Frontiers in hematology最新文献_第2页

Research and clinical updates on IRAK4 and its roles in inflammation and malignancy: themes and highlights from the 1st symposium on IRAK4 in cancer 有关 IRAK4 及其在炎症和恶性肿瘤中作用的研究和临床最新进展：第一届癌症中的 IRAK4 研讨会的主题和亮点

Frontiers in hematology Pub Date : 2024-02-15 DOI: 10.3389/frhem.2024.1339870

Guillermo Garcia-Manero, Uwe Platzbecker, Kian-Huat Lim, Grzegorz Nowakowski, Omar Abdel-Wahab, Hagop Kantarjian, Amit Verma, D. Starczynowski

{"title":"Research and clinical updates on IRAK4 and its roles in inflammation and malignancy: themes and highlights from the 1st symposium on IRAK4 in cancer","authors":"Guillermo Garcia-Manero, Uwe Platzbecker, Kian-Huat Lim, Grzegorz Nowakowski, Omar Abdel-Wahab, Hagop Kantarjian, Amit Verma, D. Starczynowski","doi":"10.3389/frhem.2024.1339870","DOIUrl":"https://doi.org/10.3389/frhem.2024.1339870","url":null,"abstract":"The intracellular serine/threonine interleukin 1 receptor-associated kinase 4 (IRAK4) is necessary for most signaling by activated Toll-like receptors (TLRs). Activation of IRAK4 drives activation of nuclear factor kappa B (NF-κB) and so promotes cell survival, inflammation, and other aspects of the adaptive immune response. However, the IRAK4 pathway can be coopted by cancers and lead to the survival and proliferation of malignant cells. Inappropriate IRAK4 activity has been linked with the progression of myelodysplastic syndrome (MDS), other hematologic malignancies, and some solid tumors, and preclinical cancer models indicate that IRAK4 inhibition has anti-tumor effects. As such, inhibition of IRAK4 is an emerging and attractive target for tumor suppression. The growing interest in IRAK4 motivated the 1st Symposium on IRAK4 in Cancer held in October 2022 to bring together IRAK4 researchers and clinicians to discuss new insights into the biology of IRAK4 and development of IRAK4 inhibitors. Presentations and discussions at the meeting provided updates on the biology of IRAK4 and its links with mutations in the spliceosome, new outcomes from preclinical models that indicate synergy between inhibitors of IRAK4 and FLT3 and BTK inhibitors, and an update on the clinical development of the investigational IRAK4 inhibitor emavusertib, currently being assessed in ongoing phase 1/2 clinical studies in hematologic cancers and several solid tumors.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"382 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139835421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Predicting factors of survival rates among alpha- and beta-thalassemia patients: a retrospective 10-year data analysis 甲型和乙型地中海贫血患者生存率的预测因素：10 年回顾性数据分析

Frontiers in hematology Pub Date : 2024-02-05 DOI: 10.3389/frhem.2024.1339026

Kunapa Iam-arunthai, T. Suwanban, Pravinwan Thungthong, Supat Chamnanchanunt, Suthat Fucharoen

{"title":"Predicting factors of survival rates among alpha- and beta-thalassemia patients: a retrospective 10-year data analysis","authors":"Kunapa Iam-arunthai, T. Suwanban, Pravinwan Thungthong, Supat Chamnanchanunt, Suthat Fucharoen","doi":"10.3389/frhem.2024.1339026","DOIUrl":"https://doi.org/10.3389/frhem.2024.1339026","url":null,"abstract":"Thalassemia is a genetic hemoglobinopathy in which a defective globin chain can cause transfusion-dependent anemia and other complications. As genotype interactions lead to variations in the clinical course among patients with thalassemia, clinical factors may help predict survival in the types of thalassemia complicated by gene interactions.This study aimed to determine the clinical factors associated with survival in patients with thalassemia. We retrospectively reviewed the medical records of patients with thalassemia older than 15 years between 2002 and 2020 that were available at the Rajavithi Hospital. Data on the clinical parameters, laboratory tests, treatments, and survival status were collected and analyzed.Of the 478 thalassemia patients included, 68.8% were women, and the mean age was 41 ± 17 years. The most common type of thalassemia was β-thalassemia (53.3%). Male sex, low body mass index, the thalassemia type, comorbidities, low hemoglobin level, high ferritin level, and regular blood transfusion were significantly associated with short-term survival. However, only the thalassemia type (β-thalassemia, p = 0.048) and the co-inheritance of the α- and β-thalassemia genotypes (p = 0.03) were independently associated with death. The overall survival rates among patients with α-thalassemia, β-thalassemia, and co-inheritance of the α- and β-thalassemia genotypes were 98.1%, 90.6%, and 75.0%, respectively. The death rate was 6.3%, and the most common cause of death was infection.The thalassemia genotype was a predictive factor of survival, and co-inheritance of the α- and β-thalassemia genotypes results in a shorter-term survival compared with other types, especially transfusion-dependent thalassemia. These results can be applied in clinical settings to predict and possibly extend the life expectancy of patients with thalassemia.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"14 25","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139803563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Predicting factors of survival rates among alpha- and beta-thalassemia patients: a retrospective 10-year data analysis 甲型和乙型地中海贫血患者生存率的预测因素：10 年回顾性数据分析

Frontiers in hematology Pub Date : 2024-02-05 DOI: 10.3389/frhem.2024.1339026

Kunapa Iam-arunthai, T. Suwanban, Pravinwan Thungthong, Supat Chamnanchanunt, Suthat Fucharoen

{"title":"Predicting factors of survival rates among alpha- and beta-thalassemia patients: a retrospective 10-year data analysis","authors":"Kunapa Iam-arunthai, T. Suwanban, Pravinwan Thungthong, Supat Chamnanchanunt, Suthat Fucharoen","doi":"10.3389/frhem.2024.1339026","DOIUrl":"https://doi.org/10.3389/frhem.2024.1339026","url":null,"abstract":"Thalassemia is a genetic hemoglobinopathy in which a defective globin chain can cause transfusion-dependent anemia and other complications. As genotype interactions lead to variations in the clinical course among patients with thalassemia, clinical factors may help predict survival in the types of thalassemia complicated by gene interactions.This study aimed to determine the clinical factors associated with survival in patients with thalassemia. We retrospectively reviewed the medical records of patients with thalassemia older than 15 years between 2002 and 2020 that were available at the Rajavithi Hospital. Data on the clinical parameters, laboratory tests, treatments, and survival status were collected and analyzed.Of the 478 thalassemia patients included, 68.8% were women, and the mean age was 41 ± 17 years. The most common type of thalassemia was β-thalassemia (53.3%). Male sex, low body mass index, the thalassemia type, comorbidities, low hemoglobin level, high ferritin level, and regular blood transfusion were significantly associated with short-term survival. However, only the thalassemia type (β-thalassemia, p = 0.048) and the co-inheritance of the α- and β-thalassemia genotypes (p = 0.03) were independently associated with death. The overall survival rates among patients with α-thalassemia, β-thalassemia, and co-inheritance of the α- and β-thalassemia genotypes were 98.1%, 90.6%, and 75.0%, respectively. The death rate was 6.3%, and the most common cause of death was infection.The thalassemia genotype was a predictive factor of survival, and co-inheritance of the α- and β-thalassemia genotypes results in a shorter-term survival compared with other types, especially transfusion-dependent thalassemia. These results can be applied in clinical settings to predict and possibly extend the life expectancy of patients with thalassemia.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"14 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139863397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How artificial intelligence revolutionizes the world of multiple myeloma 人工智能如何彻底改变多发性骨髓瘤的世界

Frontiers in hematology Pub Date : 2024-02-02 DOI: 10.3389/frhem.2024.1331109

Martha Romero, A. Mosquera Orgueira, Mateo Mejia Saldarriaga

{"title":"How artificial intelligence revolutionizes the world of multiple myeloma","authors":"Martha Romero, A. Mosquera Orgueira, Mateo Mejia Saldarriaga","doi":"10.3389/frhem.2024.1331109","DOIUrl":"https://doi.org/10.3389/frhem.2024.1331109","url":null,"abstract":"Multiple myeloma is the second most frequent hematologic malignancy worldwide with high morbidity and mortality. Although it is considered an incurable disease, the enhanced understanding of this neoplasm has led to new treatments, which have improved patients’ life expectancy. Large amounts of data have been generated through different studies in the settings of clinical trials, prospective registries, and real-world cohorts, which have incorporated laboratory tests, flow cytometry, molecular markers, cytogenetics, diagnostic images, and therapy into routine clinical practice. In this review, we described how these data can be processed and analyzed using different models of artificial intelligence, aiming to improve accuracy and translate into clinical benefit, allow a substantial improvement in early diagnosis and response evaluation, speed up analyses, reduce labor-intensive process prone to operator bias, and evaluate a greater number of parameters that provide more precise information. Furthermore, we identified how artificial intelligence has allowed the development of integrated models that predict response to therapy and the probability of achieving undetectable measurable residual disease, progression-free survival, and overall survival leading to better clinical decisions, with the potential to inform on personalized therapy, which could improve patients’ outcomes. Overall, artificial intelligence has the potential to revolutionize multiple myeloma care, being necessary to validate in prospective clinical cohorts and develop models to incorporate into routine daily clinical practice.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"9 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139683340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug exporter expression correlates with group 3 innate lymphoid cell resistance to immunosuppressive agents 药物输出者的表达与第3组先天淋巴样细胞对免疫抑制剂的耐药性相关

Frontiers in hematology Pub Date : 2023-08-25 DOI: 10.3389/frhem.2023.1144418

Said Z. Omar, N. Haverkate, Vera van Hoeven, B. Blom, M. Hazenberg

{"title":"Drug exporter expression correlates with group 3 innate lymphoid cell resistance to immunosuppressive agents","authors":"Said Z. Omar, N. Haverkate, Vera van Hoeven, B. Blom, M. Hazenberg","doi":"10.3389/frhem.2023.1144418","DOIUrl":"https://doi.org/10.3389/frhem.2023.1144418","url":null,"abstract":"Allogeneic hematopoietic cell transplantation (HCT) is often complicated by graft versus host disease (GvHD), an alloreactive immune response triggered by tissue damage. Interleukin (IL)-22 producing type 3 innate lymphoid cells (ILC3) protect epithelial tissues against chemo(radio)therapy-induced damage, suppress alloreactive T cells and mitigate acute GvHD symptoms after allogeneic HCT. Relatively high numbers of ILC before and after allogeneic HCT has been associated with significantly reduced tissue damage and less acute GvHD. While most transplantation conditioning and GvHD prophylaxis regimens are aimed at eliminating host and alloreactive donor lymphocytes, the effect of these regimens on ILC remain elusive. Here, we studied the effect of conditioning chemotherapy and immunosuppressive agents on the survival, proliferation, activation and function of human ILC3 in vitro. Tonsil-derived ILC3 were activated and incubated with agents commonly used to prevent and treat GvHD. While fludarabine, rapamycin, mycophenolic acid and prednisolone suppressed ILC3 to a similar degree as T cells, the effect of other agents, including cyclosporine A, methotrexate, imatinib, ibrutinib and ruxolitinib, was milder on ILC3 than on T cells. ILC3 are less sensitive to immunosuppressants potentially because of their expression of functionally active ATP Binding Cassette Subfamily B Member 1 (ABCB1) drug exporter proteins. This suggests less intracellular accumulation of immunosuppressive agents, which renders ILC3 resistant to these compounds. The present findings may help to develop strategies to simultaneously maintain the tissue protective properties of ILC3 and at the same time suppress alloreactive lymphocytes, which is important in the prevention and treatment of acute GvHD.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133532885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The research for various genotypes and phenotypes related to rare -90 (C>T) β-thalassemia mutation in Ganzhou city, Southern China 赣州市罕见的-90 (C>T) β-地中海贫血突变相关基因型和表型研究

Frontiers in hematology Pub Date : 2023-08-14 DOI: 10.3389/frhem.2023.1234726

Hui-juan Zhang, Xiao-Mei Hu, De-Dong Liu

{"title":"The research for various genotypes and phenotypes related to rare -90 (C>T) β-thalassemia mutation in Ganzhou city, Southern China","authors":"Hui-juan Zhang, Xiao-Mei Hu, De-Dong Liu","doi":"10.3389/frhem.2023.1234726","DOIUrl":"https://doi.org/10.3389/frhem.2023.1234726","url":null,"abstract":"Thalassemia is a heterogeneous group of genetic disorders affecting the hemoglobin genes leading to decrease synthesis of globin chains of hemoglobin and resulting in ineffective erythropoiesis. It usually contains α- and β-thalassemia, most of common mutation types of which can be detected. However, it’s inclined to miss rare thalassemia mutation types. Here, we analyzed the molecular and hematological characteristics of seven cases with rare β-thalassemia -90 (C>T) (HBB: c.-140 C>T) mutation. Five of them carried β-90 (C>T) heterozygous mutation with a β+ thalassemia trait. One case was αSEA/β-90 genotype with decreasing MCV and MCH obviously, and the other was a β+/β0 intermediate thalassemia patient with β-90/βCD17 genotype, presenting with moderate anemia. A pedigree of one case was analyzed subsequently. It was found that the proband’s maternal grandfather and mother were carriers of α3.7/β-90 double heterozygous thalassemia, who presented that MCV and MCH were decreased normally or slightly, and HbA2 was increased. The proband and his aunt were β-90 (C>T) carriers. It’s necessary to point that the MCV and MCH were much higher in carrier of α3.7/β-90 genotype compared with either αSEA/β-90 genotype or β-90 heterozygous mutation. In this study, we explore the genotypes and phenotypes of four diverse β-90、αSEA/β-90、α3.7/β-90、β-90/βCD17 thalassemia mutations, which enriches the gene profile of β-thalassemia mutation in Chinese population.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115426536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The link between immune thrombocytopenia and the cytokine profile: a bridge to new therapeutical targets 免疫性血小板减少症与细胞因子谱之间的联系:通往新治疗靶点的桥梁

Frontiers in hematology Pub Date : 2023-08-10 DOI: 10.3389/frhem.2023.1191178

M. Andreescu

{"title":"The link between immune thrombocytopenia and the cytokine profile: a bridge to new therapeutical targets","authors":"M. Andreescu","doi":"10.3389/frhem.2023.1191178","DOIUrl":"https://doi.org/10.3389/frhem.2023.1191178","url":null,"abstract":"Immune thrombocytopenia (ITP) manifests as depleted platelet reserves, primarily due to the immune-mediated destruction of platelets. The pathogenesis of ITP is complex and involves dysregulation of the immune system. This review aimed to summarize the current knowledge of the cytokine profile in ITP and its potential implications for diagnosis, treatment, and prognosis. Several studies have reported that ITP patients have an altered cytokine profile from that of healthy individuals. Specifically, there is evidence of an imbalance of pro-inflammatory (interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ) and anti-inflammatory cytokines (IL-10, TGF-β). The cytokine profile in ITP appears to be heterogeneous, with different patterns observed in different subsets of patients. For example, some studies have reported a Th1-type cytokine profile, characterized by elevated levels of IFN-γ and TNF-α, while others have reported a Th2-type cytokine profile, characterized by elevated levels of IL-4 and IL-10. There is also evidence of a shift from a Th1 to a Th2 cytokine profile in some patients over time. The cytokine profile in ITP may have important implications for diagnosis, treatment, and prognosis. Targeting specific cytokines or cytokine pathways may also represent a promising therapeutic approach for ITP. Further studies are needed to better understand the heterogeneity of the cytokine profile in ITP and its potential implications for clinical management.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114785290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Knowledge, attitude, and practice of physicians regarding pain management in patients with Sickle cell disease 镰状细胞病患者疼痛管理的医生的知识、态度和实践

Frontiers in hematology Pub Date : 2023-08-04 DOI: 10.3389/frhem.2023.1214902

Abdellatif Ismail, Ali Aqel, Ma’in Abumuhfouz, Mohamad Safieh, M. Arabyat, M. Ibrahim, Kalpana Singh, M. Yassin

{"title":"Knowledge, attitude, and practice of physicians regarding pain management in patients with Sickle cell disease","authors":"Abdellatif Ismail, Ali Aqel, Ma’in Abumuhfouz, Mohamad Safieh, M. Arabyat, M. Ibrahim, Kalpana Singh, M. Yassin","doi":"10.3389/frhem.2023.1214902","DOIUrl":"https://doi.org/10.3389/frhem.2023.1214902","url":null,"abstract":"Sickle cell disease (SCD) is a hemoglobin disorder inherited in an autosomal recessive pattern. Pain from vaso-occlusive crises (VOCs) is the most common symptom experienced by patients with SCD; thus, pain management constitutes a significant role in this patient population. We hypothesized that physicians with less favorable attitudes toward SCD patients are less likely to follow pain management guidelines. In this cross-sectional convenience sample survey, we aimed to assess the adherence of physicians in our institute to guidelines for the management of SCD pain crises and study the factors that are associated with non-adherence to these guidelines. Most surveyed physicians were early in their career and were found to adhere to the recommendations of using opioids and NSAIDs as a first-line therapy and avoiding using meperidine. On the other hand, some analgesic practices deviated from the recommendations, including less frequent assessment and reassessment of pain and response to pain medications and less frequent use of opioid patient-controlled analgesia (PCA). It is noteworthy that the frequency and severity of untreated pain in patients with SCD are associated with higher mortality, thus appropriate comprehensive care for such a vulnerable population should be prioritized and optimized. Although we did not find an association between the providers’ attitudes toward SCD patients and their pain management practices, improving these attitudes will promote the provider–patient relationship and its therapeutic outcomes. We conclude that the physicians taking care of SCD patients in our institute adhere to some of the guidelines in the field more than others. We also conclude that they have negative attitudes toward SCD patients; nevertheless, these did not affect their pain management practices.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"73 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132479623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A systematic review investigating advances in gene therapy for Fanconi anemia over the last three decades 系统回顾了过去三十年来范可尼贫血基因治疗的进展

Frontiers in hematology Pub Date : 2023-08-03 DOI: 10.3389/frhem.2023.1216596

Lorna M. McLeman, A. Glaser, R. Conyers, A. Deans

{"title":"A systematic review investigating advances in gene therapy for Fanconi anemia over the last three decades","authors":"Lorna M. McLeman, A. Glaser, R. Conyers, A. Deans","doi":"10.3389/frhem.2023.1216596","DOIUrl":"https://doi.org/10.3389/frhem.2023.1216596","url":null,"abstract":"Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome, characterized by cellular DNA repair deficiency, developmental defects, and a 700-fold increased risk of developing cancer. A bone marrow transplant is the only treatment option for the hematological manifestations of FA, but it can have serious complications. Gene therapy, on the other hand, offers a promising alternative, using cells from the patient that have been corrected ex vivo. However, due to the complexity of cells with a compromised DNA repair pathway, it has been difficult to achieve success in treating FA with gene therapy, despite advancements in the treatment of other blood disorders. This review summarizes all published human trials to date, including a recent study that reported success in treating four pediatric patients with gene therapy, and its interim Phase II study that has successfully treated six further patients. We discuss the key advances, such as improvements in viral vectors, shorter ex vivo transduction protocols, and the use of hypoxia and/or media additives such as N-acetylcysteine or etanercept. We also discuss the potential use of mobilizing agents such as granulocyte-colony stimulating factor (G-CSF) and plerixafor. The data from human trials are systematically reviewed and advances in murine and in vitro studies are discussed.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127728364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Abatacept and T-cell costimulation blockade—shifting the paradigm in the prevention of graft-versus-host disease abataccept和t细胞共刺激阻断转移在预防移植物抗宿主病中的范例

Frontiers in hematology Pub Date : 2023-08-03 DOI: 10.3389/frhem.2023.1243247

S. Chakrabarti, S. Jaiswal

{"title":"Abatacept and T-cell costimulation blockade—shifting the paradigm in the prevention of graft-versus-host disease","authors":"S. Chakrabarti, S. Jaiswal","doi":"10.3389/frhem.2023.1243247","DOIUrl":"https://doi.org/10.3389/frhem.2023.1243247","url":null,"abstract":"Despite advances in transplantation techniques and immunosuppressive therapies, graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality, necessitating the use of innovative strategies for its prevention. T-cell activation plays a crucial role in the pathogenesis of GVHD, and T-cell costimulation blockade (COSBL) has emerged as a promising approach to prevent this devastating condition. This review aims to explore the concept of COSBL and its potential as a paradigm-shifting strategy in the prevention of GVHD, in the context of the existing modalities for the prevention of GVHD and the preclinical and clinical studies on COSBL. The unique property of abatacept (CTLA4Ig) is not just limited to dampening T-cell activation. The salutary effect of abatacept on natural killer (NK) cells and Tregs alike provides a unique opportunity to dissociate T-cell-mediated GVHD from NK cell-mediated graft-versus-leukemia. Further research is warranted to explore other modalities of COSBL, determine the optimal dosing and combinations for COSBL, and identify predictive biomarkers for patient stratification, ultimately paving the way for improved outcomes in hematopoietic cell transplantation recipients.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"94 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114579932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0