Swati Naik, Ying Li, Aimee C. Talleur, Subodh Selukar, Emily Ashcraft, Cheng Cheng, Renee M. Madden, Ewelina Mamcarz, Amr Qudeimat, Akshay Sharma, Ashok Srinivasan, Ali Y. Suliman, Rebecca Epperly, Esther A. Obeng, M. Paulina Velasquez, Deanna Langfitt, Sarah Schell, Jean-Yves Métais, Paula Y. Arnold, Diego R. Hijano, Gabriela Maron, Thomas E. Merchant, Salem Akel, Wing Leung, Stephen Gottschalk, Brandon M. Triplett
{"title":"Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial","authors":"Swati Naik, Ying Li, Aimee C. Talleur, Subodh Selukar, Emily Ashcraft, Cheng Cheng, Renee M. Madden, Ewelina Mamcarz, Amr Qudeimat, Akshay Sharma, Ashok Srinivasan, Ali Y. Suliman, Rebecca Epperly, Esther A. Obeng, M. Paulina Velasquez, Deanna Langfitt, Sarah Schell, Jean-Yves Métais, Paula Y. Arnold, Diego R. Hijano, Gabriela Maron, Thomas E. Merchant, Salem Akel, Wing Leung, Stephen Gottschalk, Brandon M. Triplett","doi":"10.1186/s13045-024-01567-0","DOIUrl":"https://doi.org/10.1186/s13045-024-01567-0","url":null,"abstract":"Relapse remains a challenge after transplantation in pediatric patients with hematological malignancies. Myeloablative regimens used for disease control are associated with acute and long-term adverse effects. We used a CD45RA-depleted haploidentical graft for adoptive transfer of memory T cells combined with NK-cell addback and hypothesized that maximizing the graft-versus-leukemia (GVL) effect might allow for reduction in intensity of conditioning regimen. In this phase II clinical trial (NCT01807611), 72 patients with hematological malignancies (complete remission (CR)1: 25, ≥ CR2: 28, refractory disease: 19) received haploidentical CD34 + enriched and CD45RA-depleted hematopoietic progenitor cell grafts followed by NK-cell infusion. Conditioning included fludarabine, thiotepa, melphalan, cyclophosphamide, total lymphoid irradiation, and graft-versus-host disease (GVHD) prophylaxis consisted of a short-course sirolimus or mycophenolate mofetil without serotherapy. The 3-year overall survival (OS) and event-free-survival (EFS) for patients in CR1 were 92% (95% CI:72–98) and 88% (95% CI: 67–96); ≥ CR2 were 81% (95% CI: 61–92) and 68% (95% CI: 47–82) and refractory disease were 32% (95% CI: 11–54) and 20% (95% CI: 6–40). The 3-year EFS for all patients in morphological CR was 77% (95% CI: 64–87) with no difference amongst recipients with or without minimal residual disease (P = 0.2992). Immune reconstitution was rapid, with mean CD3 and CD4 T-cell counts of 410/μL and 140/μL at day + 30. Cumulative incidence of acute GVHD and chronic GVHD was 36% and 26% but most patients with acute GVHD recovered rapidly with therapy. Lower rates of grade III-IV acute GVHD were observed with NK-cell alloreactive donors (P = 0.004), and higher rates of moderate/severe chronic GVHD occurred with maternal donors (P = 0.035). The combination of a CD45RA-depleted graft and NK-cell addback led to robust immune reconstitution maximizing the GVL effect and allowed for use of a submyeloablative, TBI-free conditioning regimen that was associated with excellent EFS resulting in promising long-term outcomes in this high-risk population. The trial is registered at ClinicalTrials.gov (NCT01807611).","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"5 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461895","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":"Advances in CAR-T-cell therapy in T-cell malignancies","authors":"Rubing Zheng, Xiaojian Zhu, Yi Xiao","doi":"10.1186/s13045-024-01568-z","DOIUrl":"https://doi.org/10.1186/s13045-024-01568-z","url":null,"abstract":"Significant advances have been made in chimeric antigen receptor T (CAR-T)-cell therapy for the treatment of recurrent or refractory B-cell hematologic malignancies. However, CAR-T-cell therapy has not yet achieved comparable success in the management of aggressive T-cell malignancies. This article reviews the challenges of CAR-T-cell therapy in treating T-cell malignancies and summarizes the progress of preclinical and clinical studies in this area. We present an analysis of clinical trials of CAR-T-cell therapies for the treatment of T-cell malignancies grouped by target antigen classification. Moreover, this review focuses on the major challenges encountered by CAR-T-cell therapies, including the nonspecific killing due to T-cell target antigen sharing and contamination with cell products during preparation. This review discusses strategies to overcome these challenges, presenting novel therapeutic approaches that could enhance the efficacy and applicability of CAR-T-cell therapy in the treatment of T-cell malignancies. These ideas and strategies provide important information for future studies to promote the further development and application of CAR-T-cell therapy in this field.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"7 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141444821","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":"Individualized dynamic frailty-tailored therapy (DynaFiT) in elderly patients with newly diagnosed multiple myeloma: a prospective study","authors":"Yingjie Zhang, Xinyue Liang, Weiling Xu, Xingcheng Yi, Rui Hu, Xintian Ma, Yurong Yan, Nan Zhang, Jingxuan Wang, Xiaoxiao Sun, Yufeng Zhu, Mengru Tian, Maozhuo Lan, Mengtuan Long, Yun Dai, Fengyan Jin","doi":"10.1186/s13045-024-01569-y","DOIUrl":"https://doi.org/10.1186/s13045-024-01569-y","url":null,"abstract":"It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle. Of 90 patients, 33 (37%), 16 (18%), and 41 (45%) were fit, intermediate fit, and frail at baseline, respectively. Of 75 patients who had geriatric assessment at least twice, 28 (37%) experienced frailty category changes at least once. At analysis, 15/26 (58%) frail patients improved (27% became fit and 31% became intermediate fit), 4/15 (27%) intermediate fit patients either improved or deteriorated (two for each), and 6/30 (20%) fit patients deteriorated. During induction, 34/90 (38%) patients discontinued treatment, including 10/33 (30%) fit, 4/16 (25%) intermediate fit, and 20/41 (49%) frail; 14/40 (35%) frail patients discontinued treatment within the first two cycles, mainly because of non-hematologic toxicity (mostly infections). For fit, intermediate-fit, and frail patients, the overall response rate was 100%, 93%, and 73%, respectively; one-year overall survival was 90%, 75%, and 54%, respectively. Therefore, the individualized DynaFiT is feasible and promising for heterogeneous elderly patients.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"31 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141444919","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}
Yan Bian, Ye Gao, Han Lin, Chang Sun, Wei Wang, Siyu Sun, Xiuling Li, Zhijie Feng, Jianlin Ren, Hezhong Chen, Chaojing Lu, Jinfang Xu, Jun Zhou, Kangkang Wan, Lei Xin, Zhaoshen Li, Luowei Wang
{"title":"Non-invasive diagnosis of esophageal cancer by a simplified circulating cell-free DNA methylation assay targeting OTOP2 and KCNA3: a double-blinded, multicenter, prospective study.","authors":"Yan Bian, Ye Gao, Han Lin, Chang Sun, Wei Wang, Siyu Sun, Xiuling Li, Zhijie Feng, Jianlin Ren, Hezhong Chen, Chaojing Lu, Jinfang Xu, Jun Zhou, Kangkang Wan, Lei Xin, Zhaoshen Li, Luowei Wang","doi":"10.1186/s13045-024-01565-2","DOIUrl":"10.1186/s13045-024-01565-2","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named \"IEsohunter\") for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance.</p><p><strong>Methods: </strong>Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC.</p><p><strong>Results: </strong>We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880-0.927) and 0.727 (95% CI 0.653-0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1-85.6), 87.3% (95% CI 79.4-92.4), 92.5% (95% CI 85.9-96.2), and 96.9% (95% CI 84.3-99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4-90.6) and specificity of 93.3% (95% CI 91.2-94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC.</p><p><strong>Conclusions: </strong>The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":"47"},"PeriodicalIF":29.5,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419486","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}
Pan Song, Zirui Gao, Yige Bao, Li Chen, Yuhe Huang, Yanyan Liu, Qiang Dong, Xiawei Wei
{"title":"Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy","authors":"Pan Song, Zirui Gao, Yige Bao, Li Chen, Yuhe Huang, Yanyan Liu, Qiang Dong, Xiawei Wei","doi":"10.1186/s13045-024-01563-4","DOIUrl":"https://doi.org/10.1186/s13045-024-01563-4","url":null,"abstract":"The Wnt/β-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal physiological conditions, the Wnt/β-catenin signaling pathway is meticulously regulated. However, aberrant activation of this pathway and downstream target genes can occur due to mutations in key components of the Wnt/β-catenin pathway, epigenetic modifications, and crosstalk with other signaling pathways. Consequently, these dysregulations contribute significantly to tumor initiation and progression. Therapies targeting the Wnt/β-catenin signaling transduction have exhibited promising prospects and potential for tumor treatment. An increasing number of medications targeting this pathway are continuously being developed and validated. This comprehensive review aims to summarize the latest advances in our understanding of the role played by the Wnt/β-catenin signaling pathway in carcinogenesis and targeted therapy, providing valuable insights into acknowledging current opportunities and challenges associated with targeting this signaling pathway in cancer research and treatment.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"54 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334440","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}
Dafei Chai, Junhao Wang, Chunmei Fan, Jing-Ming Lim, Xu Wang, Praveen Neeli, Xinfang Yu, Ken H. Young, Yong Li
{"title":"Remodeling of anti-tumor immunity with antibodies targeting a p53 mutant","authors":"Dafei Chai, Junhao Wang, Chunmei Fan, Jing-Ming Lim, Xu Wang, Praveen Neeli, Xinfang Yu, Ken H. Young, Yong Li","doi":"10.1186/s13045-024-01566-1","DOIUrl":"https://doi.org/10.1186/s13045-024-01566-1","url":null,"abstract":"p53, the most frequently mutated gene in cancer, lacks effective targeted drugs. We developed monoclonal antibodies (mAbs) that target a p53 hotspot mutation E285K without cross-reactivity with wild-type p53. They were delivered using lipid nanoparticles (LNPs) that encapsulate DNA plasmids. Western blot, BLI, flow cytometry, single-cell sequencing (scRNA-seq), and other methods were employed to assess the function of mAbs in vitro and in vivo. These LNP-pE285K-mAbs in the IgG1 format exhibited a robust anti-tumor effect, facilitating the infiltration of immune cells, including CD8+ T, B, and NK cells. scRNA-seq revealed that IgG1 reduces immune inhibitory signaling, increases MHC signaling from B cells to CD8+ T cells, and enriches anti-tumor T cell and B cell receptor profiles. The E285K-mAbs were also produced in the dimeric IgA (dIgA) format, whose anti-tumor activity depended on the polymeric immunoglobulin receptor (PIGR), a membrane Ig receptor, whereas that of IgG1 relied on TRIM21, an intracellular IgG receptor. Targeting specific mutant epitopes using DNA-encoded and LNP-delivered mAbs represents a potential precision medicine strategy against p53 mutants in TRIM21- or PIGR-positive cancers.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"43 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334445","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}
Belén Toledo, Linrui Zhu Chen, María Paniagua-Sancho, Juan Antonio Marchal, Macarena Perán, Elisa Giovannetti
{"title":"Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy","authors":"Belén Toledo, Linrui Zhu Chen, María Paniagua-Sancho, Juan Antonio Marchal, Macarena Perán, Elisa Giovannetti","doi":"10.1186/s13045-024-01559-0","DOIUrl":"https://doi.org/10.1186/s13045-024-01559-0","url":null,"abstract":"Macrophages infiltrating tumour tissues or residing in the microenvironment of solid tumours are known as tumour-associated macrophages (TAMs). These specialized immune cells play crucial roles in tumour growth, angiogenesis, immune regulation, metastasis, and chemoresistance. TAMs encompass various subpopulations, primarily classified into M1 and M2 subtypes based on their differentiation and activities. M1 macrophages, characterized by a pro-inflammatory phenotype, exert anti-tumoural effects, while M2 macrophages, with an anti-inflammatory phenotype, function as protumoural regulators. These highly versatile cells respond to stimuli from tumour cells and other constituents within the tumour microenvironment (TME), such as growth factors, cytokines, chemokines, and enzymes. These stimuli induce their polarization towards one phenotype or another, leading to complex interactions with TME components and influencing both pro-tumour and anti-tumour processes. This review comprehensively and deeply covers the literature on macrophages, their origin and function as well as the intricate interplay between macrophages and the TME, influencing the dual nature of TAMs in promoting both pro- and anti-tumour processes. Moreover, the review delves into the primary pathways implicated in macrophage polarization, examining the diverse stimuli that regulate this process. These stimuli play a crucial role in shaping the phenotype and functions of macrophages. In addition, the advantages and limitations of current macrophage based clinical interventions are reviewed, including enhancing TAM phagocytosis, inducing TAM exhaustion, inhibiting TAM recruitment, and polarizing TAMs towards an M1-like phenotype. In conclusion, while the treatment strategies targeting macrophages in precision medicine show promise, overcoming several obstacles is still necessary to achieve an accessible and efficient immunotherapy.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"18 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304498","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}
Tobias Ronny Haage, Emmanouil Charakopoulos, Vikas Bhuria, Conny K Baldauf, Mark Korthals, Juliane Handschuh, Peter Müller, Juan Li, Kunjan Harit, Gopala Nishanth, Stephanie Frey, Martin Böttcher, Klaus-Dieter Fischer, Jan Dudeck, Anne Dudeck, Daniel B Lipka, Burkhart Schraven, Anthony R Green, Andreas J Müller, Dimitrios Mougiakakos, Thomas Fischer
{"title":"Neutrophil-specific expression of JAK2-V617F or CALRmut induces distinct inflammatory profiles in myeloproliferative neoplasia.","authors":"Tobias Ronny Haage, Emmanouil Charakopoulos, Vikas Bhuria, Conny K Baldauf, Mark Korthals, Juliane Handschuh, Peter Müller, Juan Li, Kunjan Harit, Gopala Nishanth, Stephanie Frey, Martin Böttcher, Klaus-Dieter Fischer, Jan Dudeck, Anne Dudeck, Daniel B Lipka, Burkhart Schraven, Anthony R Green, Andreas J Müller, Dimitrios Mougiakakos, Thomas Fischer","doi":"10.1186/s13045-024-01562-5","DOIUrl":"10.1186/s13045-024-01562-5","url":null,"abstract":"<p><strong>Background: </strong>Neutrophils play a crucial role in inflammation and in the increased thrombotic risk in myeloproliferative neoplasms (MPNs). We have investigated how neutrophil-specific expression of JAK2-V617F or CALRdel re-programs the functions of neutrophils.</p><p><strong>Methods: </strong>Ly6G-Cre JAK2-V617F and Ly6G-Cre CALRdel mice were generated. MPN parameters as blood counts, splenomegaly and bone marrow histology were compared to wild-type mice. Megakaryocyte differentiation was investigated using lineage-negative bone marrow cells upon in vitro incubation with TPO/IL-1β. Cytokine concentrations in serum of mice were determined by Mouse Cytokine Array. IL-1α expression in various hematopoietic cell populations was determined by intracellular FACS analysis. RNA-seq to analyse gene expression of inflammatory cytokines was performed in isolated neutrophils from JAK2-V617F and CALR-mutated mice and patients. Bioenergetics of neutrophils were recorded on a Seahorse extracellular flux analyzer. Cell motility of neutrophils was monitored in vitro (time lapse microscopy), and in vivo (two-photon microscopy) upon creating an inflammatory environment. Cell adhesion to integrins, E-selectin and P-selection was investigated in-vitro. Statistical analysis was carried out using GraphPad Prism. Data are shown as mean ± SEM. Unpaired, two-tailed t-tests were applied.</p><p><strong>Results: </strong>Strikingly, neutrophil-specific expression of JAK2-V617F, but not CALRdel, was sufficient to induce pro-inflammatory cytokines including IL-1 in serum of mice. RNA-seq analysis in neutrophils from JAK2-V617F mice and patients revealed a distinct inflammatory chemokine signature which was not expressed in CALR-mutant neutrophils. In addition, IL-1 response genes were significantly enriched in neutrophils of JAK2-V617F patients as compared to CALR-mutant patients. Thus, JAK2-V617F positive neutrophils, but not CALR-mutant neutrophils, are pathogenic drivers of inflammation in MPN. In line with this, expression of JAK2-V617F or CALRdel elicited a significant difference in the metabolic phenotype of neutrophils, suggesting a stronger inflammatory activity of JAK2-V617F cells. Furthermore, JAK2-V617F, but not CALRdel, induced a VLA4 integrin-mediated adhesive phenotype in neutrophils. This resulted in reduced neutrophil migration in vitro and in an inflamed vessel. This mechanism may contribute to the increased thrombotic risk of JAK2-V617F patients compared to CALR-mutant individuals.</p><p><strong>Conclusions: </strong>Taken together, our findings highlight genotype-specific differences in MPN-neutrophils that have implications for the differential pathophysiology of JAK2-V617F versus CALR-mutant disease.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":"43"},"PeriodicalIF":29.5,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11163796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296210","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":"Ferroptosis: principles and significance in health and disease","authors":"Fangquan Chen, Rui Kang, Daolin Tang, Jiao Liu","doi":"10.1186/s13045-024-01564-3","DOIUrl":"https://doi.org/10.1186/s13045-024-01564-3","url":null,"abstract":"Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed by molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic cell death pathway in 2012, ferroptosis has emerged as a crucial mechanism in numerous physiological and pathological contexts, leading to significant therapeutic advancements across a wide range of diseases. This review summarizes the fundamental molecular mechanisms and regulatory pathways underlying ferroptosis, including both GPX4-dependent and -independent antioxidant mechanisms. Additionally, we examine the involvement of ferroptosis in various pathological conditions, including cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, and metabolic disorders. Specifically, we explore the role of ferroptosis in response to chemotherapy, radiotherapy, immunotherapy, nanotherapy, and targeted therapy. Furthermore, we discuss pharmacological strategies for modulating ferroptosis and potential biomarkers for monitoring this process. Lastly, we elucidate the interplay between ferroptosis and other forms of regulated cell death. Such insights hold promise for advancing our understanding of ferroptosis in the context of human health and disease.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"14 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264892","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}
Saurabh Zanwar, Surbhi Sidana, Leyla Shune, Omar Castaneda Puglianini, Oren Pasvolsky, Rebecca Gonzalez, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, James A. Davis, Megan Herr, Hamza Hashmi, Peter Forsberg, Douglas Sborov, Larry D. Anderson Jr, Joseph P. McGuirk, Charlotte Wagner, Alex Lieberman-Cribbin, Adriana Rossi, Ciara L. Freeman, Frederick L. Locke, Shambavi Richard, Jack Khouri, Yi Lin, Krina K. Patel, Shaji K. Kumar, Doris K. Hansen
{"title":"Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel","authors":"Saurabh Zanwar, Surbhi Sidana, Leyla Shune, Omar Castaneda Puglianini, Oren Pasvolsky, Rebecca Gonzalez, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, James A. Davis, Megan Herr, Hamza Hashmi, Peter Forsberg, Douglas Sborov, Larry D. Anderson Jr, Joseph P. McGuirk, Charlotte Wagner, Alex Lieberman-Cribbin, Adriana Rossi, Ciara L. Freeman, Frederick L. Locke, Shambavi Richard, Jack Khouri, Yi Lin, Krina K. Patel, Shaji K. Kumar, Doris K. Hansen","doi":"10.1186/s13045-024-01555-4","DOIUrl":"https://doi.org/10.1186/s13045-024-01555-4","url":null,"abstract":"Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions. Visceral or soft tissue lesions non-contiguous from bone was classified as EMD. Time-to-event analyses were performed from date of ide-cel infusion. Among 351 patients, 84 (24%) had EMD prior to infusion. The median follow-up from ide-cel infusion was 18.2 months (95% CI: 17-19.3). The day 90 overall response rates (ORR) were 52% vs. 82% for the EMD and non-EMD cohorts, respectively (p < 0.001). The median progression-free survival (PFS) was 5.3 months (95% CI: 4.1–6.9) for the EMD cohort vs. 11.1 months (95% CI: 9.2–12.6; p < 0.0001) for the non-EMD cohort. In a multivariable analysis, EMD was an independent predictor of inferior PFS [hazard ratio 1.5 (1.1–2.2), p = 0.02]. The median overall survival was 14.8 months [95% CI: 9-Not reached (NR)] vs. 26.9 months (26.3 vs. NR, p = 0.006) for the EMD and non-EMD cohorts, respectively. Extramedullary disease represents an independent predictor of inferior day 90 ORR and PFS among patients treated with ide-cel.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"27 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264931","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}