Journal of Hematology & Oncology最新文献

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A single-cell transcriptomic map of the murine and human multiple myeloma immune microenvironment across disease stages 跨疾病阶段的小鼠和人类多发性骨髓瘤免疫微环境单细胞转录组图谱
IF 28.5 1区 医学
Journal of Hematology & Oncology Pub Date : 2024-11-07 DOI: 10.1186/s13045-024-01629-3
Emma Verheye, Daliya Kancheva, Hatice Satilmis, Niels Vandewalle, Rong Fan, Pauline M. R. Bardet, Emile J. Clappaert, Kevin Verstaen, Ann De Becker, Karin Vanderkerken, Kim De Veirman, Damya Laoui
{"title":"A single-cell transcriptomic map of the murine and human multiple myeloma immune microenvironment across disease stages","authors":"Emma Verheye, Daliya Kancheva, Hatice Satilmis, Niels Vandewalle, Rong Fan, Pauline M. R. Bardet, Emile J. Clappaert, Kevin Verstaen, Ann De Becker, Karin Vanderkerken, Kim De Veirman, Damya Laoui","doi":"10.1186/s13045-024-01629-3","DOIUrl":"https://doi.org/10.1186/s13045-024-01629-3","url":null,"abstract":"The long-term effectiveness of immunotherapies against Multiple Myeloma (MM) remains elusive, demonstrated by the inevitable relapse in patients. This underscores the urgent need for an in-depth analysis of the MM tumor-immune microenvironment (TME). Hereto, a representative immunocompetent MM mouse model can offer a valuable approach to study the dynamic changes within the MM-TME and to uncover potential resistance mechanisms hampering effective and durable therapeutic strategies in MM. We generated a comprehensive single-cell RNA-sequencing atlas of the MM-TME in bone marrow and spleen encompassing different stages of disease, using the immunocompetent 5T33MM mouse model. Through comparative analysis, we correlated our murine dataset with the pathogenesis in MM patients by reanalyzing publicly available datasets of human bone marrow samples across various disease stages. Using flow cytometry, we validated the dynamic changes upon disease progression in the 5T33MM model. Furthermore, interesting target populations, as well as the immune-boosting anti-CD40 agonist (αCD40) therapy were tested ex vivo on murine and human primary samples and in vivo using the 5T33MM model. In this study, we identified the heterogenous and dynamic changes within the TME of murine and human MM. We found that the MM-TME was characterized by an increase in T cells, accompanied with an exhausted phenotype. Although neutrophils appeared to be rather innocuous at early disease stages, they acquired a pro-tumorigenic phenotype during MM progression. Moreover, conventional dendritic cells (cDCs) showed a less activated phenotype in MM, underscoring the potential of immune-boosting therapies such as αCD40 therapy. Importantly, we provided the first pre-clinical evaluation of αCD40 therapy and demonstrated successful induction of cDC- and T-cell activation, accompanied by a significant short-term anti-tumor response. This resource provides a comprehensive and detailed immune atlas of the evolution in human and murine MM disease progression. Our findings can contribute to immune-based patient stratification and facilitate the development of novel and durable (immune) therapeutic strategies in MM.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"8 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596976","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}
引用次数: 0
Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms 嗜血细胞淋巴组织细胞增多症:当前的治疗进展、新兴靶向疗法和潜在机制
IF 28.5 1区 医学
Journal of Hematology & Oncology Pub Date : 2024-11-07 DOI: 10.1186/s13045-024-01621-x
Yijun Wu, Xu Sun, Kai Kang, Yuqi Yang, He Li, Ailin Zhao, Ting Niu
{"title":"Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms","authors":"Yijun Wu, Xu Sun, Kai Kang, Yuqi Yang, He Li, Ailin Zhao, Ting Niu","doi":"10.1186/s13045-024-01621-x","DOIUrl":"https://doi.org/10.1186/s13045-024-01621-x","url":null,"abstract":"Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressing, life-threatening syndrome characterized by excessive immune activation, often presenting as a complex cytokine storm. This hyperactive immune response can lead to multi-organ failure and systemic damage, resulting in an extremely short survival period if left untreated. Over the past decades, although HLH has garnered increasing attention from researchers, there have been few advancements in its treatment. The cytokine storm plays a crucial role in the treatment of HLH. Investigating the detailed mechanisms behind cytokine storms offers insights into targeted therapeutic approaches, potentially aiding in early intervention and improving the clinical outcome of HLH patients. To date, there is only one targeted therapy, emapalumab targeting interferon-γ, that has gained approval for primary HLH. This review aims to summarize the current treatment advances, emerging targeted therapeutics and underlying mechanisms of HLH, highlighting its newly discovered targets potentially involved in cytokine storms, which are expected to drive the development of novel treatments and offer fresh perspectives for future studies. Besides, multi-targeted combination therapy may be essential for disease control, but further trials are required to determine the optimal treatment mode for HLH.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"94 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594813","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}
引用次数: 0
Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies 优化治疗实体瘤的 CAR-T 细胞疗法:当前挑战与潜在策略
IF 28.5 1区 医学
Journal of Hematology & Oncology Pub Date : 2024-11-05 DOI: 10.1186/s13045-024-01625-7
Kexin Ai, Bowen Liu, Xiaomei Chen, Chuxin Huang, liping Yang, Weiya Zhang, Jianyu Weng, Xin Du, Kongming Wu, Peilong Lai
{"title":"Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies","authors":"Kexin Ai, Bowen Liu, Xiaomei Chen, Chuxin Huang, liping Yang, Weiya Zhang, Jianyu Weng, Xin Du, Kongming Wu, Peilong Lai","doi":"10.1186/s13045-024-01625-7","DOIUrl":"https://doi.org/10.1186/s13045-024-01625-7","url":null,"abstract":"Chimeric antigen receptor (CAR)-T cell therapy demonstrates substantial efficacy in various hematological malignancies. However, its application in solid tumors is still limited. Clinical studies report suboptimal outcomes such as reduced cytotoxicity of CAR-T cells and tumor evasion, underscoring the need to address the challenges of sliding cytotoxicity in CAR-T cells. Despite improvements from fourth and next-generation CAR-T cells, new challenges include systemic toxicity from continuously secreted proteins, low productivity, and elevated costs. Recent research targets genetic modifications to boost killing potential, metabolic interventions to hinder tumor progression, and diverse combination strategies to enhance CAR-T cell therapy. Efforts to reduce the duration and cost of CAR-T cell therapy include developing allogenic and in-vivo approaches, promising significant future advancements. Concurrently, innovative technologies and platforms enhance the potential of CAR-T cell therapy to overcome limitations in treating solid tumors. This review explores strategies to optimize CAR-T cell therapies for solid tumors, focusing on enhancing cytotoxicity and overcoming application restrictions. We summarize recent advances in T cell subset selection, CAR-T structural modifications, infiltration enhancement, genetic and metabolic interventions, production optimization, and the integration of novel technologies, presenting therapeutic approaches that could improve CAR-T cell therapy’s efficacy and applicability in solid tumors.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"7 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580062","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}
引用次数: 0
Prognostic impact of donor mitochondrial genomic variants in myelodysplastic neoplasms after stem-cell transplantation 供体线粒体基因组变异对干细胞移植后骨髓增生异常肿瘤的预后影响
IF 28.5 1区 医学
Journal of Hematology & Oncology Pub Date : 2024-11-04 DOI: 10.1186/s13045-024-01622-w
Jing Dong, Shahram Arsang-Jang, Tao Zhang, Zhongyuan Chen, Yung-Tsi Bolon, Stephen Spellman, Raul Urrutia, Paul Auer, Wael Saber
{"title":"Prognostic impact of donor mitochondrial genomic variants in myelodysplastic neoplasms after stem-cell transplantation","authors":"Jing Dong, Shahram Arsang-Jang, Tao Zhang, Zhongyuan Chen, Yung-Tsi Bolon, Stephen Spellman, Raul Urrutia, Paul Auer, Wael Saber","doi":"10.1186/s13045-024-01622-w","DOIUrl":"https://doi.org/10.1186/s13045-024-01622-w","url":null,"abstract":"Mitochondrial DNA (mtDNA) variants in patients with myelodysplastic neoplasms (MDS) are shown to be prognostic of outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). However, the prognostic impact of donor mtDNA variants is unknown. Here, we performed whole-genome sequencing on 494 donors who were matched to MDS patients enrolled in the Center for International Blood and Marrow Transplant Research (CIBMTR). We evaluated the impact of donor mtDNA variants on recipients’ transplantation outcomes, including overall survival, relapse, relapse-free survival, and transplant-related mortality. The optimism-adjusted bootstrap method was employed to evaluate the prognostic performance of models that include donor mtDNA variants alone and combined with MDS- and HCT-related clinical factors. In the entire donor cohort, we identified 1,825 mtDNA variants, including 67 potential pathogenic variants. Genetic variants on MT-CYB and MT-ND5 genes were identified as independent predictors of posttransplant outcomes. Integration of donor mtDNA variants into the models based on the International Prognostic Scoring System-Revised (IPSS-R) could capture more prognostic information for MDS patients. Sensitivity analysis in 397 unrelated donors obtained similar results. More importantly, we found that incorporating donor mtDNA variants with donor age and the degree of HLA-matching could help to identify “suboptimal” younger HLA-well-matched unrelated donors and “optimal” older HLA-partially/mismatched unrelated donors. Our study shows that mtDNA variants in donors, including those from unrelated donors, hold prognostic value for MDS patients undergoing allo-HCT and augment the prognostic stratification of current scoring systems. These findings present an opportunity to refine donor selection strategies and improve posttransplant outcomes for MDS patients.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"48 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574374","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}
引用次数: 0
Long-term survival with donor CD19 CAR-T cell treatment for relapsed patients after allogeneic hematopietic stem cell transplantation. 异基因造血干细胞移植后复发患者接受供体 CD19 CAR-T 细胞治疗后的长期存活率。
IF 29.5 1区 医学
Journal of Hematology & Oncology Pub Date : 2024-10-29 DOI: 10.1186/s13045-024-01626-6
Cheng Zhang, Xiaoqi Wang, Hai Yi, Yi Wang, Zhiling Yan, Jian Zhou, Ting Yang, Aibin Liang, Zhen Wang, Yingying Ma, Qin Wen, Lei Gao, Li Gao, Peiyan Kong, Xu Tan, Erlie Jiang, Xi Zhang
{"title":"Long-term survival with donor CD19 CAR-T cell treatment for relapsed patients after allogeneic hematopietic stem cell transplantation.","authors":"Cheng Zhang, Xiaoqi Wang, Hai Yi, Yi Wang, Zhiling Yan, Jian Zhou, Ting Yang, Aibin Liang, Zhen Wang, Yingying Ma, Qin Wen, Lei Gao, Li Gao, Peiyan Kong, Xu Tan, Erlie Jiang, Xi Zhang","doi":"10.1186/s13045-024-01626-6","DOIUrl":"10.1186/s13045-024-01626-6","url":null,"abstract":"<p><p>Chimeric Antigen Receptor T (CAR-T) cell therapy has significantly advanced in treating B-cell acute lymphoblastic leukemia (B-ALL) and has shown efficacy in managing relapsed B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor-derived CAR-T cell offer both high efficacy and rapid response. Although promising results exist, current research lacks definitive evidence of long-term survival benefits for patients treated with donor-derived CAR-T therapy. We report the long-term survival of 32 patients with post-transplant relapsed B-ALL treated with donor-derived CD19 CAR-T cell, achieving either complete Remission (CR) or CR with incomplete peripheral blood recovery (CRi). The median follow-up was 42 months, with 2-year overall survival (OS) and event-free survival (EFS) rates of 56.25% and 50.0%, respectively. The 5-year OS and EFS rates were 53.13% and 46.88%, with no new long-term adverse events observed. These findings demonstrate good long-term safety, supporting donor-derived CAR-T cell as a recommended treatment option for relapsed B-ALL patients post-transplantation. Trial registration: https://www.chictr.org.cn/showproj.html?proj=14315 . Registration number: ChiCTR-OOC-16008447.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":"103"},"PeriodicalIF":29.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522075","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}
引用次数: 0
Development and validation of the post-CAR prognostic index for large B-cell lymphoma patients after CAR-T progression in third or later line treatment. 开发并验证大 B 细胞淋巴瘤患者在 CAR-T 三线或三线以上治疗进展后的 CAR 后预后指数。
IF 29.5 1区 医学
Journal of Hematology & Oncology Pub Date : 2024-10-29 DOI: 10.1186/s13045-024-01608-8
Gloria Iacoboni, Víctor Navarro, Pierre Sesques, Kai Rejeski, Mariana Bastos-Oreiro, Fabio Serpenti, Ana Africa Martin Lopez, Josu Iraola-Truchuelo, Javier Delgado, Ariadna Perez, Manuel Guerreiro, Ana Carolina Caballero, Nuria Martinez-Cibrian, Hugo Luzardo Henriquez, Jose Maria Sanchez Pina, Juan-Manuel Sancho, Hervé Ghesquieres, Alberto Mussetti, Lucia Lopez Corral, Rafael Hernani, Juan Luis Reguera, Anna Sureda, Francesc Bosch, Alejandro Martin Garcia-Sancho, Mi Kwon, Marion Subklewe, Andrea Kuhnl, Emmanuel Bachy, Pere Barba, Guillermo Villacampa, Pau Abrisqueta
{"title":"Development and validation of the post-CAR prognostic index for large B-cell lymphoma patients after CAR-T progression in third or later line treatment.","authors":"Gloria Iacoboni, Víctor Navarro, Pierre Sesques, Kai Rejeski, Mariana Bastos-Oreiro, Fabio Serpenti, Ana Africa Martin Lopez, Josu Iraola-Truchuelo, Javier Delgado, Ariadna Perez, Manuel Guerreiro, Ana Carolina Caballero, Nuria Martinez-Cibrian, Hugo Luzardo Henriquez, Jose Maria Sanchez Pina, Juan-Manuel Sancho, Hervé Ghesquieres, Alberto Mussetti, Lucia Lopez Corral, Rafael Hernani, Juan Luis Reguera, Anna Sureda, Francesc Bosch, Alejandro Martin Garcia-Sancho, Mi Kwon, Marion Subklewe, Andrea Kuhnl, Emmanuel Bachy, Pere Barba, Guillermo Villacampa, Pau Abrisqueta","doi":"10.1186/s13045-024-01608-8","DOIUrl":"10.1186/s13045-024-01608-8","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. After CAR-T failure, survival outcomes are heterogeneous and a prognostic model in this patient population is lacking. A training cohort of 216 patients with progressive disease (PD) after CAR-T from 12 Spanish centers was used to develop the Post-CAR Prognostic Index (PC-PI); primary endpoint was overall survival (OS) from CAR-T progression. Validation was performed in an external cohort from three different European centers (n = 204). The prognostic score incorporated five variables, assessed at time of PD to CAR-T: ECOG (> 0), hemoglobin (< 10 g/dL), LDH (≥ 2xULN), number of extranodal sites (> 1) and time from CAR-T to PD (< 4 months). Patients were classified in four risk groups with distinct OS (p-value < 0.05 in all comparisons). In the validation cohort, median OS in the low (31%), intermediate-low (26%), intermediate-high (17%) and high risk (26%) were 15.7, 7.1, 1.8 and 1.0 months, respectively (p < 0.05 in all comparisons). Results were consistent following adjustment for subsequent treatment. In the external cohort, the PC-PI showed a C-statistic of 0.79 (95%CI 0.76-0.82), outperforming IPI and R-IPI. In conclusion, the PC-PI score is a novel tool for OS prediction and could facilitate risk-adapted management of LBCL patients relapsing after CAR T-cells. Additionally, these results will help stratification and interpretation of trials and real-world data incorporating CART-exposed patients.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":"102"},"PeriodicalIF":29.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522074","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}
引用次数: 0
Tucidinostat plus pediatric-inspired chemotherapy for newly diagnosed adult ETP-ALL/LBL: a single-arm, phase 2 trial 针对新诊断出的成人ETP-ALL/LBL的土西地诺他特加儿科启发化疗:单臂2期试验
IF 28.5 1区 医学
Journal of Hematology & Oncology Pub Date : 2024-10-28 DOI: 10.1186/s13045-024-01624-8
Jieping Lin, Zicong Huang, Zihong Cai, Jia Li, Zhen Li, Chenhao Ding, Zhixiang Wang, Xiaofang Li, Xuan Zhou, Bailin He, Wenhao Zhong, Li Xuan, Qifa Liu, Yang Xu, Hongsheng Zhou
{"title":"Tucidinostat plus pediatric-inspired chemotherapy for newly diagnosed adult ETP-ALL/LBL: a single-arm, phase 2 trial","authors":"Jieping Lin, Zicong Huang, Zihong Cai, Jia Li, Zhen Li, Chenhao Ding, Zhixiang Wang, Xiaofang Li, Xuan Zhou, Bailin He, Wenhao Zhong, Li Xuan, Qifa Liu, Yang Xu, Hongsheng Zhou","doi":"10.1186/s13045-024-01624-8","DOIUrl":"https://doi.org/10.1186/s13045-024-01624-8","url":null,"abstract":"Early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is a distinct subtype of T-ALL/LBL, characterized by a poor response to initial chemotherapy, a high relapse rate, and an inferior outcome. The treatment options for ETP-ALL/LBL are currently limited, and there are no reported clinical trials available for ETP-ALL/LBL. From June 2018 to June 2022, we conducted a single-arm, single-center, phase 2 trial (NCT03553238) in newly diagnosed ETP-ALL/LBL (age 14–55). Patients (N = 54) received pediatric-inspired chemotherapy plus tucidinostat, which was orally administered once daily at a dosage of 10 mg from induction to consolidation therapy. The primary endpoint was 3 year event-free survival (EFS). Secondary endpoints were overall survival (OS), relapse-free survival (RFS), complete remission rate and adverse events. The composite complete remission (CRc, complete response [CR] plus complete response with incomplete blood count recovery [CRi]) rate and MRD negativity after induction therapy was 91% (49 of 54 patients) and 65% (35 of 54 patients), respectively. The MRD negativity after consolidation was achieved in 87% patients (47 of 54 patients). With a median follow-up of 39.3 months (IQR, 20.6 to 60.0), the 3 year EFS rate was 67.7% (95% CI 56.2–81.7), the 3 year OS rate was 71.5% (95% CI 60.2–84.9) and the 3 year RFS rate was 67.5% (95% CI 55.9–81.6). The most common grade 3–4 adverse events were neutropenia (94%), anemia (85%), thrombocytopenia (76%), and infection (53%). Tucidinostat plus pediatric regimen is an effective and well-tolerated regimen for new diagnosed ETP-ALL/LBL, with high CRc and MRD negativity rates, as well as encouraging survival outcomes.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"75 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519316","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}
引用次数: 0
Predictive value of tumor microenvironment on pathologic response to neoadjuvant chemotherapy in patients with undifferentiated pleomorphic sarcomas 肿瘤微环境对未分化多形性肉瘤患者新辅助化疗病理反应的预测价值
IF 28.5 1区 医学
Journal of Hematology & Oncology Pub Date : 2024-10-23 DOI: 10.1186/s13045-024-01614-w
Jean Philippe Guegan, Nathan El Ghazzi, Julien Vibert, Christophe Rey, Lucile Vanhersecke, Jean Michel Coindre, Maud Toulmonde, Mariella Spalato Ceruso, Florent Peyraud, Alban Bessede, Antoine Italiano
{"title":"Predictive value of tumor microenvironment on pathologic response to neoadjuvant chemotherapy in patients with undifferentiated pleomorphic sarcomas","authors":"Jean Philippe Guegan, Nathan El Ghazzi, Julien Vibert, Christophe Rey, Lucile Vanhersecke, Jean Michel Coindre, Maud Toulmonde, Mariella Spalato Ceruso, Florent Peyraud, Alban Bessede, Antoine Italiano","doi":"10.1186/s13045-024-01614-w","DOIUrl":"https://doi.org/10.1186/s13045-024-01614-w","url":null,"abstract":"Undifferentiated pleomorphic sarcomas (UPS) represent a prevalent and aggressive subtype of soft tissue sarcomas (STS) in adults. Despite advancements in loco regional treatments, many patients with high grade STS, including UPS, develop metastatic disease. Neoadjuvant chemotherapy is a standard approach to mitigate this risk, but response variability necessitates refined patient selection strategies. This study investigated the correlation between UPS microenvironment and neoadjuvant chemotherapy response in resectable UPS. The NEOSARCOMICS study (NCT02789384) enrolled patients with resectable STS from six sarcoma centers in France. Patients received anthracycline based chemotherapy, followed by surgery. Histological response, gene expression profiling, and multiplex immunohistofluorescence were performed on baseline and post treatment tumor samples. Plasma proteomics was analyzed to identify biomarkers. Good responders to neoadjuvant chemotherapy showed enrichment in genes related to stemness and cell cycle regulation, while poor responders exhibited immune related gene enrichment. Proteomic profiling revealed immune pathway activation and downregulation of cell cycle pathways in non responders. Despite being associated with a good prognosis, high immune infiltration, particularly of CD8 + T cells and CD20 + B cells, predicts a poor response to neoadjuvant chemotherapy in UPS, suggesting the need for alternative therapeutic strategies for patients with inflamed UPS.Ongoing clinical trials are exploring the efficacy of combining chemotherapy with immune checkpoint inhibitors to improve outcomes.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"4 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488925","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}
引用次数: 0
Global cancer statistics for adolescents and young adults: population based study 全球青少年和年轻成人癌症统计数据:基于人口的研究
IF 28.5 1区 医学
Journal of Hematology & Oncology Pub Date : 2024-10-21 DOI: 10.1186/s13045-024-01623-9
Wangzhong Li, Hengrui Liang, Wei Wang, Jun Liu, Xiwen Liu, Shen Lao, Wenhua Liang, Jianxing He
{"title":"Global cancer statistics for adolescents and young adults: population based study","authors":"Wangzhong Li, Hengrui Liang, Wei Wang, Jun Liu, Xiwen Liu, Shen Lao, Wenhua Liang, Jianxing He","doi":"10.1186/s13045-024-01623-9","DOIUrl":"https://doi.org/10.1186/s13045-024-01623-9","url":null,"abstract":"Accurate and up-to-date estimates of the global cancer burden in adolescents and young adults (AYA) are scarce. This study aims to assess the global burden and trends of AYA cancer, with a focus on socioeconomic disparities, to inform global cancer control strategies. AYA cancer, defined as cancer occurring in individuals aged 15–39, was analyzed using data from the Global Burden of Disease (GBD) 2021 study and the Global Cancer Observatory (GLOBOCAN) 2022 project. We examined the global burden by age, sex, geographic location, and Human Development Index (HDI), as well as its temporal trends. Primary outcomes included age-standardized incidence and mortality rates (ASIR, ASMR) and the average annual percent change (AAPC). In 2022, an estimated 1,300,196 incidental cases and 377,621 cancer-related deaths occurred among AYAs worldwide, with an ASIR of 40.3 per 100,000 and an ASMR of 11.8 per 100,000. The most common cancers were breast, thyroid, and cervical, while the leading causes of death were breast, cervical, and leukemia. The incidence and mortality were disproportionately higher among females (ASIR: 52.9 for females vs. 28.3 for males; ASMR: 13.1 for females vs. 10.6 for males). Countries with higher HDI experienced a higher incidence of AYA cancers (ASIR: 32.0 [low HDI] vs. 54.8 [very high HDI]), while countries with lower HDI faced a disproportionately higher mortality burden (ASMR: 17.2 [low HDI] vs. 8.4 [very high HDI]) despite their relatively low incidence. Disproportionality and regression measures highlighted significant HDI-related inequalities. AYA cancer incidence was stable from 2000 to 2011 (AAPC: − 0.04) but increased from 2012 to 2021 (AAPC: 0.53), driven by growing gonadal and colorectal cancers. Mortality decreased substantially from 2000 to 2011 (AAPC: − 1.64), but the decline slowed from 2012 (AAPC: − 0.32) probably due to increased deaths from gonadal cancers. These trends varied by sex, cancer type, geography, and HDI. AYA cancers present a significant and growing global burden, with marked disparities across sex, geographic locations, and HDI levels. Policymakers should prioritize equitable resource allocation and implement targeted interventions to reduce these inequalities, particularly in low-HDI regions and with regard to gonadal cancers.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"67 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452124","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}
引用次数: 0
Correction: Phase IB part of LOC-R01, a LOC network non-comparative randomized phase IB/II study testing R-MPV in combination with escalating doses of lenalidomide or ibrutinib for newly diagnosed primary central nervous system lymphoma (PCNSL) patients 更正:LOC-R01的IB期部分,这是一项LOC网络非比较性随机IB/II期研究,测试R-MPV与来那度胺或伊布替尼联合治疗新诊断的原发性中枢神经系统淋巴瘤(PCNSL)患者的效果。
IF 28.5 1区 医学
Journal of Hematology & Oncology Pub Date : 2024-10-19 DOI: 10.1186/s13045-024-01620-y
Marion Alcantara, Marion Chevrier, Fabrice Jardin, Anna Schmitt, Caroline Houillier, Lucie Oberic, Olivier Chinot, Franck Morschhauser, Frédéric Peyrade, Roch Houot, Khê Hoang-Xuan, Hervé Ghesquieres, Carole Soussain
{"title":"Correction: Phase IB part of LOC-R01, a LOC network non-comparative randomized phase IB/II study testing R-MPV in combination with escalating doses of lenalidomide or ibrutinib for newly diagnosed primary central nervous system lymphoma (PCNSL) patients","authors":"Marion Alcantara, Marion Chevrier, Fabrice Jardin, Anna Schmitt, Caroline Houillier, Lucie Oberic, Olivier Chinot, Franck Morschhauser, Frédéric Peyrade, Roch Houot, Khê Hoang-Xuan, Hervé Ghesquieres, Carole Soussain","doi":"10.1186/s13045-024-01620-y","DOIUrl":"https://doi.org/10.1186/s13045-024-01620-y","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction: Journal of Hematology &amp; Oncology (2024) 17:86&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;https://doi.org/10.1186/s13045-024-01606-w&lt;/b&gt;&lt;/p&gt;&lt;p&gt;The authors’ names in the authorship of the original article were mistakenly inverted and have since been amended.&lt;/p&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;CellAction, Center for Cancer Immunotherapy, Institut Curie, Suresnes, France&lt;/p&gt;&lt;p&gt;Marion Alcantara&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Clinical Hematology Unit, Institut Curie, Saint-Cloud, 92210, France&lt;/p&gt;&lt;p&gt;Marion Alcantara &amp; Carole Soussain&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Biostatistics, Institut Curie, Saint-Cloud, 92210, France&lt;/p&gt;&lt;p&gt;Marion Chevrier&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Clinical Hematology and INSERM U1245, Centre Henri Becquerel, Rouen, France&lt;/p&gt;&lt;p&gt;Fabrice Jardin&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Service d’Hématologie, Institut Bergonié, Bordeaux, France&lt;/p&gt;&lt;p&gt;Anna Schmitt&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Neurooncology Department, Assistance Publique – Hôpitaux de Paris (APHP), Sorbonne Université, IHU, ICM, Groupe Hospitalier Pitié-Salpêtrière, Paris, France&lt;/p&gt;&lt;p&gt;Caroline Houillier &amp; Khê Hoang-Xuan&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Hematology, Institut Universitaire du Cancer de Toulouse Oncopôle, Toulouse, France&lt;/p&gt;&lt;p&gt;Lucie Oberic&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;AP-HM, Service de Neuro-Oncologie, CHU de la Timone, Aix-Marseille Université, CNRS, INP, Marseille Cedex, France&lt;/p&gt;&lt;p&gt;Olivier Chinot&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Univ. Lille, CHU Lille, ULR 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, F-59000, France&lt;/p&gt;&lt;p&gt;Franck Morschhauser&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Service d’Onco-hématologie, Centre Hospitalier Simone Veil, Cannes, France&lt;/p&gt;&lt;p&gt;Frédéric Peyrade&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Hematology, University Hospital of Rennes, UMR U1236, INSERM, University of Rennes, French Blood Establishment, Rennes, France&lt;/p&gt;&lt;p&gt;Roch Houot&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Hematology, Hôpital Lyon Sud, Claude Bernard Lyon 1 University, Pierre- Bénite, France&lt;/p&gt;&lt;p&gt;Hervé Ghesquieres&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Center for Cancer Immunotherapy, Institut Curie, PSL Research University, INSERM U932, Paris, 75005, France&lt;/p&gt;&lt;p&gt;Carole Soussain&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;span&gt;Authors&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;Marion Alcantara&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Marion Chevrier&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Fabrice Jardin&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Anna Schmitt&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Caroline Houillier&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Lucie Oberic&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;s","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"14 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451419","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}
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