴细胞白血病(CLL)/小淋巴细胞淋巴瘤（SLL）患者无进展生存（PFS）的替代终点。通过系统的文献综述，确定≥ 2个治疗组、平行组设计、报告R/R CLL/SLL患者的CR率和PFS的rct。采用加权线性模型、Daniels和Hughes模型和Riley双变量随机效应荟萃分析，估计治疗效果对CR率和相应PFS变化的相关性。使用非参数（Cox）和参数（指数、Weibull、Gompertz）比例风险模型估计各个治疗组中绝对CR率和PFS之间的关联。共纳入20项随机对照试验，包括5765例R/R CLL/SLL患者，研究了各种治疗方法（布鲁顿酪氨酸激酶抑制剂、b细胞淋巴瘤2抑制剂、磷脂酰肌醇3激酶抑制剂、嵌合抗原受体t细胞治疗、抗cd20单克隆抗体、化疗）。在所有随机对照试验中，较高的CR几率导致疾病进展/死亡风险的统计学显著降低，其中CR率每增加10 %，进展/死亡风险降低26 %（95 %可信区间，22 %30 %）。交叉验证分析表明，治疗对CR率的影响合理地预测了PFS的益处。不同模型的结果大致一致。本研究支持CR率作为R/R CLL/SLL的基本治疗目标和有效替代终点。

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