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Malnutrition defined by Controlling Nutritional Status score was independently associated with prognosis of diffuse large B-cell lymphoma primarily on elderly patients.
IF 2 4区 医学 Q3 HEMATOLOGY Pub Date : 2025-12-01 Epub Date: 2024-12-19 DOI: 10.1080/16078454.2024.2434276
Fei Wang, Luo Lu, Haoyu Zang, Yanhua Yue, Yang Cao, Min Chen, Yue Liu, Weiying Gu, Bai He

Objectives: Controlling Nutritional Status (CONUT) Score is an effective tool for the assessment of malnutrition and proved to be associated with survival of Diffuse large B-cell lymphoma (DLBCL) patients. We investigated the impact of CONUT score on specific subgroups of DLBCL patients, including age and International prognostic Index (IPI) risk groups.

Methods: Data of 287 newly diagnosed DLBCL in the Third Affiliated Hospital of Soochow University were retrospectively collected. Baseline CONUT score, clinical data and survival information were recorded.

Results: With the standard cut-off value of 4 points, 88 (30.7%) patients were clarified as malnourished. During a median follow-up of 34 months, malnourished patients exhibited significant reduction in both progression-free survival (PFS) and overall survival (OS). The 3-year PFS rates for malnourished and well-nourished patients were 51.4% and 70.9% (p = 0.001), while the 3-year OS rates were 62.4% and 84.0% (p < 0.001). Malnutrition was demonstrated an independent predictor of OS in DLBCL patients (HR 2.220, 95% CI 1.307-3.772, p = 0.003). It could effectively identify patients with inferior OS in both low/intermediate-low risk and intermediate-high/high risk IPI groups. In the group of elderly patients aged over 60 years, malnutrition was independently associated with OS (HR 2.182, 95% CI 1.178-4.040, p = 0.024), but not PFS (HR 1.709, 95% CI 1.016-2.875, p = 0.070) after adjustment using the Benjamini-Hochberg procedure. Conversely, for younger patients, malnutrition did not demonstrate an independent impact on either PFS or OS.

Conclusion: Malnutrition evaluated by CONUT score was an independent predictor for the outcome of DLBCL patients, which is exclusively caused by its effect on elderly patients.

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引用次数: 0
Identification of t(X;1)(q28;q21) generating a novel GATAD2B::MTCP1 gene fusion in CMML and its persistence during progression to AML.
IF 2 4区 医学 Q3 HEMATOLOGY Pub Date : 2025-12-01 Epub Date: 2024-12-18 DOI: 10.1080/16078454.2024.2439110
Yi-Zi Liu, Feng-Hong Zhang, Chun-Xiao Hou, Zhi-Yu Zhang, Yi-Yan Zhu, Qian Wang, Yu Chen, Su-Ning Chen

Objective: Hematological malignancies often involve chromosomal translocations and fusion genes that drive disease progression. While MTCP1 is well-known in T-cell prolymphocytic leukemia (T-PLL), its role in myeloid neoplasms is less understood. This report presents the first identification of the t(X;1)(q28;q21) translocation leading to the GATAD2B::MTCP1 fusion in acute myeloid leukemia (AML) transformed from chronic myelomonocytic leukemia (CMML).

Methods: The karyotypes were described according to the International System for Human Cytogenetic Nomenclature 2009. We performed targeted next-generation sequencing (NGS) on a panel of 172 genes commonly mutated in hematological malignancies (Supplemental Table 1), using an Illumina platform. RNA sequencing was conducted on total RNA extracted from bone marrow, also using the Illumina platform. The GATAD2B::MTCP1 fusion gene was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing, with specific primers for the fusion transcript (GATAD2B-F: CCTCTTTTTTTCGACGCC; MTCP1-R: ACTGAGCACAACACTTACGC).

Results: The GATAD2B::MTCP1 fusion results from a breakpoint on 1q21 within GATAD2B exon 1 and Xq28 within MTCP1 exon 2. The patient with the GATAD2B::MTCP1 fusion exhibited disease progression from CMML to AML. Despite achieving initial remission with venetoclax-based therapy and allo-HSCT, the patient relapsed and died.

Conclusions: We propose that the GATAD2B::MTCP1 fusion upregulates MTCP1 expression rather than generating a fusion protein, thereby contributing to transformation and relapse in AML. Further investigations are needed to elucidate the precise role of this fusion event in myeloid malignancies.

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引用次数: 0
Clinical characteristics and prognostic analysis of CDKN2A/2B gene in pediatric acute lymphoblastic leukemia: a retrospective case-control study. 小儿急性淋巴细胞白血病 CDKN2A/2B 基因的临床特征和预后分析:一项回顾性病例对照研究。
IF 2 4区 医学 Q3 HEMATOLOGY Pub Date : 2025-12-01 Epub Date: 2024-12-15 DOI: 10.1080/16078454.2024.2439606
Shi-Mei Huang, Hui-Qin Chen, Li-Ting Liu, Ya-Ting Zhang, Jian Wang, Dun-Hua Zhou, Jian-Pei Fang, Lu-Hong Xu

In this retrospective case-control study involving 424 pediatric patients diagnosed with Pediatric Acute Lymphoblastic Leukemia (ALL), the investigation focused on analyzing the clinical characteristics and prognosis associated with the Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) gene. Treatment and evaluation followed the South China Children's Leukemia Group-ALL-2016 protocol (SCCLG-ALL-2016). Among the cohort, 92 patients (21.7%) exhibited CDKN2A/2B gene deletions, with 11.1% homozygous and 10.6% heterozygous deletions. Notably, ALL patients that do have CDKN2A/2B gene deletions tended to present at an older age (P = 0.001), demonstrate hepatosplenomegaly on palpation (P < 0.001), and exhibit a higher incidence of Central nervous system leukemia (CNSL) (P = 0.037) and T-ALL (P = 0.007). A significant correlation was observed between ALL that does have CDKN2A/2B gene deletions and ETV6::RUNX1-positive (8.7% vs. 19.3%, P = 0.017) and IKZF1 gene deletions (20.7% vs. 8.4%, P = 0.001). Survival analysis of 392 patients revealed no significant differences in 5-year relapse, Overall survival (OS), or Event-free survival (EFS) between ALL that does/ does not have CDKN2A/2B gene deletions. Subgroup analysis highlighted poorer prognosis among hepatosplenomegaly patients in the CDKN2A/2B gene deletion group, with a 5-year EFS of 81.8%, 95%CI (0.695-0.963), P = 0.05. Hepatosplenomegaly emerged as the most significant prognostic factor for EFS [HR = 2.306, 95%CI (1.192-4.461), P = 0.013]. Cox regression analyses identified covariates influencing prognosis, ALL with the CDKN2A/2B gene showing no significant impact on outcomes. In conclusion, while ALL that does have CDKN2A/2B gene deletions is associated with certain clinical characteristics and genetic aberrations, they did not significantly impact OS or EFS. Furthermore, subgroup analysis revealed a potential prognostic role of ALL that does have CDKN2A/2B deletions presenting with hepatosplenomegaly on palpation, emphasizing the importance of comprehensive risk stratification in treatment decision-making for this subgroup.

在这项涉及424名确诊为小儿急性淋巴细胞白血病(ALL)的儿童患者的回顾性病例对照研究中,调查的重点是分析与细胞周期蛋白依赖性激酶抑制剂2A/2B(CDKN2A/2B)基因相关的临床特征和预后。治疗和评估遵循华南儿童白血病组-ALL-2016方案(SCCLG-ALL-2016)。组群中有92名患者(21.7%)出现CDKN2A/2B基因缺失,其中11.1%为同源缺失,10.6%为杂合缺失。值得注意的是,CDKN2A/2B基因缺失的ALL患者往往发病年龄较大(P = 0.001),触诊时表现为肝脾肿大(P P = 0.037)和T-ALL(P = 0.007)。CDKN2A/2B基因缺失的ALL与ETV6::RUNX1阳性(8.7% vs. 19.3%,P = 0.017)和IKZF1基因缺失(20.7% vs. 8.4%,P = 0.001)之间存在明显相关性。对392名患者进行的生存分析表明,有/无CDKN2A/2B基因缺失的ALL患者在5年复发率、总生存率(OS)或无事件生存率(EFS)方面无明显差异。亚组分析显示,CDKN2A/2B基因缺失组肝脾肿大患者的预后较差,5年无事件生存率为81.8%,95%CI (0.695-0.963),P = 0.05。肝脾肿大是影响 EFS 的最重要预后因素[HR = 2.306,95%CI (1.192-4.461),P = 0.013]。Cox回归分析确定了影响预后的协变量,带有CDKN2A/2B基因的ALL对预后无显著影响。总之,虽然CDKN2A/2B基因缺失的ALL与某些临床特征和遗传畸变有关,但它们对OS或EFS没有显著影响。此外,亚组分析表明,CDKN2A/2B基因缺失的ALL患者在触诊时出现肝脾肿大可能对预后有影响,这强调了在对这一亚组患者进行治疗决策时进行全面风险分层的重要性。
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引用次数: 0
IGHG4: innovative diagnostic biomarkers for iron overload in β-thalassemia patients. IGHG4:β-地中海贫血患者铁超载的创新诊断生物标志物。
IF 2 4区 医学 Q3 HEMATOLOGY Pub Date : 2025-12-01 Epub Date: 2024-12-15 DOI: 10.1080/16078454.2024.2433154
Yang Liu, Jinfang Huang, Jianming Luo

Objectives: This study aims to investigate the serotransferrin (TF), complement C1s subcomponent (C1S), immunoglobulin heavy constant gamma 4 (IGHG4), hemoglobin subunit alpha (HBA1), and clusterin (CLU) contents in β-thalassemia patients, and explores their physiological role as potential non-invasive bioindicators for disease diagnosis and iron overload.

Methods: A total of 62 children with β-thalassemia were recruited and categorized by genotype, along with 17 healthy pediatric volunteers for analysis. The circulating ferritin content was evaluated, and plasma levels of TF, C1S, IGHG4, HBA1, and CLU were assessed using ELISA. The primary outcome of this study was the correlation between the five protein marker levels and iron overload. Continuous variables were analyzed using the Student's t-test or the Mann-Whitney U test. A binary logistic regression model identified independent predictors of iron overload in patients with β-thalassemia. Receiver operating characteristics (ROC) were employed to evaluate the model's performance.

Results: The IGHG4 protein content was significantly lower in β-thalassemia patients compared to healthy controls. The IGHG4 protein content was reduced in the β+0 and β00 patient populations compared to controls, with no significant difference observed between the β+0 group and healthy controls. A strong inverse relationship was identified between the IGHG4 protein content and SF concentration (r = -0.322, p = 0.004). Finally, plasma IGHG4 levels demonstrated adequate diagnostic capability, as indicated by our ROC curve analysis.

Conclusion: In conclusion, decreased IGHG4 protein levels are significantly associated with the degree of iron overload in β-thalassemia patients and may serve as a possible biomarker for evaluating iron overload.

{"title":"IGHG4: innovative diagnostic biomarkers for iron overload in β-thalassemia patients.","authors":"Yang Liu, Jinfang Huang, Jianming Luo","doi":"10.1080/16078454.2024.2433154","DOIUrl":"https://doi.org/10.1080/16078454.2024.2433154","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to investigate the serotransferrin (TF), complement C1s subcomponent (C1S), immunoglobulin heavy constant gamma 4 (IGHG4), hemoglobin subunit alpha (HBA1), and clusterin (CLU) contents in β-thalassemia patients, and explores their physiological role as potential non-invasive bioindicators for disease diagnosis and iron overload.</p><p><strong>Methods: </strong>A total of 62 children with β-thalassemia were recruited and categorized by genotype, along with 17 healthy pediatric volunteers for analysis. The circulating ferritin content was evaluated, and plasma levels of TF, C1S, IGHG4, HBA1, and CLU were assessed using ELISA. The primary outcome of this study was the correlation between the five protein marker levels and iron overload. Continuous variables were analyzed using the Student's t-test or the Mann-Whitney U test. A binary logistic regression model identified independent predictors of iron overload in patients with β-thalassemia. Receiver operating characteristics (ROC) were employed to evaluate the model's performance.</p><p><strong>Results: </strong>The IGHG4 protein content was significantly lower in β-thalassemia patients compared to healthy controls. The IGHG4 protein content was reduced in the β<sup>+</sup>/β<sup>0</sup> and β<sup>0</sup>/β<sup>0</sup> patient populations compared to controls, with no significant difference observed between the β<sup>+</sup>/β<sup>0</sup> group and healthy controls. A strong inverse relationship was identified between the IGHG4 protein content and SF concentration (<i>r</i> = -0.322, <i>p </i>= 0.004). Finally, plasma IGHG4 levels demonstrated adequate diagnostic capability, as indicated by our ROC curve analysis.</p><p><strong>Conclusion: </strong>In conclusion, decreased IGHG4 protein levels are significantly associated with the degree of iron overload in β-thalassemia patients and may serve as a possible biomarker for evaluating iron overload.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"30 1","pages":"2433154"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828389","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 of Pediatric Acute Lymphoblastic Leukemia in India as per modified BFM 95 protocol with Minimal Residual Disease monitoring. 在印度,按照修改后的 BFM 95 方案治疗小儿急性淋巴细胞白血病,并进行最小残留病监测。
IF 2 4区 医学 Q3 HEMATOLOGY Pub Date : 2025-12-01 Epub Date: 2024-12-15 DOI: 10.1080/16078454.2024.2439733
Dhwanee Thakkar, K Upasana, D S Udayakumar, Neha Rastogi, Ritu Chadha, Sunisha Arora, Bhawna Jha, Anjali Yadav, Shalini Goel, Renu Saxena, Satya Prakash Yadav

Background: Survival outcomes of Pediatric Acute Lymphoblastic Leukemia (ALL) in the developing world have lagged. Here we report improved outcomes of pediatric ALL from India.Methods: We analyzed outcomes of children with ALL treated at our center between 2016 and 2021. They were treated as per the modified BFM 95 protocol with Minimal Residual Disease (MRD) monitoring by flow cytometry (FCM).Results: We diagnosed and managed 68 patients, 57 being Precursor B (Pre B) cell ALL and the rest of T cell ALL. With BFM 95 protocol-based risk stratification, 19/68, 44/68 and 3/68 patients were Standard risk (SR), Medium risk (MR) and High risk (HR), respectively and 2/68 were not stratified due to Induction mortality. With MRD-based risk stratification, 52/68, 11/68 and 2/68 patients fell in the SR, MR and HR category, respectively and 3/68 patients were not classifiable by MRD (2 Induction deaths and 1 refractory disease) and 65/68 patients achieved morphological complete remission (CR) at the end of Induction. Five out of 68 ALL patients underwent allogeneic hematopoietic stem cell transplant (HSCT) in CR1. Ten out of 68 patients had a relapse, 6 of whom are alive and in CR2 till the last follow-up. The mean duration of follow-up was 1150 days (median 1219 days). Treatment-related mortality was 4.4% in our cohort. The Event Free Survival (EFS) of our cohort was 79.4% and Overall Survival (OS) was 88.2% at a median follow-up of 1219 days.Conclusion: Survival outcomes have improved for children with ALL with modifications in BFM 95 protocol and incorporation of MRD assessment.

背景:发展中国家小儿急性淋巴细胞白血病(ALL)的生存率较低。在此,我们报告了印度小儿急性淋巴细胞白血病治疗效果的改善情况:我们分析了2016年至2021年间在本中心接受治疗的ALL患儿的疗效。他们按照改良的BFM 95方案接受治疗,并通过流式细胞术(FCM)监测最小残留病(MRD):我们诊断并治疗了68例患者,其中57例为前体B(Pre B)细胞ALL,其余为T细胞ALL。根据 BFM 95 方案进行风险分层后,19/68、44/68 和 3/68 患者分别属于标准风险 (SR)、中度风险 (MR) 和高度风险 (HR),2/68 患者因诱导死亡而未进行分层。根据MRD进行风险分层后,52/68、11/68和2/68的患者分别属于SR、MR和HR类别,3/68的患者无法根据MRD进行分类(2例诱导死亡和1例难治性疾病),65/68的患者在诱导结束时实现了形态学完全缓解(CR)。68名ALL患者中有5名在CR1时接受了异基因造血干细胞移植(HSCT)。68名患者中有10人复发,其中6人存活并在最后一次随访中达到CR2。平均随访时间为 1150 天(中位数为 1219 天)。治疗相关死亡率为4.4%。中位随访时间为1219天,无事件生存期(EFS)为79.4%,总生存期(OS)为88.2%:结论:随着BFM 95方案的修改和MRD评估的纳入,ALL患儿的生存率有所提高。
{"title":"Treatment of Pediatric Acute Lymphoblastic Leukemia in India as per modified BFM 95 protocol with Minimal Residual Disease monitoring.","authors":"Dhwanee Thakkar, K Upasana, D S Udayakumar, Neha Rastogi, Ritu Chadha, Sunisha Arora, Bhawna Jha, Anjali Yadav, Shalini Goel, Renu Saxena, Satya Prakash Yadav","doi":"10.1080/16078454.2024.2439733","DOIUrl":"https://doi.org/10.1080/16078454.2024.2439733","url":null,"abstract":"<p><p><b>Background:</b> Survival outcomes of Pediatric Acute Lymphoblastic Leukemia (ALL) in the developing world have lagged. Here we report improved outcomes of pediatric ALL from India.<b>Methods:</b> We analyzed outcomes of children with ALL treated at our center between 2016 and 2021. They were treated as per the modified BFM 95 protocol with Minimal Residual Disease (MRD) monitoring by flow cytometry (FCM).<b>Results:</b> We diagnosed and managed 68 patients, 57 being Precursor B (Pre B) cell ALL and the rest of T cell ALL. With BFM 95 protocol-based risk stratification, 19/68, 44/68 and 3/68 patients were Standard risk (SR), Medium risk (MR) and High risk (HR), respectively and 2/68 were not stratified due to Induction mortality. With MRD-based risk stratification, 52/68, 11/68 and 2/68 patients fell in the SR, MR and HR category, respectively and 3/68 patients were not classifiable by MRD (2 Induction deaths and 1 refractory disease) and 65/68 patients achieved morphological complete remission (CR) at the end of Induction. Five out of 68 ALL patients underwent allogeneic hematopoietic stem cell transplant (HSCT) in CR1. Ten out of 68 patients had a relapse, 6 of whom are alive and in CR2 till the last follow-up. The mean duration of follow-up was 1150 days (median 1219 days). Treatment-related mortality was 4.4% in our cohort. The Event Free Survival (EFS) of our cohort was 79.4% and Overall Survival (OS) was 88.2% at a median follow-up of 1219 days.<b>Conclusion:</b> Survival outcomes have improved for children with ALL with modifications in BFM 95 protocol and incorporation of MRD assessment.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"30 1","pages":"2439733"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828391","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
A RUNX1: RUNX1T1 AML with a simultaneous false positive KMT2A rearrangement: FISH interpretation pitfalls. RUNX1:RUNX1T1急性髓细胞性白血病同时伴有KMT2A重排假阳性:FISH解读陷阱。
IF 2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-13 DOI: 10.1080/16078454.2024.2420306
Chi Zhang, Xingping Lang, Lingfeng Liu, Nan Chen, Huafei Chen, Xiaojun Chen, Yongyan Chen, Liqin Jin, Chengyin Liu, Huan Wang, Ailin Fu, Sheng Xiao

Introduction: KMT2A rearrangement (KMT2Ar) is a common genomic alteration in acute leukemia that can be effectively targeted by menin inhibitors. While FISH is the standard laboratory test for KMT2Ar, false positives can occur.

Case report: We present a case of AML in which both RUNX1::RUNX1T1 and KMT2Ar were identified by karyotype analysis and FISH. Although a targeted RNA next generation sequencing (NGS) assay confirmed the presence of the RUNX1::RUNX1T1 fusion, it did not detect a KMT2A fusion transcript. To investigate the discrepancy between the positive KMT2A FISH result and the negative fusion transcript, we performed whole-genome mate-pair DNA NGS to examine the KMT2A locus on chromosome 11q23. This analysis revealed a breakpoint located 5.8 kb downstream of KMT2A, which did not disrupt the gene itself. Given that KMT2A FISH probes cover approximately 1 Mb around KMT2A, this subtle shift led to a split-apart signal pattern mimicking a genuine KMT2A rearrangement, resulting in a false positive FISH interpretation.

Conclusion: This case highlights a false positive KMT2Ar in primary AML, indicating the need for additional molecular testing for confirmation.

简介KMT2A重排(KMT2Ar)是急性白血病中常见的基因组改变,menin抑制剂可以有效地针对这种改变。虽然 FISH 是 KMT2Ar 的标准实验室检测方法,但也可能出现假阳性:我们报告了一例急性髓细胞白血病病例,该病例通过核型分析和 FISH 发现了 RUNX1::RUNX1T1 和 KMT2Ar。虽然靶向 RNA 下一代测序(NGS)检测证实了 RUNX1::RUNX1T1 融合的存在,但并未检测到 KMT2A 融合转录本。为了研究 KMT2A FISH 阳性结果与阴性融合转录本之间的差异,我们进行了全基因组配对 DNA NGS,以检测染色体 11q23 上的 KMT2A 基因座。这项分析发现了位于 KMT2A 下游 5.8 kb 的断点,但该断点并未破坏基因本身。鉴于 KMT2A FISH 探针覆盖了 KMT2A 周围约 1 Mb 的范围,这种微妙的移动导致了模仿真正的 KMT2A 重排的分裂信号模式,从而导致了 FISH 解释的假阳性:本病例突出显示了原发性急性髓细胞性白血病的 KMT2Ar 假阳性,表明需要进行额外的分子检测来确认。
{"title":"A <i>RUNX1: RUNX1T1</i> AML with a simultaneous false positive <i>KMT2A</i> rearrangement: FISH interpretation pitfalls.","authors":"Chi Zhang, Xingping Lang, Lingfeng Liu, Nan Chen, Huafei Chen, Xiaojun Chen, Yongyan Chen, Liqin Jin, Chengyin Liu, Huan Wang, Ailin Fu, Sheng Xiao","doi":"10.1080/16078454.2024.2420306","DOIUrl":"https://doi.org/10.1080/16078454.2024.2420306","url":null,"abstract":"<p><strong>Introduction: </strong><i>KMT2A</i> rearrangement (<i>KMT2Ar</i>) is a common genomic alteration in acute leukemia that can be effectively targeted by menin inhibitors. While FISH is the standard laboratory test for <i>KMT2Ar</i>, false positives can occur.</p><p><strong>Case report: </strong>We present a case of AML in which both <i>RUNX1::RUNX1T1</i> and <i>KMT2Ar</i> were identified by karyotype analysis and FISH. Although a targeted RNA next generation sequencing (NGS) assay confirmed the presence of the <i>RUNX1::RUNX1T1</i> fusion, it did not detect a <i>KMT2A</i> fusion transcript. To investigate the discrepancy between the positive <i>KMT2A</i> FISH result and the negative fusion transcript, we performed whole-genome mate-pair DNA NGS to examine the <i>KMT2A</i> locus on chromosome 11q23. This analysis revealed a breakpoint located 5.8 kb downstream of <i>KMT2A</i>, which did not disrupt the gene itself. Given that <i>KMT2A</i> FISH probes cover approximately 1 Mb around <i>KMT2A</i>, this subtle shift led to a split-apart signal pattern mimicking a genuine <i>KMT2A</i> rearrangement, resulting in a false positive FISH interpretation.</p><p><strong>Conclusion: </strong>This case highlights a false positive <i>KMT2Ar</i> in primary AML, indicating the need for additional molecular testing for confirmation.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2420306"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619257","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
Reduced duration and dosage of venetoclax is efficient in newly diagnosed patients with acute myeloid leukemia. 缩短 venetoclax 的疗程和剂量对新确诊的急性髓性白血病患者有效。
IF 1.9 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2023-12-14 DOI: 10.1080/16078454.2023.2293512
Jingying Cui, Xuexing Chen, Chunfang Li, Qiong Yan, Guolin Yuan

Objectives: The combination of Venetoclax (VEN) and Azacitidine (AZA) increases survival outcomes and yields excellent responses in patients with acute myeloid leukemia (AML). However, dose reduction (or discontinuation) is commonly encountered due to therapy-related toxicity. Thus, this study aimed to investigate the efficiency and safety of a lower dosage of venetoclax for the treatment of AML.

Methods: This observational study analyzed the characteristics and outcomes of newly diagnosed AML patients who received 100 mg VEN combined with AZA for 14 days at our institution.

Results: A total of 36 patients were enrolled, and the median age at diagnosis was 64 years. After a median follow-up of 15 (range 4-29) months, the median overall survival (OS) and progression-free survival (PFS) for the whole cohort were 17 (4-29) months and 12 (1-28) months, respectively. Meanwhile, the overall response rate (ORR) was 69.4%, and the CRc rate was 66.7% in the whole cohort. Subgroup analysis revealed that NPM1 mutations and FAB-M5 subtype were associated with higher response rates, whereas the adverse ELN risk group was predictive of an inferior response. Moreover, ASXL1, NPM1, and IDH1/2 mutations negatively impacted PFS.

Discussion: Our study optimized the administration of venetoclax plus azacytidine for the treatment of AML patients. Response rates were favorable, with median survival in agreement with the findings of earlier reports, offering valuable insights for optimizing VEN-based regimens.

Conclusion: In summary, the VEN combination regimen is effective for the treatment of newly diagnosed AML patients in the real world despite VEN dose reductions .

研究目的联合使用 Venetoclax(VEN)和阿扎胞苷(AZA)可提高急性髓性白血病(AML)患者的存活率,并产生良好的疗效。然而,由于与治疗相关的毒性,减量(或停药)是常有的事。因此,本研究旨在探讨较低剂量的 Venetoclax 治疗急性髓性白血病的有效性和安全性:这项观察性研究分析了本院接受100毫克VEN联合AZA治疗14天的新诊断AML患者的特征和预后:共有36名患者入组,诊断时的中位年龄为64岁。中位随访时间为 15 个月(4-29 个月),中位总生存期(OS)和无进展生存期(PFS)分别为 17 个月(4-29 个月)和 12 个月(1-28 个月)。同时,整个队列的总反应率(ORR)为69.4%,CRc率为66.7%。亚组分析显示,NPM1突变和FAB-M5亚型与较高的应答率相关,而ELN不良风险组则预示着较差的应答率。此外,ASXL1、NPM1和IDH1/2突变对PFS有负面影响:我们的研究优化了venetoclax加氮杂胞苷治疗急性髓细胞白血病患者的用药。反应率良好,中位生存期与早期报告结果一致,为优化基于VEN的治疗方案提供了有价值的见解:总之,在现实世界中,尽管VEN剂量有所减少,但VEN联合方案对治疗新诊断的急性髓细胞性白血病患者是有效的。
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引用次数: 0
A combined immune and exosome-related risk signature as prognostic biomakers in acute myeloid leukemia. 作为急性髓性白血病预后生物标记的免疫和外泌体相关风险组合特征。
IF 1.9 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-01-07 DOI: 10.1080/16078454.2023.2300855
Zenghui Fang, Jiali Fu, Xin Chen

Objectives: Acute myeloid leukemia (AML) is one of the common hematological diseases with low survival rates. Studies have highlighted the dysregulated expression of immune-related and exosome-related genes (ERGs) in cancers. Nevertheless, it remains to be determined whether combining these genes have a prognostic significance in AML.

Methods: Immune-ERG profiles for 151 AML patients from TCGA were analyzed. A risk model was constructed and optimized through the combination of univariate Cox regression and LASSO regression analysis. GEO datasets were utilized as the external validation for the robustness of the risk model. In addition, we performed KEGG and GO enrichment analyses to investigate the role played by these genes in AML. The variations in immune cell infiltrations among risk groups were assessed through four algorithms. Expression of hub gene in specific cell was analyzed by single-cell RNA seq.

Results: A total of 85 immune-ERGs associated with prognosis were identified, enabling the construction of a risk model for AML. The risk model based on five immune-ERGs (CD37, NUCB2, LSP1, MGST1, and PLXNB1) demonstrated a correlation with the clinical outcomes. Additionally, age, FAB classification, cytogenetics risk, and risk score were identified as independent prognostic factors. The five immune-ERGs exhibited correlations with cytokine-cytokine receptor interaction, and antigen processing and presentation. Notably, the risk model demonstrated significant associations with immune responses and the expression of immune checkpoints.

Conclusions: An immune-ERG-based risk model was developed to effectively predict prognostic outcomes for AML patients. There is potential for immune therapy in AML targeting the five hub genes.

研究目的急性髓性白血病(AML)是生存率较低的常见血液病之一。研究强调了癌症中免疫相关基因和外泌体相关基因(ERGs)的表达失调。然而,这些基因的结合是否对急性髓细胞白血病的预后具有重要意义仍有待确定:方法:分析了 TCGA 中 151 例急性髓细胞性白血病患者的免疫-ERG 图谱。通过结合单变量 Cox 回归和 LASSO 回归分析,构建并优化了风险模型。GEO 数据集被用作风险模型稳健性的外部验证。此外,我们还进行了 KEGG 和 GO 富集分析,以研究这些基因在 AML 中的作用。我们通过四种算法评估了不同风险组免疫细胞浸润的差异。通过单细胞RNA序列分析了枢纽基因在特定细胞中的表达:结果:共鉴定出85个与预后相关的免疫ERG,从而构建了急性髓细胞性白血病的风险模型。基于5个免疫ERG(CD37、NUCB2、LSP1、MGST1和PLXNB1)的风险模型显示与临床结果相关。此外,年龄、FAB分类、细胞遗传学风险和风险评分也被确定为独立的预后因素。五种免疫ERG与细胞因子-细胞因子受体相互作用、抗原处理和递呈存在相关性。值得注意的是,风险模型与免疫反应和免疫检查点的表达有显著关联:结论:基于免疫-ERG的风险模型可以有效预测急性髓细胞白血病患者的预后结果。针对五个枢纽基因的急性髓细胞性白血病免疫疗法具有潜力。
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引用次数: 0
Elucidating the immune landscape and potential prognostic model in acute myeloid leukemia with TP53 mutation. 阐明TP53基因突变的急性髓性白血病的免疫格局和潜在预后模型
IF 2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-27 DOI: 10.1080/16078454.2024.2400620
Gelan Zhu, Jiayi Cai, Wanbin Fu, Yue Sun, Ting Wang, Hua Zhong

Objectives: The TP53 mutation, a prevalent tumor suppressor gene alteration, is linked to chemotherapy resistance, increased relapse rates and diminished overall survival (OS) in acute myeloid leukemia (AML) patients.

Methods: In this study, we characterize the TP53 mutation phenotypes across various AML cohorts utilizing The Cancer Genome Atlas (TCGA) data. We devised a TP53-related prognostic signature derived from differentially expressed genes between mutated and wild-type TP53 AML specimens. In-depth analyses were conducted, encompassing genetic variation, immune cell infiltration and prognostic stratification.

Results: A six-gene TP53-related signature was established using least absolute shrinkage and selection operator (LASSO)-Cox regression, demonstrating robust prognostic predictability. This signature exhibited strong performance in both the OHSU validation cohorts, an independent Gene Expression Omnibus (GEO) validation cohort (GSE71014) and proved by results of the in vivo experiment. Finally, we used single cell database (GSE198681) to observe the characteristics of these six genes.

Discussion: Our study may facilitate the development of efficacious therapeutic approaches and provide a novel idea for future research. Conclusion: The TP53-related signature and pattern hold the potential to refine prognostic stratification and underscore emerging targeted therapies.

研究目的TP53突变是一种常见的肿瘤抑制基因改变,与急性髓性白血病(AML)患者的化疗耐药、复发率增加和总生存期(OS)缩短有关:在这项研究中,我们利用《癌症基因组图谱》(The Cancer Genome Atlas,TCGA)数据描述了不同AML队列中TP53突变表型的特征。我们从突变型和野生型TP53急性髓细胞白血病标本的差异表达基因中设计出了TP53相关预后特征。我们对基因变异、免疫细胞浸润和预后分层进行了深入分析:结果:利用最小绝对收缩和选择算子(LASSO)-Cox 回归法建立了六基因 TP53 相关特征,显示出强大的预后预测能力。该特征在 OHSU 验证队列、独立的基因表达总库(GEO)验证队列(GSE71014)中都表现出很强的性能,体内实验结果也证明了这一点。最后,我们利用单细胞数据库(GSE198681)观察了这六个基因的特征:讨论:我们的研究可能有助于开发有效的治疗方法,并为未来的研究提供了新的思路。结论TP53相关特征和模式具有完善预后分层和强调新兴靶向疗法的潜力。
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引用次数: 0
Clinical features and long-term outcomes of pediatric patients with de novo acute myeloid leukemia in China with or without specific gene abnormalities: a cohort study of patients treated with BCH-AML 2005. 有或无特定基因异常的中国新生儿急性髓性白血病患者的临床特征和长期预后:2005 年 BCH-AML 治疗患者的队列研究。
IF 2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-03 DOI: 10.1080/16078454.2024.2406596
Hongbo He, Jun Li, Weijing Li, Xiaoxi Zhao, Tianlin Xue, Shuguang Liu, Ruidong Zhang, Huyong Zheng, Chao Gao

Acute myeloid leukemia (AML), which has distinct genetic abnormalities, has unique clinical and biological features. In this study, the incidence, clinical characteristics, induction treatment response, and outcomes of a large cohort of Chinese AML pediatric patients treated according to the BCH-AML 2005 protocol were analyzed. RUNX1-RUNX1T1 was the most common fusion transcript, followed by the CBFβ-MHY11 and KMT2A rearrangements. FLT3-ITD and KIT mutations are associated with unfavorable clinical features and induction responses, along with KMT2A rearrangements, DEK-NUP214, and CBF-AML. The 5-year event-free survival (EFS) and overall survival (OS) rates of our cohort were 53.9 ± 3.7% and 58.5 ± 3.6%, with the best survival found among patients with CBFβ-MYH11 and the worst survival among those with DEK-NUP214. In addition, we found that patients with FLT3-ITD mutation had adverse outcomes and that KIT mutation had a negative impact on OS in RUNX1-RUNX1T1+ patients. Furthermore, the risk classification and response to treatment after each induction block also influenced the prognosis, and HSCT after first remission could improve OS in high-risk patients. Not achieving complete remission after induction 2 was found to be an independent prognostic factor for OS and EFS. These findings indicate that genetic abnormalities could be considered stratification factors, predict patient outcomes, and imply the application of targeted therapy.

急性髓性白血病(AML)具有明显的基因异常,并具有独特的临床和生物学特征。本研究分析了一大批按照BCH-AML 2005方案治疗的中国急性髓细胞白血病儿科患者的发病率、临床特征、诱导治疗反应和预后。RUNX1-RUNX1T1是最常见的融合转录本,其次是CBFβ-MHY11和KMT2A重排。FLT3-ITD和KIT突变以及KMT2A重排、DEK-NUP214和CBF-AML与不利的临床特征和诱导反应有关。我们队列中的5年无事件生存率(EFS)和总生存率(OS)分别为53.9±3.7%和58.5±3.6%,其中CBFβ-MYH11患者的生存率最好,而DEK-NUP214患者的生存率最差。此外,我们还发现,FLT3-ITD 突变的患者预后不良,KIT 突变对 RUNX1-RUNX1T1+ 患者的 OS 有负面影响。此外,风险分级和每次诱导阻滞后的治疗反应也会影响预后,首次缓解后进行造血干细胞移植可改善高危患者的 OS。诱导2后未达到完全缓解是影响OS和EFS的独立预后因素。这些研究结果表明,基因异常可作为分层因素,预测患者的预后,并意味着靶向治疗的应用。
{"title":"Clinical features and long-term outcomes of pediatric patients with de novo acute myeloid leukemia in China with or without specific gene abnormalities: a cohort study of patients treated with BCH-AML 2005.","authors":"Hongbo He, Jun Li, Weijing Li, Xiaoxi Zhao, Tianlin Xue, Shuguang Liu, Ruidong Zhang, Huyong Zheng, Chao Gao","doi":"10.1080/16078454.2024.2406596","DOIUrl":"10.1080/16078454.2024.2406596","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML), which has distinct genetic abnormalities, has unique clinical and biological features. In this study, the incidence, clinical characteristics, induction treatment response, and outcomes of a large cohort of Chinese AML pediatric patients treated according to the BCH-AML 2005 protocol were analyzed. <i>RUNX1-RUNX1T1</i> was the most common fusion transcript, followed by the <i>CBFβ-MHY11</i> and <i>KMT2A</i> rearrangements. <i>FLT3</i>-ITD and <i>KIT</i> mutations are associated with unfavorable clinical features and induction responses, along with <i>KMT2A</i> rearrangements, <i>DEK-NUP214</i>, and CBF-AML. The 5-year event-free survival (EFS) and overall survival (OS) rates of our cohort were 53.9 ± 3.7% and 58.5 ± 3.6%, with the best survival found among patients with <i>CBFβ-MYH11</i> and the worst survival among those with <i>DEK-NUP214</i>. In addition, we found that patients with <i>FLT3</i>-ITD mutation had adverse outcomes and that <i>KIT</i> mutation had a negative impact on OS in <i>RUNX1-RUNX1T1</i><sup>+</sup> patients. Furthermore, the risk classification and response to treatment after each induction block also influenced the prognosis, and HSCT after first remission could improve OS in high-risk patients. Not achieving complete remission after induction 2 was found to be an independent prognostic factor for OS and EFS. These findings indicate that genetic abnormalities could be considered stratification factors, predict patient outcomes, and imply the application of targeted therapy.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2406596"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365101","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}
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Hematology
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