Blood and Lymphatic Cancer-Targets and Therapy最新文献

{"title":"A Literature Review of Immunotherapeutics in the Management of Adult B-Cell Acute Lymphoblastic Leukemia.","authors":"Tamer Othman, Ibrahim Aldoss","doi":"10.2147/BLCTT.S630959","DOIUrl":"10.2147/BLCTT.S630959","url":null,"abstract":"<p><p>Relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) has historically been associated with poor outcomes in adults treated with conventional chemotherapy. Allogeneic hematopoietic cell transplantation (HCT) in second remission has been the only strategy associated with durable remissions and potential cure. However, achieving remission after first relapse was challenging in the era predating immunotherapy, and remissions were often brief, frequently limiting the ability to proceed to HCT. Consequently, for decades there has been a critical need for more effective therapeutic approaches in R/R B-ALL. Fortunately, in the last decade, B-ALL has undergone a remarkable therapeutic transformation with the introduction of novel targeted immunotherapies. Blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor (CAR) T-cell therapy have substantially improved patient outcomes in the R/R disease settings while reducing reliance on intensive cytotoxic chemotherapy, and their use has increasingly expanded into the frontline setting as well. This literature review summarizes the pivotal clinical trials supporting the use of blinatumomab, inotuzumab ozogamicin, and CAR T-cell therapies in B-ALL, with a particular focus on their efficacy and toxicity profiles. We also provide our perspective on how these agents can be incorporated into clinical practice and highlight emerging therapeutic agents and strategies. In conclusion, continued advancement and earlier integration of immunotherapeutic approaches could improve long-term outcomes in patients with B-ALL.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"630959"},"PeriodicalIF":3.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963887","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":"Clinical Spectrum, Diagnostic Work-up, and Outcomes of Neurolymphomatosis in Lymphoid Malignancies: A 10-Patient Case Series.","authors":"Safaa Alazzawi, Mohammed Abdulgayoom, Ruba Y Taha, Mohamed Abdelrazek, Wafa M Mohammed, Yahya Mulikandathil, Afaf H Al Battah, Sarah A Elkourashy, Yeslem Ekeibed, Honar Cherif","doi":"10.2147/BLCTT.S633670","DOIUrl":"10.2147/BLCTT.S633670","url":null,"abstract":"<p><strong>Purpose: </strong>Neurolymphomatosis (NL) is a rare infiltration of cranial nerves, nerve roots, plexuses, or peripheral nerves by malignant lymphoid cells. We aimed to describe the clinical spectrum, diagnostic work-up, treatment, and outcomes of NL in a Middle Eastern tertiary cancer center.</p><p><strong>Patients and methods: </strong>We conducted a retrospective single-center case series of patients with clinically and/or radiologically confirmed NL managed at the National Center for Cancer Care and Research, Qatar, from January 2020 to April 2026. Clinical, imaging, cerebrospinal fluid, treatment, response, and survival data were summarized descriptively.</p><p><strong>Results: </strong>Ten patients were identified; median age was 44.5 years, eight were male, eight had B-cell malignancies, and two had T-lymphoblastic leukemia/lymphoma. Three had synchronous NL at initial diagnosis, whereas seven developed NL with relapsed, refractory, or recurrent disease. MRI supported NL in 7/10 patients, cerebrospinal fluid in 4/10, and PET/CT in 3/10; none underwent direct nerve biopsy. Best neurologic response was complete in three patients, partial in four, and absent in three. Four patients were alive at censoring, and six had died of progressive disease.</p><p><strong>Conclusion: </strong>In this regional cohort, NL usually occurred with aggressive active disease and showed heterogeneous neurologic presentations. Diagnosis depended on integrating clinical findings with MRI, PET/CT, and cerebrospinal fluid studies. Although overall outcomes were poor, durable disease control was achieved in selected patients. Multicenter studies are needed to refine diagnostic pathways and treatment strategies.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"633670"},"PeriodicalIF":3.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897869","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":"Efficacy and Safety of CLAG-Based Sequential Conditioning Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Non-Remission Relapsed or Refractory Acute Leukemia.","authors":"Shiyu Chen, Xiaohan Zhang, Xiaoqing Li, Xin Du","doi":"10.2147/BLCTT.S601808","DOIUrl":"10.2147/BLCTT.S601808","url":null,"abstract":"<p><strong>Background: </strong>The optimal bridge-to-transplant strategy for patients with relapsed or refractory (R/R) acute leukemia who remain in non-remission (NR) is undefined. We evaluated the strategy-level use of CLAG (cladribine, cytarabine, and granulocyte colony-stimulating factor) as part of sequential conditioning, rather than as stand-alone salvage therapy, before allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><strong>Methods: </strong>This single-center retrospective case series included nine consecutive patients with R/R acute leukemia and bone marrow blasts ≥10% who underwent CLAG-based sequential conditioning followed by allo-HSCT between January 2021 and July 2023. Engraftment, transplant-related complications, non-relapse mortality, relapse, disease-free survival (DFS), and overall survival (OS) were evaluated descriptively; no control group was available.</p><p><strong>Results: </strong>All nine patients achieved neutrophil and platelet engraftment and complete donor chimerism at approximately day +30. At a routine MFC/NGF analytical sensitivity of 10^-4, all patients had negative bone marrow assessments at day +30 and month +3; abnormal/leukemic cells subsequently re-emerged in all five patients who relapsed, at months 4.1-9.8. Seven of nine patients (77.8%) developed infections during neutropenia, including one severe pulmonary infection with probable Aspergillus that improved with antifungal therapy. GVHD occurred in 3/9 patients (33.3%), and hemorrhagic cystitis occurred in 2/9 (22.2%). No non-relapse mortality occurred. Five patients (55.6%) relapsed, and all five deaths were relapse-related. Estimated 2-year DFS and OS were both 44.4% (95% confidence interval, 13.6-71.9%).</p><p><strong>Conclusion: </strong>In this highly selected cohort of nine NR patients, CLAG-based sequential conditioning permitted engraftment without non-relapse mortality, but infection and relapse remained frequent. These findings support technical feasibility only and should be regarded as exploratory and hypothesis-generating; efficacy or superiority cannot be established without larger prospective, multicenter, controlled studies.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"601808"},"PeriodicalIF":3.2,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654718","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":"Long-Term Results of Busulfan Plus High-Dose Idarubicin as a Conditioning Regimen to Autologous Stem Cell Transplantation Following Cytarabine Consolidation in Young Patients with Favorable or Intermediate-Risk Acute Myeloid Leukemia.","authors":"Zixing Lu, Yayi Liu, Zhaoqing Jiang, Yu Zhu, Wenjie Liu, Qian Sun, Lei Fan, Sixuan Qian, Ming Hong","doi":"10.2147/BLCTT.S621412","DOIUrl":"10.2147/BLCTT.S621412","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the long-term efficacy and safety of high-dose idarubicin plus busulfan (I-Bu) conditioning followed by autologous stem cell transplantation (ASCT) compared to intermediate- to high-dose cytarabine (Ara-C) consolidation in young acute myeloid leukemia (AML) patients with favorable- or intermediate-risk in first complete remission (CR₁).</p><p><strong>Methods: </strong>We retrospectively analyzed clinical data from 59 young AML patients (aged ≤ 65 years) with favorable- or intermediate-risk disease who received the I-Bu conditioning regimen followed by ASCT between December 2004 and December 2021 (ASCT group). Clinical outcomes were compared with 57 favorable- and intermediate-risk AML patients treated with intermediate- to high-dose Ara-C consolidation chemotherapy alone (chemotherapy group). Overall survival (OS) and disease-free survival (DFS) were evaluated, and univariate and multivariate analyses were performed to identify prognostic factors associated with OS.</p><p><strong>Results: </strong>A total of 116 patients were included with a median follow-up of 79.5 months. Median OS was not reached in either group. The ASCT group achieved a significantly higher 2-year OS rate (84.5% vs 59.7%, <i>P</i>=0.0018) and sustained a significant OS benefit in the 10-year OS rate (<i>P</i>=0.0017). DFS rate also showed superiority in the ASCT group at 2-year (77.7% vs 53.5%, P=0.0037) and maintained this benefit in the 10-year DFS rate (<i>P</i>=0.0038). Multivariate Cox regression identified treatment modality as an independent prognostic factor for OS (HR = 3.12, 95% CI: 1.48-6.59, <i>P</i>=0.0028). In subgroup analysis, ASCT significantly improved OS (<i>P</i><0.001) and DFS (<i>P</i>=0.0014) in favorable-risk patients, whereas no differences were observed in intermediate-risk patients (OS, <i>P</i>=0.13; DFS, <i>P</i>=0.21).</p><p><strong>Conclusion: </strong>The I-Bu conditioning regimen followed by ASCT provides durable survival benefits and a favorable safety profile for young, favorable-risk AML patients in CR₁, representing a potential post-remission therapeutic option. Its role in intermediate-risk AML requires further validation.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"621412"},"PeriodicalIF":3.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13381044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521045","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":"Risk and Survival Outcomes of Secondary Primary Malignancies in Chinese Lymphoma Patients in the Era of Modern Targeted Therapies: A Single-Center Retrospective Cohort Study.","authors":"Chen Qiu, Tingting Zhang, Xuejing Yang, Yafang Guo, Zihui Gong, Dong Song","doi":"10.2147/BLCTT.S616235","DOIUrl":"10.2147/BLCTT.S616235","url":null,"abstract":"<p><strong>Introduction: </strong>With the advent of modern therapies, including rituximab and novel oral targeted agents such as BTK inhibitors, the survival of lymphoma patients has significantly improved. However, the risk of secondary primary malignancies (SPMs) remains a critical concern. This study aims to evaluate the incidence, risk factors, latency, and survival outcomes of SPMs in lymphoma patients treated in the era of targeted therapies.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted on 1,715 lymphoma patients diagnosed between October 2011 and October 2024 at Shanxi Bethune Hospital, China. Patients with incomplete records, pediatric cases, or immunodeficiency were excluded. Data on demographics, lymphoma characteristics, treatment modalities, and SPMs were collected. SPMs were classified as synchronous (diagnosed within 6 months of lymphoma) or metachronous (diagnosed after 6 months). Statistical analyses included Cox regression for risk factors and Kaplan-Meier for survival analysis.</p><p><strong>Results: </strong>Among 1,715 lymphoma patients, 65 (3.8%) developed SPMs, including 10 synchronous (0.6%, descriptive enumeration only), while 55 (3.2%) developed metachronous SPMs that constituted the primary analytic cohort. Aggressive B-cell non-Hodgkin lymphoma (43.6%) was the most common lymphoma subtype among patients who developed SPMs, followed by indolent B-cell non-Hodgkin lymphoma (38.2%). Digestive and respiratory system tumors were the predominant SPMs (34.5% and 23.6%, respectively). Multivariate analysis identified male sex, ECOG performance status ≥2, extranodal involvement, bone marrow infiltration, BTK inhibitor use, and radiotherapy as independent risk factors for SPMs. Competing-risk analysis showed a higher cumulative incidence of SPMs in patients exposed to BTK inhibitors than in those not exposed to BTK inhibitors (5-year CIF, 7.92% vs 2.57%; Gray's test [Formula: see text] =0.007). Kaplan-Meier analysis showed that patients with SPMs had significantly worse OS than those without SPMs (median OS, 10.3 years; 5-year OS, 69.6% vs 89.6%; log-rank [Formula: see text]<0.0001). No significant difference in OS was observed between patients with solid and hematologic SPMs (median OS, 12.8 vs 6.0 years; [Formula: see text]=0.76).</p><p><strong>Discussion: </strong>In the transitional era of conventional and targeted therapies, although data are limited.This exploratory analysis confirmed that gastrointestinal and respiratory SPMs predominated in this Asian cohort, and identified male sex, ECOG ≥2, extranodal involvement, bone marrow infiltration, radiotherapy, and BTK inhibitor use as independent risk factors. The association with BTK inhibitors (HR=2.56) warrants cautious interpretation and prospective validation. Early detection and tailored surveillance (prioritizing gastrointestinal screening) are essential for improving long-term outcomes.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"616235"},"PeriodicalIF":3.2,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498168","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":"Metabolic Subtypes Predict Treatment Response in Acute Myeloid Leukemia: A Pilot Study.","authors":"Changjian Yan, Yan Huang, Qing Cai, Xiang Li, Qinwen Yang, Gang Feng, Huilin Yang, Yanxin Chen, Jianda Hu","doi":"10.2147/BLCTT.S612305","DOIUrl":"10.2147/BLCTT.S612305","url":null,"abstract":"<p><strong>Introduction: </strong>To establish a dynamic metabolic subtyping system for acute myeloid leukemia (AML) based on longitudinal metabolomics and multi-omics integration, and to evaluate its ability to predict treatment response.</p><p><strong>Methods: </strong>We enrolled 29 AML patients and performed untargeted metabolomics on pre‑ and post-treatment serum samples. Based on finite cyclic combinations of metabolic pathways, pre-treatment patients were classified into G1 (glycolysis/gluconeogenesis/TCA cycle) and G2 (fatty acid/folate biosynthesis). Post‑treatment patients were categorized into TG1 (α-linolenic acid metabolism, pantothenate/CoA biosynthesis) and TG2 (purine metabolism, cysteine/methionine metabolism). Baseline transcriptome data were integrated and validated in three external cohorts (Beat2, GSE6891, GSE37642; total n=994). Single cell and spatial transcriptomics were used to investigate cellular heterogeneity and resistance mechanisms.</p><p><strong>Results: </strong>The complete remission (CR) rate was significantly higher in G2 (71%) than in G1 (29%). After treatment, TG2 showed an 83% CR rate versus 17% in TG1. All patients transitioning from G2 to TG2 achieved CR (100%), whereas those from G1 to TG2 maintained poor response. Baseline metabolic subtype was an independent predictor of treatment response (p<0.05). To explore candidate cellular niches linking G1 metabolic features to chemotherapy resistance, we further integrated single-cell and spatial transcriptomic analyses. The results revealed co-localization of CA2-high immature erythrocytes and neutrophils in non-CR patients.</p><p><strong>Discussion: </strong>Dynamic metabolic subtyping (G1/G2, TG1/TG2) strongly correlates with AML treatment response. The co-localization of CA2-high immature erythrocytes and neutrophils in the bone marrow microenvironment of non-CR patients provides a candidate cellular and microenvironmental correlate of the G1 metabolic phenotype, suggesting a mechanistic link between systemic metabolic reprogramming and chemotherapy resistance. Collectively, these findings highlight the potential of combining dynamic metabolic subtyping with identified microenvironmental features to guide precision therapy.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"612305"},"PeriodicalIF":3.2,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148296742","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":"A Risk Model Using Refined Disease Risk Index and 1-Month NK-Cell Count for Relapse in Children and Adults with T-ALL/LBL After Myeloablative Umbilical Cord Blood Transplantation.","authors":"Na Zhao, Rong Chi, Kaidi Song, Yue Wu, Bingbing Yan, Dongyao Wang, Baolin Tang, Xiaoyu Zhu","doi":"10.2147/BLCTT.S582933","DOIUrl":"10.2147/BLCTT.S582933","url":null,"abstract":"<p><strong>Purpose: </strong>To assess transplant outcomes after umbilical cord blood transplantation (UCBT) in patients with T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) and identify factors associated with relapse.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed 105 patients with T-ALL/LBL (age, 2-53 years), who underwent single-unit UCBT as their first transplant at our center between January 2014 and June 2024. Transplant outcomes were assessed in the overall cohort. Relapse-associated factors were identified using Fine-Gray competing-risk regression in the subgroup with available 1-month peripheral blood natural killer (NK) cell measurements (58/105, 55.2%). The 1-month NK-cell count was dichotomized based on the median number in the analyzed cohort. A simplified risk score was derived from the final multivariable model. Model performance was assessed using time-dependent area under the curve (AUC) and calibration analysis.</p><p><strong>Results: </strong>In the overall cohort, the 3-year overall survival, progression-free survival, and GVHD-free relapse-free survival were 57.3% (95% CI, 46.9-66.4%), 54.9% (95% CI, 44.9-63.9%), and 49.3% (95% CI, 39.5-58.5%), respectively, and the 3-year cumulative incidence of relapse was 34.5% (95% CI, 25.5-43.6%). In the NK-measured subgroup, multivariable Fine-Gray analysis identified high refined Disease Risk Index (R-DRI) (sHR, 4.561; 95% CI, 1.662-12.51; <i>P</i> = 0.003) and low 1-month NK-cell count (< 0.165 × 10⁹/L) (sHR, 6.175; 95% CI, 1.711-22.280; <i>P</i> = 0.005) as independent factors associated with relapse. A 2-point score stratified patients into low-, intermediate-, and high-risk groups with 3-year relapse incidences of 0, 43.5% (95% CI, 23.3-62.1%), and 89.7% (95% CI, 48.6-98.4%), respectively (<i>P</i> < 0.001). The apparent 3-year AUC was 0.539 (95% CI, 0.255-0.823), and the optimism-corrected AUC was 0.523.</p><p><strong>Conclusion: </strong>Relapse remains a major cause of treatment failure after UCBT in T-ALL/LBL. High R-DRI and low 1-month NK-cell count were independently associated with relapse and allowed apparent risk stratification in the development cohort. This exploratory 2-factor model may provide a basis for future studies of relapse assessment incorporating early immune recovery.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"582933"},"PeriodicalIF":3.2,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13207877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148044170","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":"Exploring the Bone Marrow Microenvironment as a Therapeutic Barrier and Targetable Source of Crosstalk in Acute Myeloid Leukemia.","authors":"Aleksandra Kolosova, Imogen Anna Mould, Chris Pepper, Simon Mitchell, Andrea G S Pepper, Eleni E Ladikou, Fabio A Simoes","doi":"10.2147/BLCTT.S511758","DOIUrl":"10.2147/BLCTT.S511758","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is an aggressive and genetically heterogeneous hematological malignancy characterized by the accumulation of immature myeloid blasts that disrupt healthy hematopoiesis. Despite advances in molecular profiling and targeted therapies, overcoming drug resistance and relapse remains a significant clinical challenge, resulting in poor long-term outcomes. Crucially, disease persistence is sustained not merely by intrinsic genetic lesions but by a highly adaptive bone marrow microenvironment (BMME) that functions as a therapeutic barrier. While the healthy niche tightly regulates hematopoietic stem cell maintenance, leukemic blasts co-opt stromal, vascular, and immune components to establish a sanctuary that fuels proliferation and shields the disease from cytotoxic stress. However, dissecting these reciprocal dependency mechanisms uncovers critical vulnerabilities, presenting a vital opportunity to develop novel targeted therapies. In this review, we discuss the architecture of the healthy BMME and its pathological AML-driven remodeling. We describe the role of specific signaling axes that govern AML-BMME crosstalk and evaluate targeted therapeutic strategies designed to uncouple these protective interactions. Finally, we highlight that current preclinical models lack the complexity of the BMME stromal components and its spatial organization, a limitation that continues to hinder clinical translation and delay the development of effective combination therapies.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"511758"},"PeriodicalIF":3.2,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13200207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148036164","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":"Short-Term Longitudinal Analysis of Gut Microbiota Dynamics During Anti-CD19 CAR-T Cell Therapy in Diffuse Large B-Cell Lymphoma Patients.","authors":"Ziyuan Shen, Xing Xing, Kang Rong, Ziyang Geng, Ning Yang, Linyan Xu, Hongfeng Ge, Wei Sang","doi":"10.2147/BLCTT.S598958","DOIUrl":"10.2147/BLCTT.S598958","url":null,"abstract":"<p><strong>Purpose: </strong>Alterations in gut microbiota may influence immune response and treatment outcomes in patients with diffuse large B-cell lymphoma (DLBCL). However, the dynamics during anti-CD19 CAR-T cell therapy remain unclear.</p><p><strong>Methods: </strong>We conducted a short-term longitudinal microbiome analysis in DLBCL patients (n=12) undergoing CAR-T cell therapy targeting CD19. Stool samples were collected at baseline, 1 week, and 2 weeks post-infusion. 16S rRNA gene sequencing was used to assess microbial diversity, taxonomic composition, and functional pathways. Correlation analyses were then conducted between microbial taxa and inflammatory biomarkers.</p><p><strong>Results: </strong>Alpha diversity indices showed no statistically significant differences across time points. Beta diversity analysis revealed distinct clustering between baseline and week 1 samples in sPLS-DA, although PERMANOVA did not reach statistical significance. At the phylum level, Bacteroidota abundance significantly increased at week 2 compared with baseline (<i>P</i> = 0.008), accompanied by a marked reduction in the Firmicutes/Bacteroidota ratio. Genus-level heatmap and LEfSe analysis identified enrichment of <i>Parabacteroides</i>, and <i>Prevotella</i> at week 2, whereas baseline samples were enriched in Clostridium sensu stricto 13 and <i>Fusobacterium</i>. Functional prediction indicated that lipoic acid metabolism pathways were significantly upregulated at weeks 1 and 2 compared with baseline (both <i>P</i> < 0.05). Correlation analysis demonstrated that specific bacterial taxa, including <i>Parabacteroides</i> and <i>Prevotella</i>, were positively associated with lymphocyte counts and inversely correlated with C-reactive protein levels.</p><p><strong>Conclusion: </strong>Gut microbiota alterations following CAR-T infusion, characterized by increased Bacteroidota abundance, specific taxonomic shifts, and enhanced lipoic acid metabolism, may provide early microbial signatures for monitoring immune modulation in DLBCL patients.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"598958"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844369","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":"Poor Outcome of Pediatric Patients with Acute Lymphoblastic Leukemia Harboring Low P16 Deletion Ratio: A Post-Hoc Analysis from a Prospective Cohort.","authors":"Kun-Yin Qiu, Xiong-Yu Liao, Hai-Lei Chen, Hong Zheng, Jian-Pei Fang, Dun-Hua Zhou","doi":"10.2147/BLCTT.S592290","DOIUrl":"10.2147/BLCTT.S592290","url":null,"abstract":"<p><strong>Object: </strong>The prognostic significance of <i>P16 (CDKN2A)</i> deletion (<i>P16^del</i> ) in pediatric acute lymphoblastic leukemia (ALL) remains controversial, potentially due to the historical reliance on binary classification.</p><p><strong>Methods: </strong>In this prospective cohort study (SCCLG-ALL-2016 protocol), we analyzed 413 pediatric ALL patients. <i>P16^del</i> status and ratio were quantified using standardized FISH. Statistical models adjusting for key prognostic factors were performed. Piecewise linear regression identified prognostic thresholds for <i>P16^del</i> ratio. Survival outcomes (relapse-free survival, RFS; overall survival, OS) and interactions with minimal residual disease (MRD) were assessed.</p><p><strong>Results: </strong><i>P16^del</i> prevalence was 18.2% (75/413). Multivariable analysis confirmed <i>P16^del</i> as an independent adverse prognostic factor (RFS: <i>HR</i>=2.2, <i>p</i>=0.020; OS: <i>HR</i>=2.7, <i>p</i>=0.024). Crucially, a nonlinear dose-response relationship identified 0.8 as the critical <i>P16^del</i> ratio threshold: Below 0.8, each unit ratio increase conferred a 93% higher relapse/death risk (adjusted Log<i>HR</i>=1.93, <i>p</i>=0.031); above 0.8, higher ratios reduced risk by 33% (adjusted Log<i>HR</i>=0.67, <i>p</i>=0.048). Patients with low ratios (<0.8, n=37) had significantly inferior 5-year outcomes (RFS: 57.7%, OS: 72.2%) compared to high ratios (≥0.8, n=38; RFS: 88.5%, OS: 94.7%) (<i>p</i><0.001). The prognostic impact of MRD was critically dependent on <i>P16^del</i> ratio: Low ratio with D33 MRD+ predicted catastrophic outcomes (5-year RFS=27.8%), while high ratio patients maintained excellent survival regardless of MRD status (D33 MRD+ RFS=100%). High-ratio patients exhibited enrichment for RAS mutations (<i>p</i>=0.046).</p><p><strong>Conclusion: </strong>The identified P16 deletion ratio threshold of 0.8 may guide precision risk-adapted therapy in pediatric ALL, but its clinical utility must be validated in larger, diverse cohorts before implementation.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"592290"},"PeriodicalIF":3.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844396","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}