Blood Cancer Journal最新文献

{"title":"Treatment with obinutuzumab plus venetoclax reshapes the TRB repertoire of CLL patients","authors":"Paul J. Hengeveld, Joyce Schilperoord-Vermeulen, P. Martijn Kolijn, Julie M. N. Dubois, Peter E. Westerweel, Sabina Kersting, Arnon P. Kater, Mark-David Levin, Anton W. Langerak","doi":"10.1038/s41408-025-01209-9","DOIUrl":"https://doi.org/10.1038/s41408-025-01209-9","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"27 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934500","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":"Updated analysis of EMN02 demonstrated overall survival benefit to early ASCT for multiple myeloma.","authors":"Alfred L Garfall","doi":"10.1038/s41408-024-01198-1","DOIUrl":"10.1038/s41408-024-01198-1","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"15 1","pages":"1"},"PeriodicalIF":12.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of clinical outcomes and molecular features in extramedullary disease in multiple myeloma","authors":"Rie Nakamoto-Matsubara, Valentina Nardi, Nora Horick, Tsuyoshi Fukushima, Ryan S. Han, Rajib Shome, Kiyosumi Ochi, Cristina Panaroni, Keertik Fulzele, Farah Rexha, Andrew R. Branagan, Diana Cirstea, Andrew J. Yee, David T. Scadden, Noopur S. Raje","doi":"10.1038/s41408-024-01190-9","DOIUrl":"https://doi.org/10.1038/s41408-024-01190-9","url":null,"abstract":"<p>Multiple myeloma (MM) remains incurable despite novel therapeutics. A major contributor to the development of relapsed/refractory and resistant MM is extraosseous extramedullary disease (EMD), whose molecular biology is still not fully understood. We analyzed 528 MM patients who presented to our institution between 2014 and 2021 and who had undergone molecular testing. We defined EMD as organ plasmacytoma distinct from bones and evaluated patients for the development of EMD with the goal of defining their molecular characteristics. Here, we show that <i>RAS/BRAF</i> mutations are likely essential for the development of EMD. Our results also indicate that the underlying reason for the negative outcomes in patients with poor prognostic factors such as duplication 1q and deletion 17p is largely due to the development of EMD. However, the presence of <i>TP53</i> mutation remains a poor prognostic factor regardless of EMD development. Furthermore, mutation sites of <i>TP53</i> were different between EMD versus non-EMD patients, with gain-of-function mutations enriched in patients with EMD. Our data highlights distinct molecular abnormalities in patients with EMD and provides potential mechanistic insights for novel therapeutic targets for the future.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"280 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873942","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":"Global disparities in drug-related adverse events of patients with multiple myeloma: a pharmacovigilance study","authors":"Majid Jaberi-Douraki, Xuan Xu, Danai Dima, Sikander Ailawadhi, Faiz Anwer, Sandra Mazzoni, Jason Valent, Muhammad Hamza Habib, Jim E. Riviere, Shahzad Raza","doi":"10.1038/s41408-024-01206-4","DOIUrl":"https://doi.org/10.1038/s41408-024-01206-4","url":null,"abstract":"<p>Multiple myeloma (MM) is a complex hematological malignancy of clonal plasma cells driven by alterations to the chromosomal material leading to uncontrolled proliferation in the bone marrow. Ethnic and racial disparities persist in the prevalence, diagnosis, management, and outcomes of MM. These disparities are multifaceted and intersect with various factors, including demographics, geography, socioeconomic status, genetics, and access to healthcare. This study utilized the openFDA human drug adverse events (AEs) to analyze global data pertaining to MM patients and patterns of treatment-related AEs. We identified ten most frequently used drugs and drug regimens in six distinct regions, including North America (NA), Europe (EU), Asia (AS), Africa (AF), Oceania (OC), and Latin America &amp; the Caribbean (LA). AE patterns were evaluated using the reporting odds ratio combined with a 95% confidence interval. AE reports were more prevalent in men than in women across all regions. Cardiotoxicities were more likely observed in AS and EU, while secondary neoplasms were more frequently reported in the EU. Nephropathies were prominent in OC, AF (in males), and AS (in females), while vascular toxicity, including embolism and thrombosis, was more common in NA (in males). A notable improvement in survival, particularly in AS, EU, and NA, with a significant decline in death rates was observed. Hospitalization rates displayed less variation in AS and EU but exhibited more pronounced fluctuations in AF, LA, and OC. In conclusion, this comprehensive analysis offers valuable insights into the demographic, geographic, and AE patterns of MM patients across the globe.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"69 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858430","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":"Clinical characteristics and outcomes of 476 mantle cell lymphoma patients aged 80 years and older","authors":"Simon Pahnke, Kossi D. Abalo, Sara Ekberg, Alexandra Albertsson-Lindblad, Karin E. Smedby, Mats Jerkeman, Ingrid Glimelius","doi":"10.1038/s41408-024-01204-6","DOIUrl":"https://doi.org/10.1038/s41408-024-01204-6","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"8 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849150","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":"Expanded tumor-associated polymorphonuclear myeloid-derived suppressor cells in Waldenstrom macroglobulinemia display immune suppressive activity","authors":"Vaishali Bhardwaj, Zhi-Zhang Yang, Shahrzad Jalali, Jose C. Villasboas, Rekha Mudappathi, Junwen Wang, Prithviraj Mukherjee, Jonas Paludo, Xinyi Tang, Hyo Jin Kim, Jordan E. Krull, Kerstin Wenzl, Anne J. Novak, Patrizia Mondello, Stephen M. Ansell","doi":"10.1038/s41408-024-01173-w","DOIUrl":"https://doi.org/10.1038/s41408-024-01173-w","url":null,"abstract":"<p>The role of the bone marrow (BM) microenvironment in regulating the antitumor immune response in Waldenstrom macroglobulinemia (WM) remains poorly understood. Here we transcriptionally and phenotypically profiled non-malignant (CD19^- CD138^-) BM cells from WM patients with a focus on myeloid derived suppressive cells (MDSCs) to provide a deeper understanding of their role in WM. We found that HLA-DR^lowCD11b⁺CD33⁺ MDSCs were significantly increased in WM patients as compared to normal controls, with an expansion of predominantly polymorphonuclear (PMN)-MDSCs. Single-cell immunogenomic profiling of WM MDSCs identified an immune-suppressive gene signature with upregulated inflammatory pathways associated with interferon and tumor necrosis factor (TNF) signaling. Gene signatures associated with an inflammatory and immune suppressive environment were predominately expressed in PMN-MDSCs. In vitro, WM PMN-MDSCs demonstrated robust T-cell suppression and their viability and expansion was notably enhanced by granulocyte colony stimulating factor (G-CSF) and TNFα. Furthermore, BM malignant B-cells attracted PMN-MDSCs to a greater degree than monocytic MDSCs. Collectively, these data suggest that malignant WM B cells actively recruit PMN-MDSCs which promote an immunosuppressive BM microenvironment through a direct T cell inhibition, while release of G-CSF/TNFα in the microenvironment further promotes PMN-MDSC expansion and in turn immune suppression. Targeting PMN-MDSCs may therefore represent a potential therapeutic strategy in patients with WM.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"42 2 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841071","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":"The significance of free light-chain ratio in light-chain monoclonal gammopathy of undetermined significance: a flow cytometry sub-study of the iStopMM screening study","authors":"Jón Þórir Óskarsson, Sæmundur Rögnvaldsson, Sigrun Thorsteinsdottir, Thorir Einarsson Long, Andri Ólafsson, Elias Eythorsson, Ásbjörn Jónsson, Brynjar Viðarsson, Páll T. Önundarson, Bjarni A. Agnarsson, Róbert Pálmason, Margrét Sigurðardóttir, Ingunn Þorsteinsdóttir, Ísleifur Ólafsson, Stephen J. Harding, Brian G. M. Durie, Thorvardur Jon Love, Sigurdur Y. Kristinsson","doi":"10.1038/s41408-024-01201-9","DOIUrl":"https://doi.org/10.1038/s41408-024-01201-9","url":null,"abstract":"<p>Light-chain (LC) monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. LC-MGUS is characterized by free light-chain (FLC) levels outside defined reference intervals, indirectly indicating underlying plasma cell (PC) monoclonality. Next-generation flow cytometry (NGF) was used to evaluate clonal PC presence in bone marrow (BM) samples from individuals with LC-MGUS in the iStopMM study, aiming to assess the predictive value of the FLC ratio for clonal PC presence and its prognostic implications. BM samples from 61 individuals with LC monoclonal gammopathy were analyzed. Clonal plasma cells were detected in 53.6% of LC-MGUS samples (<i>n</i> = 28) and in all samples from individuals with more advanced conditions (<i>n</i> = 33). The FLC ratio was predictive of clonal PC presence for kappa-involved FLC ratios (<i>p</i> &lt; 0.05; <i>n</i> = 42), with an optimal cutoff of 3.15 (96.7% sensitivity, 91.7% specificity). Of 195 individuals with kappa-involved LC-MGUS in follow-up within the iStopMM study, none with FLC ratios &gt;1.65 to 3.15 progressed to MM (<i>n</i> = 124), whereas 4/71 (5.6%) with FLC ratios &gt;3.15 progressed over median follow-up of 55 months. These findings support using a kappa-involved FLC ratio cutoff of &gt;3.15 to more accurately identify individuals at increased risk of developing symptomatic PC disorders.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"77 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849152","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":"Evaluation of gecacitinib vs hydroxyurea in patients with intermediate-2 or high-risk myelofibrosis: final analysis results from a randomized phase 3 study","authors":"Yi Zhang, Hu Zhou, Shanshan Suo, Junling Zhuang, Linhua Yang, Aili He, Qingchi Liu, Xin Du, Sujun Gao, Yarong Li, Yan Li, Yuqing Chen, Wen Wu, Huanling Zhu, Guangsheng He, Mei Hong, Qian Jiang, Zhongxing Jiang, Hongmei Jing, Jishi Wang, Na Xu, Lingling Yue, Cuiping Zheng, Zeping Zhou, Chenghao Jin, Xin Li, Lin Liu, Yajing Xu, Dengshu Wu, Feng Zhang, Jin Zhang, Liqing Wu, Hewen Yin, Binhua Lv, Zhijian Xiao, Jie Jin","doi":"10.1038/s41408-024-01202-8","DOIUrl":"https://doi.org/10.1038/s41408-024-01202-8","url":null,"abstract":"<p>To compare the efficacy and safety of gecacitinib (also known as jaktinib) with hydroxyurea (HU) in treating myelofibrosis (MF) patients. In this multicenter, randomized phase 3 trial (ZGJAK016), intermediate- or high-risk primarily JAK inhibitor naïve MF patients were assigned in a 2:1 ratio to receive either gecacitinib (100 mg twice a day, BID) or HU (500 mg BID). The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) from baseline at week 24. Secondary endpoints included the best spleen response rate, the proportion of patients with a ≥50% reduction in total symptom score (TSS50), anemia improvement, and safety profile. At 24 weeks, the SVR35 was reached by 64.8% of patients on gecacitinib (46/71), compared to 26.5% on HU (9/34), <i>P</i> = 0.0002. The best spleen response rates were also superior for gecacitinib at 81.7%, vs 32.4% for HU, <i>P</i> &lt; 0.0001. The TSS50 rates were 62.0% for gecacitinib- and 50% for HU-treated patients. Among non-transfusion-dependent patients with baseline hemoglobin (HGB) ≤ 100 g/L, 31.0% (13/42) in the gecacitinib group showed a ≥20 g/L increase in HGB, compared to 15.0% (3/20) in HU group. The common grade ≥ 3 treatment-emergent adverse events (TEAEs), including anemia (26.8% vs 44.1%), thrombocytopenia (15.5% vs 32.4%), leukopenia (2.8% vs 20.6%), and neutropenia (1.4% vs 20.6%), were less frequent with gecacitinib than HU. Treatment discontinuation due to TEAEs was lower in gecacitinib (7.0%) compared to HU (11.8%). Gecacitinib demonstrates superior efficacy and a more favorable safety profile compared to HU, making it a promising treatment option for managing MF, particularly in patients with anemia (This trial was registered with ClinicalTrials.gov, (NCT04617028)).</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"13 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841024","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":"Elranatamab monotherapy in the real-word setting in relapsed-refractory multiple myeloma: results of the French compassionate use program on behalf of the IFM","authors":"Florent Malard, Arthur Bobin, Myriam Labopin, Lionel Karlin, Laurent Frenzel, Murielle Roussel, Marguerite Vignon, Sophie Godet, Thomas Chalopin, Perrine Moyer, Emilie Chalayer, Frederique Orsini Piocelle, Clara Mariette, Carolyne Croizier, Claudine Sohn, Mamoun Dib, Ronan Le Calloch, Nadia Ali-Ammar, Marion Loirat, Omar Benbrahim, Alexandre Payssot, Adrien Trebouet, Aurore Perrot, Xavier Leleu, Mohamad Mohty","doi":"10.1038/s41408-024-01200-w","DOIUrl":"https://doi.org/10.1038/s41408-024-01200-w","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"64 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841023","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":"Single-cell transcriptomic and spatial analysis reveal the immunosuppressive microenvironment in relapsed/refractory angioimmunoblastic T-cell lymphoma","authors":"Mengyan Zhu, Ning Li, Lei Fan, Rongrong Wu, Lei Cao, Yimin Ren, Chuanyang Lu, Lishen Zhang, Yun Cai, Yuzhu Shi, Zihan Lin, Xueying Lu, Jiayan Leng, Shiyang Zhong, Xingfei Hu, Bin Huang, Runheng Huang, Wanting Zhou, Diru Yao, Lingxiang Wu, Wei Wu, Quanzhong Liu, Peng Xia, Ruize Chen, Wenyu Shi, Ruohan Zhang, Sali Lv, Chunling Wang, Liang Yu, Jianyong Li, Qianghu Wang, Kening Li, Hui Jin","doi":"10.1038/s41408-024-01199-0","DOIUrl":"https://doi.org/10.1038/s41408-024-01199-0","url":null,"abstract":"<p>Angioimmunoblastic T-cell lymphoma (AITL) is a kind of aggressive T-cell lymphoma with significant enrichment of non-malignant tumor microenvironment (TME) cells. However, the complexity of TME in AITL progression is poorly understood. We performed single-cell RNA-Seq (scRNA-seq) and imaging mass cytometry (IMC) analysis to compare the cellular composition and spatial architecture between relapsed/refractory AITL (RR-AITL) and newly diagnosed AITL (ND-AITL). Our results showed that the malignant T follicular helper (Tfh) cells showed significantly increased proliferation driven by transcriptional activation of YY1 in RR-AITL, which is markedly associated with the poor prognosis of AITL patients. The CD8⁺ T cell proportion and cytotoxicity decreased in RR-AITL TME, resulting from elevated expression of the inhibitory checkpoints such as PD-1, TIGIT, and CTLA4. Notably, the transcriptional pattern of B cells in RR-AITL showed an intermediate state of malignant transformation to B-cell-lymphoma, and contributed to immune evasion by highly expressing CD47 and PD-L1. Besides, compared to ND-AITL samples, myeloid-cells-centered spatial communities were more prevalent but showed reduced phagocytic activity and impaired antigen processing and presentation in RR-AITL TME. Furthermore, specific inhibitory ligand-receptor interactions, such as <i>CLEC2D</i>-<i>KLRB1</i>, <i>CTLA4</i>-<i>CD86</i>, and <i>MIF</i>-<i>CD74</i>, were exclusively identified in the RR-AITL TME. Our study provides a high-resolution characterization of the immunosuppression ecosystem and reveals the potential therapeutic targets for RR-AITL patients.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"47 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841069","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}