Annals of Hematology最新文献

{"title":"Integrating genomic and transcriptome features for characterization and prognostic prediction of angioimmunoblastic T-cell lymphoma.","authors":"Chong Wei, Congwei Jia, Yan Zhang, Danqing Zhao, Wei Zhang, Daobin Zhou","doi":"10.1007/s00277-025-06589-3","DOIUrl":"https://doi.org/10.1007/s00277-025-06589-3","url":null,"abstract":"<p><p>In this study, we conducted integrated molecular analyses of the transcriptome and tumor genome in 24 newly diagnosed patients with angioimmunoblastic T-cell lymphoma (AITL). Gene expression profiling revealed significant enrichment of B cell receptor signaling and innate immune-related pathways in the response group. CIBERSORT-based deconvolution analysis showed that the proportions of tumor-infiltrating B cells and M1 macrophages were significantly higher in the response group compared to the non-response group (B cells: 17.4% vs. 7.8%, P = 0.012; M1 macrophages: 11.3% vs. 6.1%, P = 0.005). The abundance of these immune cells was associated with favorable progression-free survival and overall survival. Conversely, T follicular helper (TFH) cells, which reflect tumor burden, were inversely correlated with these favorable immune subsets. The most frequently mutated genes in this cohort included TET2 (73.9%), RHOA (47.8%), IDH2 (34.7%), and DNMT3A (26.1%). Mutations in RHOA, IDH2, and DNMT3A were negatively correlated with tumor-infiltrating B cells and were associated with poorer survival outcomes. Furthermore, higher variant allele frequencies (VAFs) of TET2 mutations were also negatively correlated with B cell infiltration, while RHOA VAFs were positively associated with TFH cell abundance, suggesting a link between mutational clonality and immune suppression. In conclusion, our study highlights the interplay between tumor genetic alterations and the immune microenvironment in AITL. We identified a favorable immune profile, characterized by increased infiltration of B cells and M1 macrophages, that correlates with chemosensitivity and improved prognosis. In contrast, mutations in RHOA, IDH2, DNMT3A, and high VAFs of TET2 were associated with adverse clinical outcomes and unfavorable immune contexture.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic factors and effect modifiers in patients with relapsed or refractory follicular lymphoma who failed at least two lines of therapy: a systematic literature and expert clinical review.","authors":"Pau Abrisqueta, Ana Jiménez-Ubieto, Ángel Serna, Irene Zamanillo, Yuting Kuang, Jennifer Uyei, Mohsin Shah, Laura Walsh, Eileen Thorley, Krystal Cantos, Emaan Rashidi, Qiufei Ma, Jessica J Jalbert, Alexi N Archambault, Yingxin Xu, Shivani Aggarwal, Srikanth Ambati, Hesham Mohamed, Christian Hampp, Bastian von Tresckow","doi":"10.1007/s00277-025-06575-9","DOIUrl":"https://doi.org/10.1007/s00277-025-06575-9","url":null,"abstract":"<p><p>To enhance the quality of real-world external comparative studies, it is essential to systematically identify, prespecify, and account for prognostic variables and effect measure modifiers (EMMs), especially between emulated target trial and real-world control arms. These factors can then be utilized to evaluate cohort comparability and perform covariate adjustments, such as in propensity score models. A systematic literature review (SLR)-based identification of prognostic factors, coupled with expert clinical review, offers a comprehensive approach to evaluating and ranking the level of evidence, while also assisting in selection of prognostic factors to assess imbalances between cohorts in single-arm trials and real-world data studies. We performed an SLR followed by a clinical review and ranking by subject-matter experts to identify prognostic factors and EMMs in patients with relapsed or refractory (r/r) follicular lymphoma (FL) who failed at least two lines of therapy (LoTs). Across 13 included studies, the SLR identified 28 prognostic factors that were significantly associated with clinical outcomes, including overall survival, progression-free survival, and objective response rate. Notably, our review did not identify any statistically significant EMMs. Based on expert ranking of the SLR-derived list, the 5 most important prognostic variables in descending order are: progression of disease within 24 months of first LoT (POD24), chemo-immunorefractory/chemoresistant, refractory to last LoT, number of prior LoTs, and serum lactate dehydrogenase. This comprehensive SLR and expert review highlight critical prognostic factors in r/r FL. The identified prognostic variables can inform future research, emphasizing the need for continued investigation into factors affecting outcomes in this challenging and heterogeneous patient population.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the akt/mtor signaling pathway by maprotiline leads to tumor suppression in T-cell lymphoma.","authors":"Xiaodong Li, Jie Chen, Riyi Zhang, Songyan Zou, Dongdong Yang, Wei Tu, Fuyi Xie, Yinyu Mu","doi":"10.1007/s00277-025-06571-z","DOIUrl":"https://doi.org/10.1007/s00277-025-06571-z","url":null,"abstract":"<p><p>T-cell lymphoma (TCL) is a prevalent malignancy characterized by the aberrant proliferation of T cells. The molecular mechanism underlying TCL remains poorly understood, and effective therapeutic strategies are still limited. Maprotiline, a highly selective norepinephrine reuptake blocker, is primarily used in the treatment of various types of depression. Intriguingly, its potential therapeutic utility and underlying mechanisms in TCL have not been previously explored. In this study, we demonstrated for the first time that maprotiline significantly inhibits proliferation and migration while promoting apoptosis in TCL cells. Furthermore, in vivo experiments using TCL xenograft mouse models revealed that maprotiline treatment effectively suppresses tumor progression while maintaining a favorable safety profile with minimal toxicity. Mechanistically, our findings reveal that maprotiline exerts its anti-tumor effect by regulating the AKT/mTOR signaling pathway in TCL. Notably, we discovered that maprotiline substantially enhances the sensitivity of TCL cells to histone deacetylase inhibitor, thereby unveiling a promising combination therapeutic strategy for TCL treatment. These findings not only expand our understanding of maprotiline's pharmacological potential beyond its conventional antidepressant use, but also provide a novel therapeutic avenue for addressing the clinical challenges in TCL management.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapidly progressing after umbilical cord blood transplantation in a boy with acute myeloid leukemia with KAT6A::EP300 fusion transcript.","authors":"Yongren Wang, Wei Zong, Jingjing Fan, LiuCheng Rong, Yongjun Fang","doi":"10.1007/s00277-025-06573-x","DOIUrl":"https://doi.org/10.1007/s00277-025-06573-x","url":null,"abstract":"","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Follicular lymphoma or diffuse large B-cell lymphoma: a population based analysis of epidemiological and health economic aspects in Germany.","authors":"Karin Berger, Bernhard Moertl, Michael von Bergwelt-Baildon, Dominik Obermüller, Dorota Pawlowska-Phelan, Martin Dreyling","doi":"10.1007/s00277-025-06592-8","DOIUrl":"https://doi.org/10.1007/s00277-025-06592-8","url":null,"abstract":"<p><p>Contemporary information on epidemiology, healthcare resource utilization (HCRU), costs and clinical outcomes in routine care is essential for value-based decision-making. However, such information remains limited for follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) in Germany. This study addresses these gaps. This retrospective cross-sectional cost-of-illness study analyzed anonymized statutory health insurance claims data (2015-2020). FL Grade I-IIIa (ICD-10: C82.0-C82.3), DLBCL (ICD-10: C83.3) patients were identified via inpatient or outpatient ICD coding. Elixhauser and Charlson Comorbidity Indices were used to describe the general comorbidity burden. FL prevalence increased from 26 to 32 per 100,000 insured persons (n = 837 to 1,028), DLBCL prevalence rose from 37 to 45 per 100,000 (n = 1,205 to 1,437). Mean age (FL: 67.0 ± 13; DLBCL: 68.6 ± 13.6) and sex distribution (FL: 50% female; DLBCL: 44% female) remained stable 2015-2020. Mean Charlson Comorbidity Index 4.1 ± 2.4 (FL), 4.8 ± 2.7 (DLBCL), mean Elixhauser 5.2 ± 3.0 (FL), 6.1 ± 3.3 (DLBCL). Hospitalization rates: 64% of FL patients (2.0 ± 2.3 admissions, 21 ± 44.7 days/year); 78% of DLBCL patients (2.9 ± 3.1 admissions, 29 ± 47.5 days/year). Mean annual costs per patient in third-party payers perspective were €15,258 (FL), €23,455 (DLBCL). Post-SCT 12-month costs were €46,270 (FL), €56,558 (DLBCL) for autologous-SCT, and €161,662 for allogeneic-SCT (DLBCL only). Rising prevalence calls for ongoing real-world assessment of HCRU and costs. This study supplements limited evidence, highlighting significant economic impact. While health insurance data offer valuable insights, their lack of clinical details necessitates integration with other data sources. Several initiatives are building data spaces to enhance evidence generation; meanwhile, analyses based on single data sources remain valuable to inform practice and policy.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analytical considerations affecting plasma free haemoglobin, the haemolysis index, and correlation with clinical outcomes in sickle cell disease.","authors":"Guillaume Feugray, Julie Fettig, Valéry Brunel","doi":"10.1007/s00277-025-06534-4","DOIUrl":"https://doi.org/10.1007/s00277-025-06534-4","url":null,"abstract":"","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of laboratory biomarkers for mortality risk stratification in thrombotic thrombocytopenic purpura.","authors":"Xu Xiang, Yue-Qing Dai","doi":"10.1007/s00277-025-06584-8","DOIUrl":"https://doi.org/10.1007/s00277-025-06584-8","url":null,"abstract":"<p><p>This study aimed to explore the relationship between laboratory indicators and short-term mortality risk in patients with thrombotic thrombocytopenic purpura (TTP) and to construct a risk stratification model. We retrospectively analyzed the clinical data of 106 patients with TTP admitted to Tongji Hospital between June 2016 and February 2025. Patients were grouped by 28-day survival: death (n = 45) and survival (n = 61). Prognosis-related indicators were identified using receiver operating characteristic (ROC) curves and logistic regression analyses. A mortality risk stratification model was established. To validate the stability of the model, 30 external cases of TTP (January 2022-December 2024) were collected. The levels of cardiac troponin I (cTnI), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and indirect bilirubin (IBIL) were significantly higher in the death group compared to those in the survival group. ROC analysis identified optimal mortality risk cutoffs: cTnI at 353.1 pg/mL (odds ratio [OR] = 4.778), LDH at 992 U/L (OR = 2.842), BUN at 10.9 mmol/L (OR = 5.527), and IBIL at 32.3 µmol/L (OR = 2.995). A subsequent 0-4 point risk stratification model demonstrated increasing mortality rates of 21.3% (0-1 point), 39.1% (2 points), 60.9% (3 points), and 92.3% (4 points). Each 1-point increase in the risk score was associated with a 2.324-fold rise in mortality risk (95% confidence interval 1.597-3.383). Internal and external validations confirmed the model's stability and strong prognostic performance in patients with TTP. The risk model incorporating cTnI, LDH, BUN, and IBIL levels effectively predicted short-term mortality in patients with TTP. Patients with a score of 3 or higher required close monitoring and aggressive therapeutic intervention to mitigate mortality risk.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful repeated endoscopic balloon dilatation for esophageal stricture as chronic graft-versus-host disease.","authors":"Erika Sekiguchi, Masatoshi Sakurai, Takahiro Inoue, Kyoko Masuda, Yusuke Kubota, Takahide Shindo, Tomohiko Tanigawa, Akihiko Chida, Jun Kato, Hirofumi Kawakubo, Keisuke Kataoka","doi":"10.1007/s00277-025-06590-w","DOIUrl":"https://doi.org/10.1007/s00277-025-06590-w","url":null,"abstract":"","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clinical features and outcomes of aggressive large B cell lymphoma with concomitant hemophagocytic lymphohistiocytosis at diagnosis.","authors":"Lixia Zhu, Mengqi Xiong, Zixi Wang, Li Li, Jingsong He, Lijun Wang, He Huang, Xiujin Ye","doi":"10.1007/s00277-025-06574-w","DOIUrl":"https://doi.org/10.1007/s00277-025-06574-w","url":null,"abstract":"<p><p>Hemophagocytic lymphohistiocytosis (HLH), as a life-threatening hyperinflammatory syndrome, rarely presents as a harbinger of aggressive large B cell lymphoma (LBCL), with a rapidly progressive clinical course and poor prognosis. A total of 30 patients diagnosed with aggressive LBCL concurrent with HLH were retrospectively reviewed in this study. Median age was 60 years (range, 24 to 85 years). Thirteen (43.3%) patients treated with ruxolitinib combined with corticosteroid (Ru-D) regimen achieved the highest overall response rate (ORR) of 84.6%, which was significantly higher than that of 40.0% in the etoposide and corticosteroid group and 33.3% in the corticosteroid group (P = 0.019). The median overall survival (OS) was 16.2 months, with corresponding 1-year and 2-year OS rates of 63.3% and 38.4%, respectively. The 8-week mortality rate was 26.7%. Patients responded to anti-HLH therapy within 2 weeks had significantly better OS than non-responsive group (P = 0.009). Low-intensity chemotherapy without anthracycline as the first-line of anti-lymphoma therapy followed by RCHOP did not compromise survival, and the median OS was 13 months and 19.1 months, respectively (P = 0.457). Ferritin levels ≥ 3606 ng/mL and uncontrolled HLH within 2 weeks were the independent risk factors associated with inferior OS. Our findings highlight the high early mortality and short survival of these patients and underscore the urgent need for developing more effective treatment strategies to improve prognosis.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 with prior pembrolizumab and bendamustine therapy induce complete metabolic response in relapsed/refractory classical hodgkin lymphoma with relapse after nivolumab.","authors":"Ugo Giordano, Agnieszka Kuś, Karolina Kędziora, Mateusz Sawicki, Zbigniew Podgajny, Monika Mordak-Domagała, Zuzanna Dybko, Jarosław Dybko","doi":"10.1007/s00277-025-06568-8","DOIUrl":"https://doi.org/10.1007/s00277-025-06568-8","url":null,"abstract":"<p><p>Relapsed/refractory classical Hodgkin lymphoma (r/r cHL) poses a therapeutic challenge, particularly after failure of checkpoint inhibitors (CPIs) and brentuximab vedotin. We report a case of a heavily pretreated young male patient with r/r cHL who achieved complete metabolic response (CMR) after allogeneic hematopoietic stem cell transplantation (allo-HCT) following pembrolizumab and bendamustine therapy, currently in CMR at 19 months post-transplantation. Despite prior resistance to nivolumab, pembrolizumab combined with bendamustine contributed to disease control in the pre-transplant period. This case highlights allo-HCT's curative potential even in partial responders and suggests that pre-transplant CPI therapy may enhance the graft-versus-lymphoma effect, improving post-transplantation outcomes in r/r cHL. Another explanation for the therapeutic success may be that the employment of a CPI has likely contributed to sensitization to chemotherapy and bendamustine potentially lowering the occurrence of GvHD due to T-cell compartment impairment, with the need for large scale prospective trials to demonstrate our findings.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}