Leukemia research最新文献_第6页

Health system costs and autologous stem cell transplant receipt for participants with multiple myeloma in the Australian 45 and Up Study 澳大利亚45岁及以上研究中多发性骨髓瘤参与者的医疗系统费用和自体干细胞移植收据。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-11-01 Epub Date: 2025-09-16 DOI: 10.1016/j.leukres.2025.108100

Sarsha Yap , Anna Kelly , David Goldsbury , Marianne F. Weber , Xue Qin Yu , Qingwei Luo , Karen Canfell , Eleonora Feletto

Background

In Australia, the number of people living with multiple myeloma (MM) is projected to increase. We examined the health system costs and autologous stem cell transplant (ASCT) receipt among participants with MM diagnosed between 2006 and 2019 from the Australian 45 and Up Study cohort (267,357 participants).

Materials and methods

We identified 520 participants diagnosed with MM using cancer registry records. Direct excess health system costs were calculated by subtracting the mean values observed for 2533 matched participants without cancer from those observed for participants with MM. Costs were calculated from 2 years pre-diagnosis up to 5 years post-diagnosis, for different phases of care and at end of life. Participant characteristics associated with health system costs were analysed using gamma regression. Characteristics associated with ASCT receipt were analysed using competing risks regression.

Results

Mean excess health system cost per person was $8846 in the year pre-diagnosis and peaked at $66,249 in the year post-diagnosis. From 2- to 5-years post-diagnosis, mean excess costs per person ranged between $36,453 and $43,059 and remained substantially higher than pre-diagnosis levels. Within the 5-years post-diagnosis, 125 (24.0 %) received ASCT. Older age at diagnosis was strongly associated with lower costs (each one-year increase, relative rate (RR)= 0.97, 95 % CI:0.96–0.98 for initial phase of care costs) and a lower rate of ASCT (each one-year increase, sub-hazard ratio (SHR)= 0.85, 95 % CI:0.83–0.87).

Conclusions

Health system costs for individuals with MM were significantly higher post-diagnosis than pre-diagnosis and remained elevated for at least 5-years. This work provides insights for future healthcare requirements for MM.

背景：在澳大利亚，患有多发性骨髓瘤（MM）的人数预计会增加。我们检查了2006年至2019年澳大利亚45岁及以上研究队列（267,357名参与者）中诊断为MM的参与者的卫生系统成本和自体干细胞移植（ASCT）接收情况。材料和方法：我们使用癌症登记记录确定了520名被诊断为MM的参与者。直接超额卫生系统成本是通过减去2533名没有癌症的匹配参与者观察到的平均值来计算的，从诊断前2年到诊断后5年，计算不同护理阶段和生命结束时的成本。使用伽玛回归分析了与卫生系统成本相关的参与者特征。使用竞争风险回归分析与ASCT接收相关的特征。结果：诊断前一年人均超额卫生系统费用为8846美元，诊断后一年最高为66249美元。从诊断后2年到5年，平均每人额外费用在36,453美元到43,059美元之间，仍然大大高于诊断前的水平。诊断后5年内，125例（24.0 %）接受ASCT。诊断年龄越大与较低的费用（每一年增加，相对率(RR)= 0.97,95 % CI:0.96-0.98初始阶段护理费用）和较低的ASCT率（每一年增加，亚危险比(SHR)= 0.85,95 % CI:0.83-0.87）密切相关。结论：MM患者的医疗系统成本在诊断后明显高于诊断前，并且在至少5年内保持高水平。这项工作为MM的未来医疗保健需求提供了见解。

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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 : 2025-11-01 Epub 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

Genes with altered expression by 5-Aza treatment in myeloid leukemia cells through methylation in intron 1 5-Aza处理通过内含子1甲基化改变髓系白血病细胞表达的基因

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-11-01 Epub Date: 2025-09-23 DOI: 10.1016/j.leukres.2025.108112

Machiko Fujioka , Hiroyuki Mishima , Hidehiro Itonaga , Yo Hamaguchi , Uladzislau Korzun , Koji Ando , Akira Kinoshita , Yasushi Miyazaki , Koh-ichiro Yoshiura

5-Azacitidine (5-Aza) is a hypomethylating agent with demonstrated therapeutic efficacy for myeloid leukemia. The aim of this study was to identify the genes that mediate the cell killing effect of 5-Aza against leukemia cells through their expression changes and DNA demethylation. RNA sequencing revealed 54 genes with increased transcription levels in both SKM-1 and KG-1a myeloid leukemia cell lines treated with 5-Aza. Long read sequencing revealed 79 genes in which intron 1 exhibited significant DNA demethylation after 5-Aza treatment. Forty-three genes showed both increased gene expression and DNA demethylation in intron 1 in cells treated with 5-Aza. Enrichment signaling pathway analysis demonstrated that genes were associated with “amino acid metabolism,” “neutrophil degranulation,” and “DNA damage response”. We evaluated the prognostic impacts of the 43 genes in acute myeloid leukemia patients using TCGA database. The results revealed that two genes (HDC and MICALL2) with increased expression in leukemia cells after 5-Aza treatment were associated with better overall survival, while six genes (BTG2, CD52, PECAM1, PIK3IP1, PTGS2, and TREML2) correlated with worse overall survival. This study revealed that the epigenetic regulation by DNA demethylation in intron 1 has an important role of 5-Aza treatment in myeloid leukemia cells, and suggests novel targets for the development of combination therapy with 5-Aza.

5-氮杂胞苷（5-Aza）是一种低甲基化药物，具有治疗髓性白血病的疗效。本研究的目的是通过5-Aza表达变化和DNA去甲基化来确定介导5-Aza对白血病细胞杀伤作用的基因。RNA测序显示，在5-Aza处理的SKM-1和KG-1a髓系白血病细胞株中，54个基因的转录水平升高。长读测序显示，在5-Aza处理后，79个基因的内含子1出现了显著的DNA去甲基化。在5-Aza处理的细胞中，43个基因在内含子1上的基因表达和DNA去甲基化都增加。富集信号通路分析表明，基因与“氨基酸代谢”、“中性粒细胞脱粒”和“DNA损伤反应”相关。我们使用TCGA数据库评估43个基因对急性髓系白血病患者预后的影响。结果显示，5-Aza治疗后，2个基因（HDC和MICALL2）在白血病细胞中表达增加与更好的总生存相关，而6个基因（BTG2、CD52、PECAM1、PIK3IP1、PTGS2和TREML2）与更差的总生存相关。本研究揭示了内含子1 DNA去甲基化的表观遗传调控在5-Aza治疗髓系白血病细胞中具有重要作用，并为开发5-Aza联合治疗提供了新的靶点。

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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 : 2025-11-01 Epub 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

Efficacy and safety of blinatumomab for CD19 + acute leukemias in patients historically excluded from clinical trials due to comorbidities blinatumomab治疗因合并症而被排除在临床试验之外的CD19 + 急性白血病患者的疗效和安全性

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-01 Epub Date: 2025-09-04 DOI: 10.1016/j.leukres.2025.108098

J. Preston Claiborne , Daniel Li , Hua-Ling Tsai , Gabriel Ghiaur , B. Douglas Smith , Mark J. Levis , Amy E. DeZern , Alex J. Ambinder , Tania Jain , Gabrielle T. Prince , Lukasz P. Gondek , Theodoros Karantanos , W. Brian Dalton , Ivana Gojo , Jonathan A. Webster

Background

Blinatumomab has proven efficacy in the frontline, consolidation, and relapsed/refractory settings in B cell acute lymphoblastic leukemia. Its efficacy and safety among patients commonly excluded from clinical trials are unknown.

Patients and Methods

This single center, retrospective cohort study included patients treated for acute leukemia with blinatumomab with the following pre-existing conditions: liver dysfunction, renal impairment, central nervous system (CNS) conditions, autoimmune disease, solid organ transplantation, or uncontrolled infection. Rates of blinatumomab completion, efficacy outcomes, cytokine release syndrome (CRS), neurotoxicity (ICANS), and adverse events specific to the impaired organ leading to inclusion were assessed.

Results

Thirty-four patients were included, and 88 % completed at least one cycle of blinatumomab. One patient stopped prematurely due to toxicity and three due to lack of response in the relapsed/refractory setting. Response rates and survival were similar by treatment setting to those treated in clinical trials. The 60-day cumulative incidence of grade ≥ 2 CRS and ICANS were 23.5 % and 20.8 %, respectively. No excess liver injury, ICANS, autoimmune flares, organ rejection, or infections were observed in cohorts defined by impairment of each system.

Conclusion

Blinatumomab was successfully administered to the vast majority of patients with a baseline condition that would have led to clinical trial exclusion. Adverse events generally occurred at rates similar to prior clinical trials. These data provide the basis to consider removing certain exclusion criteria from future studies involving blinatumomab, allowing more patients to benefit from its efficacy.

背景：blinatumumab已被证明在B细胞急性淋巴细胞白血病的一线、巩固和复发/难治性治疗中有效。它在通常被排除在临床试验之外的患者中的疗效和安全性尚不清楚。患者和方法：这项单中心、回顾性队列研究纳入了接受blinatumomab治疗的急性白血病患者，这些患者先前存在以下疾病：肝功能障碍、肾功能损害、中枢神经系统（CNS）疾病、自身免疫性疾病、实体器官移植或无法控制的感染。评估blinatumomab完成率、疗效结果、细胞因子释放综合征（CRS）、神经毒性（ICANS）和导致纳入受损器官的特异性不良事件。结果：纳入34例患者，88 %完成了至少一个blinatumumab周期。1名患者因毒性过早停药，3名患者因复发/难治性缺乏反应而停药。治疗组的有效率和生存率与临床试验中的治疗组相似。≥ 2级CRS和ICANS的60天累积发生率分别为23.5% %和20.8% %。在每个系统受损的队列中，没有观察到过度的肝损伤、ICANS、自身免疫耀斑、器官排斥或感染。结论：blinatumumab成功地应用于绝大多数基线条件可能导致临床试验被排除的患者。不良事件的发生率与之前的临床试验相似。这些数据为考虑从未来涉及blinatumomab的研究中删除某些排除标准提供了基础，使更多的患者受益于其疗效。

{"title":"Efficacy and safety of blinatumomab for CD19 + acute leukemias in patients historically excluded from clinical trials due to comorbidities","authors":"J. Preston Claiborne , Daniel Li , Hua-Ling Tsai , Gabriel Ghiaur , B. Douglas Smith , Mark J. Levis , Amy E. DeZern , Alex J. Ambinder , Tania Jain , Gabrielle T. Prince , Lukasz P. Gondek , Theodoros Karantanos , W. Brian Dalton , Ivana Gojo , Jonathan A. Webster","doi":"10.1016/j.leukres.2025.108098","DOIUrl":"10.1016/j.leukres.2025.108098","url":null,"abstract":"<div><h3>Background</h3><div>Blinatumomab has proven efficacy in the frontline, consolidation, and relapsed/refractory settings in B cell acute lymphoblastic leukemia. Its efficacy and safety among patients commonly excluded from clinical trials are unknown.</div></div><div><h3>Patients and Methods</h3><div>This single center, retrospective cohort study included patients treated for acute leukemia with blinatumomab with the following pre-existing conditions: liver dysfunction, renal impairment, central nervous system (CNS) conditions, autoimmune disease, solid organ transplantation, or uncontrolled infection. Rates of blinatumomab completion, efficacy outcomes, cytokine release syndrome (CRS), neurotoxicity (ICANS), and adverse events specific to the impaired organ leading to inclusion were assessed.</div></div><div><h3>Results</h3><div>Thirty-four patients were included, and 88 % completed at least one cycle of blinatumomab. One patient stopped prematurely due to toxicity and three due to lack of response in the relapsed/refractory setting. Response rates and survival were similar by treatment setting to those treated in clinical trials. The 60-day cumulative incidence of grade ≥ 2 CRS and ICANS were 23.5 % and 20.8 %, respectively. No excess liver injury, ICANS, autoimmune flares, organ rejection, or infections were observed in cohorts defined by impairment of each system.</div></div><div><h3>Conclusion</h3><div>Blinatumomab was successfully administered to the vast majority of patients with a baseline condition that would have led to clinical trial exclusion. Adverse events generally occurred at rates similar to prior clinical trials. These data provide the basis to consider removing certain exclusion criteria from future studies involving blinatumomab, allowing more patients to benefit from its efficacy.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"157 ","pages":"Article 108098"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080943","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

Treatment patterns and survival outcomes for very elderly patients with acute myeloid leukemia: A National Cancer Database study 高龄急性髓性白血病患者的治疗模式和生存结果：一项国家癌症数据库研究

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-01 Epub Date: 2025-08-18 DOI: 10.1016/j.leukres.2025.108086

Tina Y. Zhang , Alex Y. Ge , Mara M. Epstein , Shyam A. Patel

Patients 80 years and older with acute myeloid leukemia (AML) are often not candidates for curative-intent treatments, and there is no standard algorithm for leukemia-directed management in this population. There is limited information on their treatment outcomes, especially since the availability of novel targeted options. We used the National Cancer Database to estimate overall survival for 31,195 patients diagnosed with AML at age 80 years and older between 2004 and 2021 and compared survival over time and across available treatment and sociodemographic variables. Median overall survival (mOS) was 1.71 months (95 % confidence interval [CI]: 1.68–1.74 months) and significantly longer in patients 80–84 years old compared to those 85 years and older (2.17 months, 95 % CI: 2.07–2.23 vs. 1.31 months, 95 % CI: 1.28–1.38; p < 0.01). mOS for those treated with multi-agent chemotherapy (MAC) was longer than those treated with single-agent regimens (5.95 months, 95 % CI: 5.52–6.34 vs. 3.38 months, 95 % CI: 3.22–3.52; p < 0.01). The proportion of patients receiving chemotherapy increased from 35 % in 2004-2008 to 56 % in 2019–2021 (p < 0.01) and use of multi-agent treatments increased from 26 % in 2004-2008 to 53 % in 2019–2021 (p < 0.01). In summary, significant gains in mOS were noted in 2019–2021, along with increased use of MAC, possibly due to the introduction of novel therapies such as venetoclax. Future work will focus on understanding complex treatment decisions for very elderly patients and the effect of contemporary MAC options such as hypomethylating agents and venetoclax on treatment patterns and survival.

80岁及以上的急性髓性白血病（AML）患者通常不适合治疗目的治疗，并且在这一人群中没有针对白血病的标准治疗算法。关于其治疗结果的信息有限，特别是因为有新的靶向选择。我们使用国家癌症数据库来估计2004年至2021年期间31,195名80岁及以上诊断为AML的患者的总生存率，并比较了随时间推移、可用治疗和社会人口变量的生存率。中位总生存期（mOS）为1.71个月（95 %可信区间[CI]: 1.68-1.74个月），80-84岁患者的中位总生存期（mOS）明显高于85岁及以上患者（2.17个月，95 % CI: 2.07-2.23 vs. 1.31个月，95 % CI: 1.28-1.38; p <； 0.01）。多药化疗组（MAC）的mOS比单药化疗组（5.95个月，95 % CI: 5.52-6.34 vs. 3.38个月，95 % CI: 3.22-3.52; p <； 0.01）更长。接受化疗的患者比例从2004-2008年的35% %增加到2019-2021年的56% (p <； 0.01)，多药治疗的使用从2004-2008年的26% %增加到2019-2021年的53% （p <； 0.01）。综上所述，2019-2021年，mo的显著增加，同时MAC的使用也在增加，这可能是由于引入了venetoclax等新疗法。未来的工作将集中于了解老年患者的复杂治疗决策，以及当代MAC选择（如低甲基化药物和venetoclax）对治疗模式和生存的影响。

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引用次数: 0

DDGP-based chemoradiotherapy versus radiotherapy alone in newly diagnosed early-stage extranodal NK/T-cell lymphoma: A single-center retrospective analysis 基于ddgp的放化疗与单独放疗治疗新诊断的早期结外NK/ t细胞淋巴瘤：单中心回顾性分析

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-01 Epub Date: 2025-07-19 DOI: 10.1016/j.leukres.2025.107921

Jinmiao Sun , Di Wang , Ziteng Xie, Yu Chang, Mingzhi Zhang, Lei Zhang

To determine the optimal treatment for early-stage extranodal NK/T-cell lymphoma (ENKTL), the efficacy differences between chemoradiotherapy (CRT) and radiotherapy (RT) alone, and between sequential DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) followed by RT (DDGP+RT) versus RT followed by DDGP (RT+DDGP) were investigated. This study compared RT alone versus CRT using DDGP regimen in 189 early-stage ENKTL patients. CRT showed higher objective response rates (95.0% vs 88.0 %, P > 0.05) and significantly improved 10-year PFS (81.3 % vs 54.0 %, P < 0.001) and OS (91.4 % vs 87.3 %, P = 0.029) versus RT alone. DDGP followed by RT (DDGP+RT) achieved superior ORR (98.7 % vs 90.2 %, P = 0.043) and better 10-year PFS in patients with elevated β2-microglobulin (94.4 % vs 57.1 %, P = 0.025) compared to RT followed by DDGP. Multivariate analysis identified RT alone (HR=4.207, P＜0.001), and elevated LDH (HR=4.906, P = 0.012) as poor prognostic factors. CRT sequencing did not significantly affect survival outcomes. These findings demonstrate CRT's superiority over RT alone and suggest β2-MG may guide optimal treatment sequencing in early-stage ENKTL.

为了确定早期结外NK/ t细胞淋巴瘤（ENKTL）的最佳治疗方法，研究了放化疗（CRT）和单纯放疗（RT）以及顺序DDGP（地塞米松、顺铂、吉西他滨和pegaspargase）加放疗（DDGP+RT）与RT加DDGP （RT+DDGP）的疗效差异。本研究比较了189例早期ENKTL患者的单独放疗与使用DDGP方案的CRT。CRT显示更高的客观反应率(95.0% vs 88.0 % P 祝辞 0.05)和显著提高10年期PFS (81.3 vs 54.0  % % P & lt; 0.001)和操作系统(91.4 vs 87.3  % % P = 0.029)和RT孤单。与RT + DDGP相比，DDGP+RT在β2-微球蛋白升高患者中获得了更高的ORR（98.7 % vs 90.2 %,P = 0.043）和更好的10年PFS（94.4 % vs 57.1% %,P = 0.025）。多因素分析发现，单纯放疗（HR=4.207， P<0.001）和LDH升高（HR=4.906, P = 0.012）是不良预后因素。CRT测序对生存结果没有显著影响。这些发现表明CRT优于单独RT，并提示β2-MG可能指导早期ENKTL的最佳治疗顺序。

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引用次数: 0

Menin inhibitors in KMT2A-rearranged leukemia: Mechanistic insights, clinical trial progress, and potential of combination therapies Menin抑制剂治疗kmt2a重排白血病：机制、临床试验进展和联合治疗的潜力

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-01 Epub Date: 2025-07-28 DOI: 10.1016/j.leukres.2025.107924

Xinyu Yang , Rui Huang

Leukemia driven by rearrangement of the Lysine Methyltransferase 2 A (KMT2A) gene, formerly known as mixed-lineage leukemia (MLL), is associated with poor prognosis due to the formation of oncogenic fusion proteins. Menin, a scaffold protein encoded by the MEN1 gene, plays a critical role in the pathogenesis of KMT2A-rearranged (KMT2A-r) leukemia. Targeting menin has emerged as a promising therapeutic strategy, leading to the development of several menin inhibitors, some of which have entered clinical trials. Notably, Revumenib has been approved for clinical use. However, resistance to menin inhibition is an increasing concern, necessitating alternative approaches. Combining menin inhibitors with other therapeutic strategies appears to enhance efficacy and mitigate resistance. This review summarizes recent advancements in menin inhibitor research for KMT2A-r leukemia, including mechanistic insights and clinical trial progress, while also exploring the potential of combination therapies. A deeper understanding of the mechanisms underlying menin inhibition and resistance is crucial for developing more effective treatments to improve patient outcomes.

由赖氨酸甲基转移酶2 A （KMT2A）基因重排驱动的白血病，以前称为混合谱系白血病（MLL），由于形成致癌融合蛋白而与预后不良相关。Menin是一种由MEN1基因编码的支架蛋白，在kmt2a -重排（KMT2A-r）白血病的发病机制中起关键作用。靶向menin已成为一种有前景的治疗策略，导致几种menin抑制剂的开发，其中一些已进入临床试验。值得注意的是，Revumenib已被批准用于临床应用。然而，对menin抑制的耐药性是一个日益关注的问题，需要替代方法。将menin抑制剂与其他治疗策略联合使用似乎可以提高疗效并减轻耐药性。本文综述了近年来menin抑制剂治疗KMT2A-r白血病的研究进展，包括机制见解和临床试验进展，同时也探讨了联合治疗的潜力。更深入地了解menin抑制和耐药性的机制对于开发更有效的治疗方法以改善患者的预后至关重要。

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引用次数: 0

Effect of sorafenib on prognosis in patients with low-allelic-ratio FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation 索拉非尼对低等位基因比FLT3-ITD急性髓系白血病异体造血干细胞移植患者预后的影响

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-01 Epub Date: 2025-08-26 DOI: 10.1016/j.leukres.2025.108088

Qiannan Yang , Zhengwen Ding , Yujie Liu , Suning Chen , Xiaowen Tang , Ying Wang , Hongjie Shen , Yang Xu , Depei Wu , Jinyan Xiao

Background

The effect of sorafenib in acute myeloid leukemia (AML) patients with low-allelic-ratio FMS-like tyrosine kinase 3 internal tandem duplication(FLT3-ITD^{low AR}) is still unclear. Objective: The purpose of this study was to evaluate whether sorafenib can improve prognosis in FLT3-ITD^{low AR} AML patients. Study Design: In this study, the effect of sorafenib on the prognosis of patients with FLT3-ITD^{low AR} AML was retrospectively explored. A total of 112 patients with FLT3-ITD^{low AR} AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) were enrolled, including 44 patients who received sorafenib treatment and 68 patients who did not receive sorafenib. Results: With a 27-month median follow-up, there was no significant difference in overall survival (OS) or Relapse-free survival (RFS) between the sorafenib and control groups (2-year OS: 54.4 % vs. 52.3 %, p = 0.64; 2-year RFS: 49.2 % vs. 36.6 %, p = 0.25). However, for patients with refractory/relapsed (R/R) disease (sorafenib group: n = 29, control group: n = 20), patients in the sorafenib group had better 2-year OS (2-year OS: 22.7 % vs. 15 %, p = 0.018) and RFS (2-year RFS: 36.4 % vs. 10 %, p = 0.051) than did those in the control group. Additionally, multivariate analysis confirmed that receiving sorafenib therapy was an independent protective factor for OS in R/R FLT3-ITD^{low AR} AML patients. Conclusion: Overall, the use of sorafenib could improve outcomes in R/R AML patients with FLT3-ITD^{low AR} mutations.

背景索拉非尼对低等位基因比fms样酪氨酸激酶3内部串联重复（FLT3-ITDlow AR）的急性髓系白血病（AML）患者的作用尚不清楚。目的：本研究的目的是评估索拉非尼是否可以改善FLT3-ITDlow AR AML患者的预后。研究设计：本研究回顾性探讨索拉非尼对FLT3-ITDlow AR AML患者预后的影响。共纳入112例接受同种异体造血干细胞移植（alloo - hsct）的FLT3-ITDlow AR AML患者，其中44例接受索拉非尼治疗，68例未接受索拉非尼治疗。结果：在27个月的中位随访中，索拉非尼组和对照组的总生存率（OS）或无复发生存率（RFS）无显著差异（2年OS: 54.4 % vs. 52.3 %,p = 0.64；2年RFS: 49.2 % vs. 36.6 %,p = 0.25）。然而,对于耐火材料/复发患者(R / R)疾病(索拉非尼组:n = 29日,对照组:n = 20),在索拉非尼组患者最好2年操作系统(2年操作系统:22.7 %与15 %,p = 0.018)和RFS(2年RFS: 36.4 %与10 %,p = 0.051)比对照组。此外，多变量分析证实，接受索拉非尼治疗是R/R FLT3-ITDlow AR AML患者发生OS的独立保护因素。结论：总体而言，使用索拉非尼可以改善FLT3-ITDlow AR突变的R/R AML患者的预后。

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引用次数: 0

Targeting growth signals in leukemia: A case of mistaken identity 靶向白血病生长信号：一个误认的案例

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-01 Epub Date: 2025-08-12 DOI: 10.1016/j.leukres.2025.107935

Sophie G. Kellaway

引用次数: 0