Blood and Lymphatic Cancer-Targets and Therapy最新文献

{"title":"Natural Killer/T-Cell Lymphoma-Associated Hemophagocytic lymphohistiocytosis-a Rare and Dangerous Disease.","authors":"Guangqiang Meng, Manzhi Wang, Congcong Sun, Gege Feng, Jing Ren, Saran Feng, Yan Wang","doi":"10.2147/BLCTT.S574445","DOIUrl":"10.2147/BLCTT.S574445","url":null,"abstract":"<p><p>Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome characterised by the reactive activation of cytotoxic T-lymphocytes and macrophages along with a substantial amount of cytokine secretion caused by various inductions. Natural killer/T-cell lymphoma (NKTL)-associated HLH (NK/T-LAHLH) is rare in clinical practice with an incidence rate of 7.1-11.9% in NKTL patients. Currently, there is no standard first-line treatment with good efficacy for NK/T-LAHLH. The treatment of NK/T-LAHLH is still mainly based on chemotherapy regimens containing etoposide and dexamethasone. Recently, many new therapeutic drugs and schemes have been trialled for the treatment of NK/T-LAHLH, such as ruxolitinib, immune checkpoint inhibitors, pegaspargase, and the DEP regimen. However, NK/T-LAHLH is associated with overall poor prognosis. Improving overall understanding of NK/T-LAHLH is of great significance to ameliorating patient prognosis. This review systematically discussed the epidemiology, pathogenesis, clinical features, current treatment regimens, and prognosis of NK/T-LAHLH to comprehensively elucidate this disease.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"574445"},"PeriodicalIF":4.9,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Flumatinib in Patients with Chronic Phase Chronic Myeloid Leukemia: A Real-Life Cohort Observational Study.","authors":"Fang Cheng, Zheng Cui, Qiang Li, Liu Wang, Weiming Li","doi":"10.2147/BLCTT.S573070","DOIUrl":"10.2147/BLCTT.S573070","url":null,"abstract":"<p><strong>Background: </strong>This study aims to comprehensively evaluate the safety and effectiveness of flumatinib in both first-line and subsequent-line therapies in 244 chronic-phase chronic myeloid leukemia (CML-CP) patients.</p><p><strong>Methods: </strong>Response criteria were applied according to the European LeukemiaNet. Adverse events (AEs) occurring after flumatinib treatment were documented and graded for severity.</p><p><strong>Results: </strong>The study encompassed 244 patients with CML-CP, stratified by treatment lines: first-line (1L, N=138), second-line (2L, N=63), and third-line or above (≥3L, N=43). First-line flumatinib therapy resulted in a major molecular response achieved by 50.7% at 6 months and 66.7% at 12 months, with a deep molecular response (DMR) achieved by 20.3% at 6 months and 35.5% at 12 months. In subsequent treatment lines, those with baseline MR2 had a DMR rate of 42.9%, compared to 23.3% for those without it. Significant differences in molecular response rates were observed based on treatment line and prior tyrosine kinase inhibitors (TKI) resistance (p<0.05). However, subgroup analyses showed no significant differences in treatment responses between the warning and resistance groups after flumatinib therapy. Dose reduction strategies, implemented in 19.3% of patients, have proven feasible without compromising efficacy. Eight patients subsequently attempted treatment cessation, with five maintaining treatment-free remission. AEs were predominantly grade 1-2, with diarrhea (27.0%), fatigue (12.3%), and thrombocytopenia (11.5%) being the most frequent. Grade 3/4 AEs were infrequent, highlighting flumatinib's manageable safety profile.</p><p><strong>Conclusion: </strong>Flumatinib displays significant clinical efficacy and a superior safety profile compared to other second-generation TKI, whether administered in first-line or subsequent treatment settings.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"573070"},"PeriodicalIF":4.9,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Role of Neutrophil Extracellular Traps-Based Risk Model and Discriminative Gene LTF in the Prognosis of Acute Myeloid Leukemia and the Regulation of Immune Microenvironment.","authors":"Yongjian Li, Jingru Zhang, Tingting Liu, Di Zhang, Nana Wang, Xiaomin Liu, Panpan Feng, Juan Zhang, Chunyan Ji, Jingjing Ye","doi":"10.2147/BLCTT.S562651","DOIUrl":"https://doi.org/10.2147/BLCTT.S562651","url":null,"abstract":"<p><strong>Introduction: </strong>Dysregulation of neutrophil extracellular traps (NETs) formation is implicated in cancer progression, coagulation, and metastasis; however, the association with acute myeloid leukemia (AML) prognosis and the immune microenvironment remains poorly understood due to the inherent heterogeneity of NETs. This study aimed to elucidate the role of NETs-related genes in AML pathogenesis, risk stratification, and immune modulation.</p><p><strong>Methods: </strong>We employed comprehensive bioinformatics approaches to analyze NETs-related gene expression profiles from cBioPortal, UCSC Xena, and Gene Expression Omnibus (GEO) databases. A prognostic model was constructed using 16 NETs-related gene signatures, with rigorous validation performed in both internal and external cohorts. Multivariate Cox regression analyses assessed the model's independence as a prognostic indicator for overall survival (OS), and a clinical nomogram was developed for practical application. Additionally, immune cell infiltration and microenvironment characteristics were evaluated through enrichment analyses to correlate NETs activity with immunological features.</p><p><strong>Results: </strong>The NETs-based prognostic model demonstrated robust predictive value for OS in AML patients across validation cohorts and was identified as an independent prognostic factor via multivariate Cox regression. This model enhanced existing risk stratification systems, with high NETs scores significantly associated with neutrophil enrichment and an immunosuppressive tumor microenvironment. Lactotransferrin (LTF) emerged as a pivotal NETs-related gene: its overexpression correlated strongly with adverse prognosis, poor chemotherapy response, and extensive remodeling of the immune landscape, including heightened neutrophil infiltration and immunosuppressive signatures.</p><p><strong>Discussion: </strong>Our comprehensive analysis of NETs in AML suggests that NETs have a role in the tumor microenvironment and prognosis. LTF is a promising candidate biomarker of therapy response and prognostic prediction, which may contribute to individualized clinical decision-making. Further functional validation and prospective clinical studies are warranted to translate our observations into targeted interventions and refine risk-adapted treatment protocols.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"562651"},"PeriodicalIF":4.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Patterns, Temporal Trends, and Potential Non-Infectious Risk Factors for Burkitt Lymphoma from 1990 to 2021.","authors":"Shi-Kai Jin, Jun-Ting Lyu, Zi-Yu Feng, Shu-Qi Zhang, Bin-Yan Lu, Qin-Fu Yan, Jing Li, Jun Du, Zou-Fang Huang","doi":"10.2147/BLCTT.S556459","DOIUrl":"10.2147/BLCTT.S556459","url":null,"abstract":"<p><strong>Background: </strong>The heterogeneity in the health burden and non-infectious risk factors of Burkitt lymphoma (BL) across sex, age, and geographic distribution remain inadequately understood.</p><p><strong>Methods: </strong>Based on Global Burden of Disease study 2021, we estimate the health burden of BL from four metrics: incidence, mortality, prevalence, and disability-adjusted life years. Subgroups were stratified by age, sex, region, and socio-demographic index (SDI). Joinpoint regression was used to evaluate the average annual percentage change (AAPC) to quantify trends in the health burden. Predictions were performed using the Bayesian age-period-cohort model. Non-infectious risk factors were identified and analyzed utilizing summary exposure values (SEVs) to assess their impact on BL incidence and mortality.</p><p><strong>Results: </strong>The estimated global incident number of BL was 19,073 (95% CI: 9651 to 32,509) in 2021, nearly threefold that of 1990. The health burden of BL was markedly higher in males than females, especially among individuals aged under 20 years. From 1990 to 2021, the most significant increasing trend in BL health burden was observed in Cabo Verde, while Georgia exhibited the most notable decline. From 2021 to 2040, the global age-standardized incidence and mortality rates were projected to decline by 14.7% and 24.7%, respectively. Conversely, the health burden on individuals aged 20 to 54 years was anticipated to rise through 2040. In our study, low bone mineral density was found to be linked with elevated risk for males aged over 54 years, while childhood sexual abuse exhibited a paramount positive association with BL risk for females, regardless of age. Notably, tobacco use, particularly secondhand smoking, were inversely associated with BL risk across all age groups and sexes.</p><p><strong>Conclusion: </strong>Burkitt lymphoma demonstrated unique distribution patterns in terms of age, sex, and region. Further investigations into the heterogeneity of the risk factors for BL are essential for the development of more effective health policies and clinical practices.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"556459"},"PeriodicalIF":4.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and Clinical Significance of BCL2 Interacting Protein 3 Like (BNIP3L) in Serum of Patients with MM.","authors":"Yanyu Nong, Zengyi Xiong, Qicai Wang, Mengyuan Gu, Yanting Zheng, Yifan Wang, Jing Wu, Chunni Huang, Zhongqing Li, Jun Luo, Zhian Ling, Ruolin Li","doi":"10.2147/BLCTT.S557238","DOIUrl":"10.2147/BLCTT.S557238","url":null,"abstract":"<p><strong>Background: </strong>BNIP3L regulates mitophagy and apoptosis, and its dysregulation is closely linked to the development and progression of cancers. Studies have shown that BNIP3L is valuable for assessing tumor progression and prognosis. This study aims to investigate the diagnostic and prognostic significance of serum BNIP3L levels in multiple myeloma (MM).</p><p><strong>Methods: </strong>The serum level of BNIP3L were measured in 152 MM patients and 158 healthy controls by Enzyme-Linked Immunosorbent Assay (ELISA). Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic ability of MM. The prognostic relevance of serum BNIP3L levels in MM patients was assessed using Kaplan-Meier survival analysis and Cox regression.</p><p><strong>Results: </strong>Serum BNIP3L levels were significantly elevated in MM patients compared to healthy controls (<i>P</i> < 0.001) and demonstrated significant diagnostic value (Area Under the Curve (AUC) = 0.744). Higher BNIP3L levels correlated negatively with serum calcium (<i>P</i> = 0.02) and M protein (<i>P</i> = 0.03). MM patients with extramedullary infiltration (EMI) or high-risk cytogenetic abnormalities had higher serum BNIP3L levels compared to those without these features (all <i>P</i> < 0.05). BNIP3L levels were significantly higher in non-transplant patients compared to autologous stem cell transplant (ASCT) patients (<i>P</i> = 0.01). And patients achieving Very Good Partial Response (VGPR) efficacy had significantly lower serum BNIP3L levels than those who achieving only Partial Response (PR) (<i>P</i> = 0.04). Compared to patients with low serum BNIP3L levels, those with high levels exhibited a trend toward poorer overall survival (Hazard Ratio (HR) = 1.40, 95%Confidence Interval (CI): 0.47-4.19).</p><p><strong>Conclusion: </strong>This study identified serum BNIP3L as a potential diagnostic biomarker for active MM. Elevated BNIP3L levels were significantly associated with adverse clinical characteristics, suboptimal treatment response, and a trend toward inferior survival. Consequently, measuring serum BNIP3L could be valuable for monitoring disease progression and prognostic evaluation in MM patients.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"15 ","pages":"247-264"},"PeriodicalIF":4.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LRG1 Drives AML Progression by Disrupting Myeloid Progenitor Regulation.","authors":"Rongxia Guo, Peng Wu, Shuxin Yao, Fumei Liu","doi":"10.2147/BLCTT.S556618","DOIUrl":"10.2147/BLCTT.S556618","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) remains clinically challenging due to its molecular heterogeneity and poor outcomes, highlighting the urgent need for novel biomarkers and therapeutic targets.</p><p><strong>Purpose: </strong>This study aims to identify and characterize the role of leucine-rich α-2-glycoprotein 1 (LRG1) in AML, evaluating its potential as both a prognostic biomarker and a therapeutic target.</p><p><strong>Methods: </strong>We conducted an integrated basic and clinical investigation of LRG1 in AML. Methods included analysis of LRG1 expression in patient samples versus controls and pre- versus post-treatment, assessment of its clinical correlations with mutations and subtypes, and evaluation of its prognostic impact. Functional validation was performed using LRG1 knockdown models to assess effects on colony formation, apoptosis, and differentiation. Single-cell RNA profiling was utilized to identify LRG1-enriched cell populations and explore its role in microenvironmental crosstalk.</p><p><strong>Results: </strong>Integrated analysis revealed significantly elevated LRG1 expression in AML patients compared to controls (P<0.001), with levels decreasing post-treatment (P<0.001). High LRG1 expression correlated with FLT3 mutations (P<0.01), M3-M5 AML subtypes (M0&M1&M2 VS M3, P<0.001; M0&M1&M2 VS M4, P<0.01; M0&M1&M2 VS M5, P<0.001; M3 VS M5, P<0.05; M4 VS M5, P<0.05), and worse survival (P<0.01). Functionally, LRG1 knockdown impaired colony formation (P<0.001), increased apoptosis (P<0.001), and disrupted differentiation (P<0.01). Single-cell profiling identified LRG1 enrichment in hematopoietic stem and progenitor cells (HSPCs) and myeloid progenitors, where it facilitated microenvironmental crosstalk via Macrophage Migration Inhibitory Factor (MIF), Galactoside-binding lectin (GALECTIN), and Cyclophilin A (CypA) signals.</p><p><strong>Conclusion: </strong>Our findings establish LRG1 as a robust prognostic biomarker and a key functional regulator of AML maintenance through myeloid progenitor dysregulation, presenting it as a promising target for new therapeutic strategies.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"15 ","pages":"235-246"},"PeriodicalIF":4.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alantolactone Inhibits Double Expression Lymphoma via Dual-Targeted Glycogen Synthase Kinase 3 Beta and B-Cell Lymphoma2.","authors":"Jianhua Chen, Qing Liao, Sha Yang, Jiaojiao Bian, Xianfu Li, Lu Zhao, Dan Wen, Dazhang Bai, Chunlei Yu, Chunyang Zhou, Zhengmin Xu","doi":"10.2147/BLCTT.S556751","DOIUrl":"10.2147/BLCTT.S556751","url":null,"abstract":"<p><strong>Background: </strong>Dual-expression lymphoma (DEL) is an aggressive subtype with concurrent MYC and BCL2 overexpression. This disease exhibits a poor prognosis and responds poorly to standard R-CHOP therapy,highlighting the urgent need for novel treatments. Alantolactone (ALA), a natural compound, has shown anticancer potential, but its efficacy and mechanism in DEL remain unclear. This study aimed to investigate the anti-tumor effects of ALA against DEL and its underlying dual-targeting mechanism.</p><p><strong>Methods: </strong>The cytotoxic activity of ALA was assessed in lymphoma cell lines and a normal lymphocyte line. Apoptosis was evaluated by flow cytometry and Western blotting. Network pharmacology, molecular docking, dynamics simulations, and cellular thermal shift assays (CETSA) were utilized to identify and validate direct targets of ALA. The anti-tumor efficacy of ALA was further examined in a DEL xenograft mouse model using PET-CT imaging and survival analysis.</p><p><strong>Results: </strong>In the present study, the anticancer activity of ALA in DEL was explored in vivo and in vitro. ALA was shown to inhibit DEL growth in vivo with little toxicity to normal tissues. Mechanistically, ALA stabilized active glycogen synthase kinase 3β (GSK3β) (binding affinity: -15.66 kcal/mol; ΔTm +9°C), enhancing β-catenin degradation and suppressing Wnt-driven oncogenesis. Simultaneously, ALA directly bound BCL2 (-22.22 kcal/mol), triggering both intrinsic and extrinsic apoptotic pathways. Simultaneously, ALA directly bound BCL2 (binding affinity: -22.22 kcal/mol), triggering both intrinsic and extrinsic apoptotic pathways. ALA exhibited robust anti-DEL activity across preclinical models. While in vivo it significantly suppressed tumor progression (SUVmax reduction >50%, p<0.01) and extended survival (median 50 vs 80 days, p<0.01) in DEL xenografts. The therapeutic relevance was underscored by clinical correlation showing DEL patients with high GSK3β expression had superior survival outcomes.</p><p><strong>Conclusion: </strong>ALA exerts potent anti-DEL activity by simultaneously targeting GSK3β in the Wnt pathway and directly inhibiting BCL2, leading to suppressed tumor proliferation and induced apoptosis. Our findings highlight ALA as a promising multi-targeting therapeutic candidate for DEL and propose a novel strategy against this refractory lymphoma.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"15 ","pages":"217-233"},"PeriodicalIF":4.9,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase II Trial of an Orelabrutinib-Based Combination Therapy in Newly Diagnosed Primary Central Nervous System Lymphoma.","authors":"Yajing Zhao, Xinguang Liu, Qiang He, Yafei Yu, Lei Xu, Caifeng Sun, Guoqiang Liu, Liang Wang, Ji Ma","doi":"10.2147/BLCTT.S556657","DOIUrl":"10.2147/BLCTT.S556657","url":null,"abstract":"<p><strong>Purpose: </strong>Primary central nervous system lymphoma (PCNSL) is a rare, yet highly aggressive non-Hodgkin lymphoma confined to the central nervous system (CNS). High-dose methotrexate (HD-MTX) remains the baseline chemotherapy for newly-diagnosed PCNSL. Intensive chemotherapies combined with HD-MTX have improved patient outcomes. However, the substantial toxicities limited their applicability, especially among elderly patients with poor physical status. Optimal composition of induction and consolidation treatment are still warranted.</p><p><strong>Patients and methods: </strong>In this prospective single-arm phase II trial (ChiCTR2200061485), we evaluated the efficacy and safety of HD-MTX combined with rituximab and orelabrutinib, a second-generation BTK inhibitor with high CNS penetration, as induction therapy in newly diagnosed PCNSL. Twenty-two patients received up to six cycles of the combined induction therapy. Patients who achieved remission proceeded to non-randomized consolidation therapies with ASCT (autologous hematopoietic stem cell transplantation), WBRT (whole-brain radiotherapy), or orelabrutinib maintenance, based on patient eligibility and physician discretion. The primary endpoint was the centrally assessed response post-induction. Secondary endpoints included progression free survival (PFS), overall survival (OS), and safety.</p><p><strong>Results: </strong>Among the 22 enrolled patients, the overall response rate (ORR) at the end of induction therapy was 91.0%, including 9 patients (41.0%) with complete remissions (CRs), and 11 patients (50.0%) with partial remissions (PRs). With a median follow-up of 22.3 months (range 2.3-42.4 months), the 1-year and 2-year PFS rates were 66.6% and 59.2%, respectively; OS rates were 81.8% and 66.3%, respectively. Consolidation was performed in 15 patients: 5 underwent ASCT, 4 received WBRT, and 6 received maintenance orelabrutinib. The most common adverse effects were grade 1 anemia (45.5%). Grade ≥ 3 events included neutropenia (13.6%) and pneumonia (9.0%).</p><p><strong>Conclusion: </strong>The combination of HD-MTX, rituximab, and orelabrutinib demonstrates high response rates and manageable toxicity in newly diagnosed PCNSL, supporting further evaluation in randomized trials.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"15 ","pages":"203-216"},"PeriodicalIF":4.9,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12691636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venetoclax Plus Blinatumoma as First Line Therapy for Newly Diagnosed Ph-Negative B-Cell Acute Lymphoblastic Leukemia.","authors":"Yutian Lei, Xiaoli Zhao, Huijun Huang, Limin Duan, Ji Xu, Kourong Miao, Huihui Zhao, Chun Qiao, Ming Hong, Sixuan Qian, Lei Fan, Yu Zhu","doi":"10.2147/BLCTT.S556608","DOIUrl":"10.2147/BLCTT.S556608","url":null,"abstract":"<p><strong>Purpose: </strong>This study evaluated the efficacy and safety of a 14-day blinatumomab-venetoclax (BV) regimen as induction therapy for newly diagnosed Ph-negative B-cell acute lymphoblastic leukemia (B-ALL), focusing on rapid remission and tolerability in unfit patients.</p><p><strong>Patients and methods: </strong>Thirteen patients received venetoclax (100 mg on day 1, 200 mg on day 2, 300 mg on day 3, and 400 mg from days 4 to 14) with blinatumomab (9 to 28 ug/day) for 14 days. Bone marrow assessments were performed at days 14-21. Primary endpoints were complete remission (CR) rate, minimal residual disease (MRD) negativity by flow cytometry, and adverse events.</p><p><strong>Results: </strong>The CR rate after one cycle of BV regimen was 92.3% (12/13), and all patients achieved MRD-negativity; 91.7% (11/12) achieved MRD clearance by day 21. Grade 1-2 cytokine release syndrome occurred in 46.2% (6/13; 1 grade 3). Hematologic toxicity included grade 3-4 neutropenia (92.3%) and thrombocytopenia (46.2%), with only 30.8% febrile neutropenia. All AEs resolved rapidly with supportive care, allowing therapy to continue without interruption. At median follow-up of 283 days, 1-year relapse-free survival rate and overall survival rate were 60.6% and 83.3%.</p><p><strong>Conclusion: </strong>The 14-day BV regimen induced rapid deep remission (91.7% MRD-negative by day 21) with manageable toxicity in Ph-negative B-ALL. Synergistic T-cell activation by venetoclax may explain enhanced efficacy.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"15 ","pages":"193-202"},"PeriodicalIF":4.9,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12596882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145490479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Ongoing Challenges of Managing Cytopenic Myelofibrosis in 2025: The Emergence of Non-JAK Inhibitor Therapies.","authors":"Samuel B Reynolds, Rami Komrokji, Andrew T Kuykendall","doi":"10.2147/BLCTT.S549533","DOIUrl":"10.2147/BLCTT.S549533","url":null,"abstract":"<p><p>Primary myelofibrosis (PMF) is a myeloproliferative neoplasm that is felt to arise from somatic mutations with hematopoietic stem and progenitor cells (HSPC's), leading to the development of atypical megakaryocytic hyperplasia. Associated dysregulated cytokine signaling and the trafficking of fibroblasts to the marrow compartment then leads to the deposition of collagen in the marrow compartment. On a molecular level, several well-established driver mutations in <i>JAK2, CALR</i> or <i>MPL</i> activate signaling through JAK/STAT, producing the proliferative phenotype of myelofibrosis. JAK inhibition, accordingly, has been and remains a mainstay in MF-directed therapy. In patients whose disease becomes refractory to Jak inhibitors or in those who experience intolerable adverse effects, however, options from different therapeutic classes are available. Despite this broad availability that includes erythropoiesis-stimulating agents, androgens and TGF-β inhibitors, one of the major challenges in management remains the implementation and successful long-term use of agents to treat cytopenic myelofibrosis. Research into alternative drivers has now led not only to the identification of alternative signaling mechanisms in MF but also to the development and now approval of new therapies outside of Jak inhibitors.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"15 ","pages":"181-192"},"PeriodicalIF":4.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}