Hematological Oncology最新文献

{"title":"Metabolic Tumor Area: A Clinically Practical Prognostic Marker for Improved Risk Stratification in IPI Non-High-Risk DLBCL","authors":"Silu Cui,&nbsp;Qi Jiang,&nbsp;Faquan Ji,&nbsp;Panpan Luan,&nbsp;Yuxiao Hu,&nbsp;Yu Zhang","doi":"10.1002/hon.70243","DOIUrl":"10.1002/hon.70243","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Metabolic tumor volume (TMTV) is a core ¹⁸F-FDG PET/CT prognostic marker for diffuse large B-cell lymphoma (DLBCL), but its complex measurement and limited standardization restrict clinical utility. Metabolic tumor area (MTA) features simple operation and good reproducibility, holding potential as a practical alternative to TMTV. This retrospective study aimed to validate MTA's substitutability and explore its prognostic value in DLBCL risk stratification. A total of 295 newly diagnosed DLBCL patients were enrolled. TMTV and MTA were measured via semi-automatic segmentation (41% SUVmax threshold). Survival analysis, Cox regression, 5-fold cross-validation, and time-dependent ROC curves were used to evaluate prognostic performance. Multivariate analysis revealed MTA, rather than TMTV, independently predicted progression-free survival (PFS) and overall survival (OS) (all <i>p</i> &lt; 0.05), with stability confirmed by cross-validation. The combined MTA and <i>D</i>_max model provided IPI-independent prognostic value, and exhibited improved predictive capacity compared with conventional IPI and TMTV and <i>D</i>_max model in non-high-risk IPI patients (all <i>p</i> &lt; 0.05). It successfully identified occult high-risk subgroups that were undetectable by standard IPI grading. MTA possesses favorable prognostic performance and may serve as a practical alternative to TMTV for DLBCL assessment. The MTA and <i>D</i>_max model complements the traditional IPI system, facilitating refined risk stratification and individualized clinical management. Further validation in multi-center prospective cohorts is warranted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial registration</h3>\u0000 \u0000 <p>Ethics Committee of Jiangsu Cancer Hospital (Approval KY-2025-095, 16 July 2025)</p>\u0000 </section>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808376","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}

{"title":"Epigenetic Rewiring and Context-Dependent Therapeutic Vulnerabilities in Myeloproliferative Neoplasms","authors":"Amr Ali Mohamed Abdelgawwad El-Sehrawy,&nbsp;Mutaz Jamal Al-khreisat,&nbsp;Aziz Kubaev,&nbsp;Adilbek Rajapov,&nbsp;Sajida Hussein Ismael,&nbsp;Bahjat Alhasso,&nbsp;Irwanjot Kaur,&nbsp;Neeraj Bainsal","doi":"10.1002/hon.70239","DOIUrl":"https://doi.org/10.1002/hon.70239","url":null,"abstract":"<div>\u0000 \u0000 <p>Myeloproliferative neoplasms (MPN) are shaped by epigenetic rewiring that extends beyond canonical JAK2V617F-driven signaling. This review argues that context-dependent chromatin states, not merely genetic lesions, determine disease trajectory, fibrotic transformation, and leukemic progression. We synthesize recent evidence indicating that PRC2 deficiency is supported by the strongest MPN-specific evidence for BRD4 dependency, whereas PARP/BCL-2 vulnerabilities associated with TET2/IDH mutations and USP7 dependency associated with ASXL1 remain supported primarily by related myeloid malignancies or preclinical studies. Introducing the concept of an “epigenetic clock” of clonal evolution, we propose that MPN cells acquire progressively pathological chromatin states that can be quantified through composite methylation and accessibility scores. Importantly, temporal synthetic lethality, using short epigenetic pulses to remodel chromatin before applying targeted agents, offers a rational scheduling strategy to expose non-redundant dependencies while sparing normal hematopoiesis. We outline a translational roadmap incorporating cfDNA methylome biomarkers, ongoing BET inhibitor trials, and emerging single-cell perturbation approaches. Finally, we highlight the “dark epigenome” of repetitive elements as an unexplored therapeutic frontier. Collectively, these findings suggest that context-restricted chromatin vulnerabilities may offer therapeutic opportunities for disease-modifying intervention in progression-prone MPN clones.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784941","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}

{"title":"Circulating Tumor DNA and Immune Response Markers for Improved Treatment Outcome Prediction in Diffuse Large B-Cell Lymphoma: A Scoping Review","authors":"Ailin McMahon,&nbsp;Elizabeth J. Ryan,&nbsp;Sarah Dillon,&nbsp;Ruth Clifford","doi":"10.1002/hon.70242","DOIUrl":"https://doi.org/10.1002/hon.70242","url":null,"abstract":"<p>Early identification of refractory disease remains a significant unmet clinical need in patients with diffuse large B-cell lymphoma (DLBCL). This scoping review was conducted to assess the current knowledge on the use of circulating tumor DNA (ctDNA), either alone or in combination with immune markers, as predictive tools for treatment outcome in previously untreated DLBCL patients. A systematic search of online databases PubMed, Embase, CINAHL, and Cochrane was performed from inception to May 2025. This focused on primary research studies investigating the use of ctDNA or immune markers to assess treatment response and predict outcomes in DLBCL. 61 publications were selected for inclusion. The key points of interest for this scoping review were: pre-analytical sample handling, laboratory methodologies—including sequencing panels and platforms; and mutations or immune markers associated with prognosis or patient outcome. Strong evidence supports the utility of ctDNA analysis at key timepoints to evaluate treatment response: diagnosis, cycle 2 day 1, cycle 3 day 1, and end of treatment. ctDNA assays with adequate sensitivity can improve interpretation of FDG¹⁸-PET/CT scans, reducing unnecessary additional testing for patients. Molecular clustering on ctDNA also improves risk stratification. Elevated cytokines such as CXCL10 and IL-10 and elevated numbers of myeloid derived suppressor cells in pre-treatment samples are associated with inferior prognosis. ctDNA analysis shows promise in improving outcomes for patients with DLBCL. Assay standardization for ctDNA analysis is currently lacking. Further investigation into the additional value of immune marker analysis is required. This includes understanding the association between immune markers and molecular subgroups identified on ctDNA analysis.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venetoclax in Combination With Chemo-Immunotherapy in Richter Transformation: A Real-Life Experience","authors":"L. Ballotta,&nbsp;J. Olivieri,&nbsp;D. Facchinelli,&nbsp;I. Ferrarini,&nbsp;A. Visentin,&nbsp;R. Moia,&nbsp;M. Cavallari,&nbsp;V. Innao,&nbsp;E. Derenzini,&nbsp;P. M. Nierychlewska,&nbsp;A. Cuda,&nbsp;V. Gattei,&nbsp;M. Ballerini,&nbsp;E. Lucchini,&nbsp;M. Turoldo,&nbsp;M. C. Rossetti,&nbsp;F. Gaudio,&nbsp;F. Zaja","doi":"10.1002/hon.70223","DOIUrl":"https://doi.org/10.1002/hon.70223","url":null,"abstract":"<div>\u0000 \u0000 <p>The prognosis of Richter Transformation (RT) with standard chemo-immunotherapy (CIT) remains poor. Several previous experiences with Venetoclax (V) in combination with CIT demonstrated the feasibility and safety of V-CIT based regimens in RT. This is a retrospective, observational multicenter study aimed to assess the efficacy and safety of the <i>real-life</i> use of V-CIT in the treatment of RT. Response assessments were evaluated according to the Lugano 2014 criteria. 20 consecutive patients treated with V-CIT based regimens from October 2018 to July 2024, were included. Median age was 63.5 years (33–73), with 75% of males. 11/17 were IGHV unmutated and 8/18 carried a mutation for Tp53 and/or a del17p. The median time from CLL diagnosis to RT was 6.5 years (0–17). A clonal relationship was demonstrated in 16/16 evaluable patients. The median number of prior treatments for CLL was 2 (0–4): CIT in 10, BTKi in 10, V based treatment in 4, no previous therapy in 5. V was associated with R-DA-EPOCH, R-CHOP, and BFM in 10, 9 and 1 patients for a median number of 4 cycles (1–6). ORR was 55% with 10 CR (50%) and 1 PR (5%). 3 patients had progressive disease (PD) and 1 died for multiorgan failure. 7 patients received allogeneic-HSCT consolidation. At a median follow up of 11.5 months (1–78), 10 patients, including 5 who received HSCT, are alive in CR; median PFS and OS were not reached. All patients experienced grade 3-4 hematological toxicities: neutropenia (100%), anemia (50%) and thrombocytopenia (25%). Non-hematological toxicities included: febrile neutropenia (15%), covid19 (25%), other infections (30%), nausea (10%), thrombotic/hemorrhagic events (10%). Data from this <i>real-life</i> experience confirm the feasibility and the activity of V-CIT based combination in younger fit RT patients, where the high rate of initial response may allow a significant proportion to receive allogeneic-HSCT consolidation. New studies with V combinations are ongoing and the comparison with this <i>real-life</i> data may be worthwhile to better understand their therapeutic impact.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784122","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}

{"title":"Langerhans Cell Histiocytosis in Adults: A Canadian Multicenter Case Series","authors":"Stephanie Quon,&nbsp;Yaswanta Gummadi,&nbsp;Ibrahim Elsharawi,&nbsp;Jessica Dobson,&nbsp;Mariam Goubran,&nbsp;Ryan J. Stubbins,&nbsp;Eli L. Diamond,&nbsp;Luke Y. C. Chen","doi":"10.1002/hon.70241","DOIUrl":"10.1002/hon.70241","url":null,"abstract":"<p>Langerhans cell histiocytosis (LCH) is a rare clonal myeloid neoplasm. Canadian data on clinical characteristics, molecular profile, and treatment outcomes is limited. This study aims to report the initial experience of a Canadian rare diseases program, reflecting “real-world” diagnostic pathways, referral patterns, and treatment heterogeneity across multiple provinces. We conducted a retrospective review of patients managed in an adult-care cohort with histologically confirmed LCH diagnosed between 2000 and 2025 across multiple Canadian centers. Patients diagnosed as children and subsequently transferred to adult care were included. Clinical features, radiologic findings, histopathology, molecular testing, treatment approaches, and outcomes were collected and analyzed. Thirty-one patients were identified, with a median age at diagnosis of 42 years (range: 2–84) and a male predominance (65%). Bone (74%), lung (29%), and skin (16%) were the most commonly involved sites. Concomitant or subsequent malignancies were present in 19% of patients. Molecular testing found BRAFV600E mutations in 44% of tested patients. The most common first-line systemic therapy was cytarabine (<i>n</i> = 10), followed by other drugs such as hydroxyurea, vemurafenib, and cladribine. This series represents the initial experience of a Canadian rare disease referral program and captures the clinical heterogeneity and longitudinal adult care of patients with LCH across multiple provinces. Variability in treatment approaches highlights the need for collaborative prospective natural history studies and coordinated clinical trials.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Transformation of the Microenvironment: From Observer to Coordinator in Monoclonal Gammopathy of Undetermined Significance (MGUS) to Myeloma Development","authors":"Amr Ali Mohamed Abdelgawwad El-Sehrawy,&nbsp;Abeer Jabra Shnoudeh,&nbsp;Ilkhom Yuldashev,&nbsp;Dildora Jalilova,&nbsp;Zebiniso Alimova,&nbsp;Rajashree Panigrahi,&nbsp;Rswl Mahmoud Hashem,&nbsp;Neeraj Bainsal","doi":"10.1002/hon.70240","DOIUrl":"10.1002/hon.70240","url":null,"abstract":"<div>\u0000 \u0000 <p>Monoclonal gammopathy of undetermined significance (MGUS) is a common asymptomatic plasma cell disorder and the major precursor state of multiple myeloma (MM). Although progression is partly shaped by intrinsic genetic and epigenetic changes within the plasma cell clone, increasing evidence indicates that the bone marrow microenvironment plays a decisive role in determining whether the clone remains clinically silent or evolves toward symptomatic disease. This review examines how the marrow niche changes across the MGUS–SMM–MM continuum. In early MGUS, the microenvironment may already be permissive, but it remains partly restrained: immune control is not fully lost, stromal activation is incomplete, vascular remodeling is limited, and the bone-remodeling compartment has not yet become overtly tumor-supportive. Progression appears to occur when these initially modest stromal, vascular, skeletal, immune, and extracellular matrix alterations become functionally connected. Once linked, these changes form reinforcing circuits that enhance plasma cell retention and survival, weaken immune containment, remodel the vascular and skeletal niche, and promote resistance to therapy. In this view, MGUS-to-MM progression is not simply a plasma cell–autonomous process, but a gradual ecological shift in which the marrow niche becomes increasingly aligned with the needs of the malignant clone. Understanding this coordinated microenvironmental remodeling may improve risk stratification and support therapeutic strategies that target both the plasma cell clone and its supportive niche.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758953","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}

{"title":"Allogeneic Stem Cell Transplantation—A Salvage Option for High-Risk Chronic Lymphocytic Leukemia Patients: A 15-Year Single-Center Experience","authors":"Natalia B. Mikhailova,&nbsp;Maria I. Kislova,&nbsp;Maria O. Ivanova,&nbsp;Julia A. Zhuravleva,&nbsp;Elena A. Dmitrieva,&nbsp;Elena V. Kondakova,&nbsp;Anna G. Smirnova,&nbsp;Yana V. Krylova,&nbsp;Olga V. Kudyasheva,&nbsp;Yulia Y. Vlasova,&nbsp;Anastasya V. Beynarovich,&nbsp;Nikita P. Volkov,&nbsp;Ivan S. Moiseev,&nbsp;Eugene A. Nikitin,&nbsp;Alexander D. Kulagin","doi":"10.1002/hon.70229","DOIUrl":"10.1002/hon.70229","url":null,"abstract":"<div>\u0000 \u0000 <p>The role of allogeneic hematopoietic cell transplantation (alloSCT) in chronic lymphocytic leukemia (CLL) has decreased in recent years due to the emergence of new effective targeted agents for the treatment of this disease. However, for a certain group of heavily pretreated or high-risk CLL patients with no other therapeutic options, allo-SCT remains important. Due to the fact that in most high-risk CLL patients it is possible to achieve durable response as a result of Bruton's tyrosine kinase inhibitors (ВТК), BCL-2 inhibitor and especially in their combined application, including in the first line of therapy, the choice of time point for alloSCT becomes relevant. In this retrospective study allo-SCT was performed in 44 patients with the period from 2006 to 2023. Progression-free survival was 79.2% at 12 months and 69.3% at 24 months. Similarly, overall survival was 81.4% at 12 months and 74% at 24 months. Graft—versus-host disease relapse-free survival was 57%. Despite small sample size, our study demonstrates that alloSCT has become a significantly safer procedure in patients with CLL.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701035","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}

{"title":"Targeting a CDH1–TK1–dependent DNA Synthesis Pathway Overcomes Chemoresistance in Acute Myeloid Leukemia","authors":"Xiaomin Feng,&nbsp;Li Huo,&nbsp;Clifford Pang,&nbsp;Zhihang Jiang,&nbsp;Yujuan Xue,&nbsp;Huimin Zeng","doi":"10.1002/hon.70238","DOIUrl":"10.1002/hon.70238","url":null,"abstract":"<div>\u0000 \u0000 <p>Relapsed and refractory acute myeloid leukemia (AML) remains difficult to treat, in part because leukemic cells adapt to nucleoside analogue-induced replication stress. Here, we identify thymidine kinase 1 (TK1) as a functional contributor to chemotherapy resistance in AML. Integrated analyses of TCGA, Beat AML, and murine chemoresistant AML transcriptomes revealed that high TK1 expression was associated with adverse outcome, cytarabine resistance, and enrichment of nucleotide salvage programs. In <i>Mll-Af9/Setd2</i>-mutant AML cells, TK1 upregulation coincided with reduced de novo nucleotide synthesis, sustained BrdU incorporation, attenuated replication stress signaling, and resistance to daunorubicin plus cytarabine. Genetic suppression of <i>Tk1</i> impaired DNA synthesis, increased replication-associated DNA damage, and restored chemosensitivity. Mechanistically, TK1 accumulation was linked to impaired APC/C-CDH1 activity, and manipulation of <i>Cdh1</i> altered TK1 abundance, replication stress tolerance, and drug response. Combined topoisomerase I and WEE1 inhibition increased CDH1 expression, reduced TK1 abundance, enforced replication stress, and induced leukemic cell death. In relapsed/refractory AML patient-derived xenograft models, this combination reduced leukemic burden and prolonged survival, particularly in TK1-high AML. These findings define a CDH1-TK1-associated program that promotes salvage-dependent replication stress tolerance and nominate TK1 as a candidate biomarker for replication stress-targeted therapy.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697447","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}

{"title":"Studying Chronic Lymphocytic Leukemia Microenvironment in the Multi Omics Era","authors":"Bucci Antonella,&nbsp;Notarpietro Giulia,&nbsp;Apollonio Benedetta,&nbsp;Vegliante Maria Carmela,&nbsp;Pappagallo Susanna Anita,&nbsp;Mondelli Paolo,&nbsp;Scattone Anna,&nbsp;Donati Benedetta,&nbsp;Ponzoni Maurilio,&nbsp;Frenquelli Michela,&nbsp;Ghia Paolo,&nbsp;Minoia Carla","doi":"10.1002/hon.70232","DOIUrl":"10.1002/hon.70232","url":null,"abstract":"<div>\u0000 \u0000 <p>In recent years, chronic lymphocytic leukemia (CLL) has undergone a radical change in the therapeutic landscape, allowing for the complete omission of chemotherapy in favor of targeted drugs. This reflects the improved understanding of the pathogenesis and biology of the disease, including both the genetic landscape of the leukemic clones and the crucial role of the numerous connections with the tumor microenvironment (TME). Regarding the latter, both in the bone marrow and in the lymph nodes, tissue architecture and function are reshaped by the lymphoid infiltrate to co-opt surrounding bystander cells, thereby supporting leukemic cell proliferation and survival. In this review, we explore the peculiarities of the CLL TME and how they translate into remarkable changes in the lymph nodal structure and in the inter-cellular interactions. We will elaborate on the potential that new multi-omics technologies might have in understanding the complex interplay occurring between CLL cells and TME.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684361","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}

{"title":"Defining a Therapeutic Window for Venetoclax in Post-Transplant Maintenance Therapy for High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndromes","authors":"Cuicui Lyu,&nbsp;Tianle Xie,&nbsp;Yedi Pu,&nbsp;Xianshuang Luan,&nbsp;Xia Xiao,&nbsp;Mingfeng Zhao,&nbsp;Hairong Lyu","doi":"10.1002/hon.70237","DOIUrl":"10.1002/hon.70237","url":null,"abstract":"<p>Patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) continue to face a substantial risk of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which remains a leading cause of treatment failure. In our previous study, maintenance therapy with a combination of venetoclax and decitabine has shown potential in reducing relapse rates; however, its efficacy and safety, particularly in relation to drug concentration levels, are not yet fully elucidated. This study aimed to evaluate the influence of venetoclax blood concentrations on the efficacy and toxicity of venetoclax plus decitabine as maintenance therapy in high-risk AML/MDS patients after allo-HSCT. We retrospectively analyzed clinical data from 58 high-risk AML/MDS patients who received this maintenance regimen at our center between April 2018 and June 2023, with a focus on the association between venetoclax blood levels, treatment response, and adverse effects. The results demonstrated that the venetoclax–decitabine maintenance regimen was effective and generally well-tolerated, improving remission rates without significantly increasing intolerable toxicities or the risk of graft-versus-host disease (GVHD). Notably, substantial interindividual variability in venetoclax blood concentrations was observed. Patients with concentrations maintained within the range of 2605–4060 ng/mL achieved superior outcomes and higher safety profiles. In conclusion, this study provides key evidence for establishing a target concentration window for venetoclax, highlighting the importance of therapeutic drug monitoring in guiding post-transplant maintenance therapy for high-risk AML/MDS patients.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"44 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}