Pub Date : 2025-10-14DOI: 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.
{"title":"Real-world treatment patterns and clinical outcomes of patients with treatment-naïve and relapsed/refractory diffuse large B-cell lymphoma in the United States","authors":"Jennifer K. Lue , Priyanka J. Bobbili , Mahek Garg , Christopher W. Yee , Katherine E. Ryland , Sonia Gupta , Daisy Liu , Monika Raut , Mei Sheng Duh","doi":"10.1016/j.leukres.2025.108117","DOIUrl":"10.1016/j.leukres.2025.108117","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Patients and Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>This study highlights the need for improved treatment options and increased access to novel therapies, emphasizing gaps in community oncology settings.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"159 ","pages":"Article 108117"},"PeriodicalIF":2.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517199","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}
Pub Date : 2025-10-12DOI: 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.
{"title":"The role of interim bone marrow assessments in acute myeloid leukemia – A systematic review and meta-analysis","authors":"Yuanli Lei , Zhiting Tang , Jessica A. Reese , Omer Jamy , Mohamad Khawandanah , Manu Pandey , Muhammad Faisal , Adam Asch , Zimu Gong","doi":"10.1016/j.leukres.2025.108121","DOIUrl":"10.1016/j.leukres.2025.108121","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Result</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"159 ","pages":"Article 108121"},"PeriodicalIF":2.2,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318432","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}
Pub Date : 2025-10-10DOI: 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.
{"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}
Pub Date : 2025-10-08DOI: 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。
{"title":"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","authors":"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","doi":"10.1016/j.leukres.2025.108120","DOIUrl":"10.1016/j.leukres.2025.108120","url":null,"abstract":"<div><div>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 <em>Staphylococcus epidermidis</em>, 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.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"158 ","pages":"Article 108120"},"PeriodicalIF":2.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301700","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}
Pub Date : 2025-10-06DOI: 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
{"title":"Applicability of current prognostication models for MDS patients with DDX41 mutation","authors":"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","doi":"10.1016/j.leukres.2025.108118","DOIUrl":"10.1016/j.leukres.2025.108118","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"158 ","pages":"Article 108118"},"PeriodicalIF":2.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268631","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}
Pub Date : 2025-10-03DOI: 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。
{"title":"Low serum complement C3 levels are associated with adverse clinical outcomes in myelodysplastic syndromes","authors":"Duobing Zou , Huanhuan Ying , Liang Yong , Jie Cao , Yanqing Liu , Guifang Ouyang , Qitian Mu","doi":"10.1016/j.leukres.2025.108116","DOIUrl":"10.1016/j.leukres.2025.108116","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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).</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"158 ","pages":"Article 108116"},"PeriodicalIF":2.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268630","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}
Pub Date : 2025-09-30DOI: 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.
{"title":"Multicenter retrospective analysis of the short-term efficacy and safety of the VAH regimen in the treatment of acute myeloid leukemia","authors":"Ruihua Mi , Lin Chen , Lin Wang , Haiping Yang , Hongmian Zhao , Sun Wu , Yixuan Ma , Jia Liu , Xudong Wei","doi":"10.1016/j.leukres.2025.108114","DOIUrl":"10.1016/j.leukres.2025.108114","url":null,"abstract":"<div><h3>Objective</h3><div>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).</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"159 ","pages":"Article 108114"},"PeriodicalIF":2.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145390688","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}
Pub Date : 2025-09-27DOI: 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.
{"title":"Evaluating complete response/remission rate as a surrogate endpoint in relapsed/refractory chronic lymphocytic leukemia","authors":"Lin Wang , Murat Kurt , Tim Disher , Fei Fei Liu , Samantha Craigie , Serena K. Perna , Elise Aronitz , Toby A. Eyre , Loic Ysebaert , Matthew S. Davids","doi":"10.1016/j.leukres.2025.108113","DOIUrl":"10.1016/j.leukres.2025.108113","url":null,"abstract":"<div><div>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 %<img>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.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"158 ","pages":"Article 108113"},"PeriodicalIF":2.2,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258507","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}
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.
{"title":"Genes with altered expression by 5-Aza treatment in myeloid leukemia cells through methylation in intron 1","authors":"Machiko Fujioka , Hiroyuki Mishima , Hidehiro Itonaga , Yo Hamaguchi , Uladzislau Korzun , Koji Ando , Akira Kinoshita , Yasushi Miyazaki , Koh-ichiro Yoshiura","doi":"10.1016/j.leukres.2025.108112","DOIUrl":"10.1016/j.leukres.2025.108112","url":null,"abstract":"<div><div>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 (<em>HDC</em> and <em>MICALL2</em>) with increased expression in leukemia cells after 5-Aza treatment were associated with better overall survival, while six genes (<em>BTG2</em>, <em>CD52</em>, <em>PECAM1</em>, <em>PIK3IP1</em>, <em>PTGS2</em>, and <em>TREML2</em>) 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.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"158 ","pages":"Article 108112"},"PeriodicalIF":2.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156766","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}
Pub Date : 2025-09-19DOI: 10.1016/j.leukres.2025.108110
Neville Lee Jr, Katie Erdos, Aqib Abdul Rahman, Richard T. Silver, Joseph M. Scandura, Ghaith Abu-Zeinah
{"title":"Low-dose ropeginterferon alfa-2b and peginterferon alfa-2a have comparable efficacy and tolerability in polycythemia vera","authors":"Neville Lee Jr, Katie Erdos, Aqib Abdul Rahman, Richard T. Silver, Joseph M. Scandura, Ghaith Abu-Zeinah","doi":"10.1016/j.leukres.2025.108110","DOIUrl":"10.1016/j.leukres.2025.108110","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"158 ","pages":"Article 108110"},"PeriodicalIF":2.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154641","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}