Haematologica最新文献

{"title":"Characterization, outcome and identification of prognostic factors for patients with systemic immunoglobulin light-chain amyloidosis requiring dialysis prior to initial anti-clonal therapy.","authors":"Lilli S Sester,Paolo Milani,Fenia Theodorakakou,Tobias Dittrich,Jörg Beimler,Fabian Aus dem Siepen,Martin Zeier,Marc-Steffen Raab,Carsten Müller-Tidow,Efstathios Kastritis,Giovanni Palladini,Ute Hegenbart,Stefan O Schönland","doi":"10.3324/haematol.2025.287434","DOIUrl":"https://doi.org/10.3324/haematol.2025.287434","url":null,"abstract":"AL amyloidosis is a serious disease characterized by the deposition of immunoglobulin light chains in multiple organs. Renal involvement occurs in up to 70% of patients, but only a minority require dialysis before initiating anti-clonal treatment. Understanding the occurrence of end-stage organ damage is crucial to pave the way for reversing deposition. Currently, there is no detailed analysis available for this rare patient subgroup. We conducted a systematic search across three amyloidosis centers and characterized 68 biopsy-proven AL amyloidosis patients who required dialysis prior to initial anti-clonal therapy. In our cohort the second most affected organ was the heart. Renal parameters exhibited variability. Residual urine output and proteinuria ranged widely, while anuria had developed in only a few patients. Among the treated patients, 84% received Bortezomib as first-line therapy. The median overall survival (OS) was 44.8 months, with a median event-free survival (EFS) of 16.8 months. Our univariate statistical analysis revealed that underlying clonal disease, indicated by plasma cell infiltration, but not dFLC, impacted OS. Importantly, higher levels of troponins were associated with worse OS, confirmed by multivariate analysis, whereas NTproBNP levels and classical echocardiographic parameters such as septal thickness and longitudinal strain did not demonstrate significant prognostic value. This study provides crucial insights into this unique cohort of dialysis-dependent AL amyloidosis patients. The underlying clonal disease and markers of cardiac damage are important prognostic criteria. These findings emphasize the need to refine prognostic scoring systems for dialysis-dependent AL amyloidosis patients to better stratify risk and optimize treatment approaches.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"12 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optical genome mapping reveals complex cytogenetic abnormalities in multiple myeloma.","authors":"Jorge A Palacios,Mónica Bernal,Jose R Vílchez,Pilar Garrido,Pilar Jiménez,Juan F Gutiérrez-Bautista,María C Barrera-Aguilera,Lucía Ballesta,Teresa Rodríguez,María J Olivares-Durán,Francisco Ruiz-Cabello","doi":"10.3324/haematol.2025.288008","DOIUrl":"https://doi.org/10.3324/haematol.2025.288008","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"40 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extramedullary disease is associated with severe toxicities following B-cell maturation antigen CAR T-cell therapy in multiple myeloma.","authors":"Andrew J Portuguese,Emily C Liang,Jennifer J Huang,Yein Jeon,Danai Dima,Rahul Banerjee,Mary Kwok,Kara I Cicero,Alexandre V Hirayama,Ryan Basom,Christy Khouderchah,Mazyar Shadman,Lawrence Fong,Andrew J Cowan,Jordan Gauthier","doi":"10.3324/haematol.2025.287985","DOIUrl":"https://doi.org/10.3324/haematol.2025.287985","url":null,"abstract":"Extramedullary disease (EMD) in multiple myeloma (MM) is associated with poor outcomes following B-cell maturation antigen (BCMA)-targeted CAR-T therapy, yet its impact on treatment-related toxicity remains unclear. This study evaluates the impact of active EMD on toxicity, efficacy, and survival in patients with MM treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel). We conducted a retrospective cohort study of all patients with MM who received ide-cel (n=32) or cilta-cel (n=76) as standard-of-care therapy at our institution from August 2021 to October 2024. EMD was defined as the presence of soft tissue masses in extraosseous locations, and outcomes were compared based on EMD status. Among 108 patients, 26 (24%) had EMD. Patients with EMD experienced higher rates of grade (G)1+ (38% vs. 17%, p=0.022) and G3+ ICANS (19% vs. 1.2%, p=0.003), as well as G1+ (96% vs. 78%, p=0.041) and G3+ eICAHT (31% vs. 0%, p.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"15 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intensified conditioning with high-dose total marrow irradiation and myeloablative chemotherapy reduces risk of relapse without increasing toxicity in allogeneic hematopoietic stem cell transplant for high-risk myeloid malignancies: a phase II study.","authors":"Lucas Maahs,Ana Maria Avila,Matthew Koshy,Karen Sweiss,Kang-Hyun Ahn,Zhengjia Chen,Chukwuemeka Uzoka,Carlos Galvez,Matias Sanchez,Paul Rubinstein,John Quigley,Elisa Zucchetti,Nadim Mahmud,Bulent Aydogan,Pritesh Patel,Damiano Rondelli","doi":"10.3324/haematol.2025.287457","DOIUrl":"https://doi.org/10.3324/haematol.2025.287457","url":null,"abstract":"The intensity of the conditioning regimen in hematopoietic stem cell transplantation (HSCT) correlates with the risk of relapse, however its potential benefit may be outweighed by the associated risk of toxicity. The addition of total marrow irradiation (TMI) to myeloablative conditioning provides an opportunity to increase intensity with minimal additional toxicity. In this phase 2 clinical trial, 30 patients with high-risk myeloid malignancies received an allogeneic HSCT using myeloablative TMI at 9Gy in combination with standard myeloablative fludarabine/intravenous busulfan (FluBu4) chemotherapy. The study included patients with matched-related donors (n=10) receiving TMI/FluBu4 and patients with matched unrelated (n=14) or 1-antigen mismatched unrelated (n=6) donors receiving TMI/FluBu4 and rabbit antithymocyte globulin. All patients achieved sustained engraftment. Grade 3-4 extramedullary toxicities were: mucositis in 59% (n=17), nausea/vomiting in 10% (n=3) and diarrhea in 7% (n=2) of the patients. Acute graft-versus-host disease (GVHD) grade III-IV was seen in 4 patients (13.3%). Moderate/severe chronic GVHD was observed in 11 patients (36.7%). With a median follow-up of 1483 days (range: 63-2260 days) for patients alive, the overall survival and disease-free survival at 1 year were 72.4% and 65.5%, respectively. GVHD-Free Relapse-Free Survival at 1-year was 41.4%. Of 30 patients in the study, 6 relapsed/progressed (20%) and 5 of them died of the disease (16.7%); whereas 6 patients (20%) died of transplant-related mortality. We conclude that a myeloablative regimen with TMI at 9Gy and FluBu4 was well tolerated and achieved encouraging results in patients with myeloid malignancies at high risk of relapse (clinicaltrials.gov Identifier: NCT03121014).","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"51 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated 5-HTR7 deteriorates dysregulated megakaryocytopoiesis in immune thrombocytopenic purpura via up-regulating the PKA/Orai1/ERK1/2 pathway.","authors":"Meng Zhou,Haohao Han,Jiaqian Qi,Ziyan Zhang,Xiaofei Song,Xueqian Li,Tiantian Chu,Depei Wu,Yue Han","doi":"10.3324/haematol.2024.287287","DOIUrl":"https://doi.org/10.3324/haematol.2024.287287","url":null,"abstract":"Dysregulated megakaryocytopoiesis contributes to reduced platelet counts in immune thrombocytopenic purpura (ITP), yet the mechanism remains elusive. Although 5-hydroxytryptamine receptor 7 (5-HTR7) has been implicated in megakaryocyte (MK) biology, its pathogenic involvement in ITP is undefined. This study investigated the impact of 5-HTR7 on MK maturation in ITP using flow cytometry, immunofluorescence, and single-cell RNA sequencing (scRNA-seq). Analyses revealed elevated 5-HTR7 expression on MKs from ITP patients compared to healthy controls. Pharmacological inhibition of 5-HTR7 using SB269970A not only rescued MK maturation defects in vitro but also restored circulating platelet levels in a mouse model of active ITP. scRNA-seq coupled with western blot validation identified ERK1/2 phosphorylation in SB269970A-treated MKs. Mechanistically, 5-HTR7 impaired MK maturation through the PKA/Orai1/ERK axis by suppressing store-operated calcium entry (SOCE), as confirmed via confocal microscopy. In conclusion, elevated expression of 5-HTR7 impairs maturation of MKs causing lower platelet count in ITP, offering a potential therapeutic target for ITP management.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"5 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel PI3kδ inhibitor roginolisib synergizes with venetoclax in hematologic malignancies.","authors":"Binu Kandathilparambil Sasi,Chiara Tarantelli,Stephen Martindale,Elisa Civanelli,Eleonora Cannas,Giulio Sartori,Alberto J Arribas,Stacey M Fernandes,Samantha J Shupe,John-Hanson Machado,Svitlana Tyekucheva,Yue Ren,Michael Lahn,Lars Van der Veen,Giusy Di Conza,Francesco Bertoni,Jennifer R Brown","doi":"10.3324/haematol.2024.287180","DOIUrl":"https://doi.org/10.3324/haematol.2024.287180","url":null,"abstract":"The phosphoinositide 3-kinase (PI3K) pathway remains a potent drug target in hematological malignancies despite the challenges that have affected clinical drug development, particularly unpredictable toxicity, and inherent/acquired drug resistance. Herein, we tested the activity of a novel PI3Kδ selective, non-ATP competitive inhibitor, roginolisib (IOA-244), in hematological malignancies including diffuse large B cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL). To identify rational actionable combination partners that can be tested in hematologic malignancies, an unbiased pharmacological screening of 474 compounds was carried out in two lymphoma cell lines. We identified BCL2 blockade with venetoclax as synergistically active with roginolisib, a finding confirmed in a broad panel of lymphoma cell lines, DLBCL cell lines and primary CLL samples. We further demonstrate that the sensitizing effects of roginolisib to venetoclax correlate with suppression of downstream PI3K/AKT pathways and alterations in the expression of the apoptotic proteins BIM, mediated through FOXO1 transactivation, and MCL1, with ubiquitination and degradation mediated through GSK3α/β activation. These findings support proof of concept for roginolisib development in hematological malignancies as a single agent or in combination with venetoclax. A clinical trial of roginolisib with venetoclax and an anti-CD20 antibody is initiating in CLL.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"13 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurable residual disease recurrence as early warning of relapse in acute myeloid leukemia.","authors":"Benfa Gong, Miao Yang, Shaowei Qiu, Bingcheng Liu, Ying Wang, Yingchang Mi, Hui Wei, Jianxiang Wang","doi":"10.3324/haematol.2024.287119","DOIUrl":"https://doi.org/10.3324/haematol.2024.287119","url":null,"abstract":"<p><p>To investigate the clinical features and outcomes of measurable residual disease recurrence (MRD-R) by multiparameter flow cytometric in acute myeloid leukemia (AML). We retrospectively analyzed clinical characteristic, residual disease status and outcomes of 767 newly diagnosed AML patients achieving complete remission within two cycles of induction at our center. Totally, 171 (22.3%) patients experienced MRD-R during follow-up. Patients with MRD-R had inferior outcomes compared to those without MRD-R, with 3-year cumulative incidence of morphologic relapse (CIR), relapse-free survival (RFS) and overall survival (OS) at 63.6% vs. 30.6% (P.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"0"},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence-based quantitative bone marrow pathology analysis for myeloproliferative neoplasms.","authors":"Dandan Yu, Hongju Zhang, Yanyan Song, Yuan Tao, Fengyuan Zhou, Ziyi Wang, Rongfeng Fu, Ting Sun, Huan Dong, Wenjing Gu, Renchi Yang, Zhijian Xiao, Qi Sun, Lei Zhang","doi":"10.3324/haematol.2024.286123","DOIUrl":"https://doi.org/10.3324/haematol.2024.286123","url":null,"abstract":"<p><p>The evaluation of bone marrow pathology is essential for diagnosing and classifying myeloproliferative neoplasms (MPNs). However, morphological assessments of bone marrow trephine (BMT) sections by hematopathologists are inherently subjective; thus, an accurate and objective diagnostic system is needed. Based on U2-Net, UNeXt, and ResNet, we developed an automatic quantitative analysis platform of BMT sections from MPNs patients and nonneoplastic cases (n=342 total) to enhance the accuracy of diagnosis and classification of MPNs. Bone marrow metrics, including marrow cellularity, the myeloid-to-erythroid (M: E) ratio, megakaryocyte morphology and distribution, and the grading of marrow fibrosis (MF), were quantitatively analyzed (with an accuracy of approximately 0.9) based on the accuracy segmentation and identification of various cells and tissues (with an intersection over union (IoU) of roughly 0.8). A bone marrow classification model incorporating bone marrow metrics, a clinical classification model utilizing clinical features, and a comprehensive classification model that includes both bone marrow metrics and clinical features were developed using random forest classifiers to differentiate MPN subtypes and nonneoplastic conditions. The bone marrow and comprehensive classification models reached a macro-average area under the curve (AUC) of 0.96 for differentiating MPN subtypes and nonneoplastic cases. The clinical classification model attained a macro-average AUC of 0.92. This platform is highly accurate for quantitatively analyzing bone marrow pathology and classifying MPN subtypes and nonneoplastic cases. It can be a potentially auxiliary diagnostic tool for hematopathologists when dealing with patients with suspected MPNs.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"0"},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cilta-cel CAR T cells as an effective and well tolerated treatment for POEMS: a case study.","authors":"Matthew Williams, Djordje Atanackovic, Rediet Mulatu, Aerielle Matsangos, Daniel Yamoah, Ashraf Badros","doi":"10.3324/haematol.2025.287702","DOIUrl":"https://doi.org/10.3324/haematol.2025.287702","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-in-human pharmacokinetic, safety, and preliminary efficacy of single- and multiple-dose FRSW117, a novel PEGylated recombinant factor VIII-Fc fusion protein with an extended half-life, in patients with severe hemophilia A.","authors":"Feng Xue, Shuxia Guo, Ping Liu, Weizhi Chen, Yun Chen, Qing Wen, Haiying Hua, Yu Cao, Xianqi Feng, Jing Sun, Chongyuan Xu, Renchi Yang","doi":"10.3324/haematol.2024.286964","DOIUrl":"https://doi.org/10.3324/haematol.2024.286964","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}