Therapeutic Advances in Hematology最新文献

{"title":"Updates of primary central nervous system lymphoma.","authors":"Jiaying Wu, Delian Zhou, Xiaojian Zhu, Yicheng Zhang, Yi Xiao","doi":"10.1177/20406207241259010","DOIUrl":"10.1177/20406207241259010","url":null,"abstract":"<p><p>Lymphoma occurring in the central nervous system is considered primary central nervous system lymphoma (PCNSL), usually without systematic lesions. Over the last few decades, a deep understanding of PCNSL has been lacking due to the low incidence rate, and the overall survival and progression-free survival of patients with PCNSL are lower than those with other types of non-Hodgkin lymphoma. Recently, there have been several advancements in research on PCNSL. Advances in diagnosis of the disease are primarily reflected in the promising diagnostic efficiency of novel biomarkers. Pathogenesis mainly involves abnormal activation of nuclear factor kappa-B signaling pathways, copy number variations, and DNA methylation. Novel therapies such as Bruton's tyrosine kinase inhibitors, immunomodulatory drugs, immune checkpoint inhibitors, and phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors are being evaluated as possible treatment options for PCNSL, especially for relapsed/refractory (R/R) cases. Several clinical trials also indicated the promising feasibility and efficacy of chimeric antigen receptor T-cell therapy for selected R/R PCNSL patients. This review focuses on discussing recent updates, including the diagnosis, pathogenesis, and novel therapy of PCNSL.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241259010"},"PeriodicalIF":3.4,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11177745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic literature review of 74 Chinese blastic plasmacytoid dendritic cell neoplasm patients.","authors":"Chen Gong, Ying Liu, Mingzhi Zhang","doi":"10.1177/20406207241251602","DOIUrl":"10.1177/20406207241251602","url":null,"abstract":"<p><strong>Background: </strong>Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological cancer. Due to its low incidence, researchers struggle to gather sufficient prospective data to inform clinical treatment.</p><p><strong>Objectives: </strong>We sought to summarize the clinical characteristics and current treatment methods of BPDCN and provide more specific guidance on treatment options.</p><p><strong>Design: </strong>A systematic literature review using data from 74 Chinese BPDCN patients.</p><p><strong>Date resources and methods: </strong>We retrospectively analyzed the clinical manifestations, treatment response, survival outcomes, and prognostic factors of six BPDCN patients treated at the First Affiliated Hospital of Zhengzhou University and 68 patients described in 28 articles published in the China Knowledge Network database since 2019.</p><p><strong>Results: </strong>In Chinese patients, the disease occurred with a male-to-female ratio of 2.52 and a median age of onset of 50 years in adults and 10 years in pediatric patients. Immunohistochemical analysis revealed distinctive immune phenotypes of BPDCN cells, characterized by high expression levels of CD4, CD56, CD123, and HLA-DR, while showing minimal to no expression of myeloperoxidase (MPO), CD20, and CD79a. There was no significant difference in the initial complete remission (CR) rate, relapse rate, and the overall survival (OS) time of patients receiving acute myeloid leukemia-like, acute lymphocytic leukemia-like, or non-Hodgkin's lymphoma-like chemotherapy regimens. Univariate analysis identified CD3 expression, male gender, and central nervous system infiltration as hazardous factors. In multivariate analysis, age proved to be an independent prognostic indicator, indicating better prognosis and longer OS time in younger patients. Notably, hematopoietic stem cell transplantation (HSCT) emerged as a significant factor in improving the survival outcomes for individuals diagnosed with BPDCN. However, further investigation is needed to explore the role of HSCT and the best timing for its implementation in pediatric BPDCN patients.</p><p><strong>Conclusion: </strong>Administering HSCT during the initial CR state following inductive chemotherapy might extend the OS and improve the prognosis of patients with BPDCN.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241251602"},"PeriodicalIF":3.4,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11145996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intensive chemotherapy with dual induction and ALL-like consolidation for childhood acute myeloid leukemia: a respective report from multiple centers in China","authors":"Jia-Nan Li, Yi-Jun Chen, Zhong Fan, Qiao-Ru Li, Liu-Hua Liao, Zhi-Yong Ke, Yu Li, Li-Na Wang, Cui-Yun Yang, Xue-Qun Luo, Yan-Lai Tang, Xiao-Li Zhang, Li-Bin Huang","doi":"10.1177/20406207241256894","DOIUrl":"https://doi.org/10.1177/20406207241256894","url":null,"abstract":"Background:Pediatric acute myeloid leukemia (AML) has poor prognosis and high rate of relapse and mortality, and exploration of new treatment options is still critically needed.Objectives:To summarize the outcome of our new treatment strategies for pediatric AML, which is characterized by dual induction and acute lymphoblastic leukemia (ALL) elements consolidation.Design:Retrospective, single-arm study.Methods:From July 2012 to December 2019, an intensive chemotherapy protocol was used for newly diagnosed children with AML, which contains dual induction, three courses of consolidations based on high-dose cytarabine, and two courses of consolidations composed of high-dose methotrexate, vincristine, asparaginase, and mercaptopurine (ALL-like elements). Blasts were monitored by bone marrow smears at intervals, and two lumbar punctures were performed during chemotherapy. We retrospectively analyzed the efficacy and safety of this study. The last follow-up was on 26 May 2023.Results:A total of 70 pediatric AMLs were included. The median age at diagnosis was 6.7 (0.5–16.0) years. The median initial WBC count was 23.74 × 10<jats:sup>9</jats:sup>/L, 11 of whom ⩾100 × 10<jats:sup>9</jats:sup>/L. After dual induction, there were 62 cases of complete remission (CR), 5 cases of partial remission, and 3 cases of nonremission. The CR rate was 88.57%. The median follow-up time was 5.8 (0.2–9.4) years, the 5-year overall survival was 78.2% ± 5%, the event-free survival (EFS) was 71.2% ± 5.6%, and the cumulative recurrence rate was 27.75%. The 5-year EFS of patients with initial WBC &lt; 100 × 10<jats:sup>9</jats:sup>/L ( n = 59) and ⩾100 × 10<jats:sup>9</jats:sup>/L ( n = 11) were 76.4% ± 5.7% and 45.5% ± 15% ( p = 0.013), respectively. A total of 650 hospital infections occurred. The main causes of infection were respiratory tract infection (26.92%), septicemia (18.46%), stomatitis (11.85%), and skin and soft-tissue infection (10.46%).Conclusion:This intensive treatment protocol with dual induction and ALL-like elements is effective and safe for childhood AML. Initial WBC ⩾ 100 × 10<jats:sup>9</jats:sup>/L was the only independent risk factor in this cohort.Trial registration:It is a retrospective study, and no registration on ClinicalTrials.gov.","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"2010 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modified BEAM as a conditioning regimen for mantle cell lymphoma patients undergoing autologous hematopoietic stem cell transplantation","authors":"Piero Galieni, Sadia Falcioni, Emanuela Troiani, Paola Picardi, Catia Bigazzi, Denise Maravalle, Federica De Giorgi, Roberta Taborro, Stefano Angelini","doi":"10.1177/20406207241251541","DOIUrl":"https://doi.org/10.1177/20406207241251541","url":null,"abstract":"","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"2 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141061329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a nomogram to predict the risk of secondary failure of platelet recovery in patients with β-thalassemia major after hematopoietic stem cell transplantation: a retrospective study.","authors":"Yanni Xie, Gaohui Yang, Lin Pan, Zhaoping Gan, Yumei Huang, Yongrong Lai, Rongrong Liu","doi":"10.1177/20406207241245190","DOIUrl":"10.1177/20406207241245190","url":null,"abstract":"<p><strong>Background: </strong>Secondary failure of platelet recovery (SFPR) is a common complication that influences survival and quality of life of patients with β-thalassemia major (β-TM) after hematopoietic stem cell transplantation (HSCT).</p><p><strong>Objectives: </strong>A model to predict the risk of SFPR in β-TM patients after HSCT was developed.</p><p><strong>Design: </strong>A retrospective study was used to develop the prediction model.</p><p><strong>Methods: </strong>The clinical data for 218 β-TM patients who received HSCT comprised the training set, and those for another 89 patients represented the validation set. The least absolute shrinkage and selection operator regression algorithm was used to identify the critical clinical factors with nonzero coefficients for constructing the nomogram. Calibration curve, C-index, and receiver operating characteristic curve assessments and decision curve analysis (DCA) were used to evaluate the calibration, discrimination, accuracy, and clinical usefulness of the nomogram. Internal and external validation were used to test and verify the predictive model.</p><p><strong>Results: </strong>The nomogram based on pretransplant serum ferritin, hepatomegaly, mycophenolate mofetil use, and posttransplant serum albumin could be conveniently used to predict the SFPR risk of thalassemia patients after HSCT. The calibration curve of the nomogram revealed good concordance between the training and validation sets. The nomogram showed good discrimination with a C-index of 0.780 (95% CI: 70.3-85.7) and 0.868 (95% CI: 78.5-95.1) and AUCs of 0.780 and 0.868 in the training and validation sets, respectively. A high C-index value of 0.766 was reached in the interval validation assessment. DCA confirmed that the nomogram was clinically useful when intervention was decided at the possibility threshold ranging from 3% to 83%.</p><p><strong>Conclusion: </strong>We constructed a nomogram model to predict the risk of SFPR in patients with β-TM after HSCT. The nomogram has a good predictive ability and may be used by clinicians to identify SFPR patients early and recommend effective preventive measures.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241245190"},"PeriodicalIF":3.4,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11084996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simoctocog alfa (Nuwiq^®) in children: early steps in life's journey for people with severe hemophilia A.","authors":"Anna Klukowska, Robert F Sidonio, Guy Young, Maria Elisa Mancuso, María Teresa Álvarez-Román, Neha Bhatnagar, Martina Jansen, Sigurd Knaub","doi":"10.1177/20406207241245511","DOIUrl":"10.1177/20406207241245511","url":null,"abstract":"<p><p>People with severe hemophilia A usually experience their first bleed early in life. In children with severe hemophilia A, primary prophylaxis is recommended to prevent recurrent and potentially life-threatening bleeds that significantly impact day-to-day life. Factor VIII (FVIII) prophylaxis is well-established in children and has been shown to reduce the development of hemophilic arthropathy. However, a major challenge of FVIII therapy is the development of neutralizing anti-FVIII antibodies (FVIII inhibitors). Simoctocog alfa (Nuwiq^®) is a human cell line-derived recombinant FVIII (rFVIII) whose immunogenicity, efficacy, and safety have been studied in 167 children with severe hemophilia A across two prospective clinical trials and their long-term extensions. In 105 previously untreated children, the inhibitor rate of 16.2% for high-titer inhibitors (26.7% for all inhibitors) was lower than published rates for hamster cell line-derived rFVIII products. There was no inhibitor development in previously untreated children with non-null <i>F8</i> mutations and in previously treated children. In a case series of 10 inhibitor patients, 8 (80%) underwent successful immune tolerance induction with simoctocog alfa with a median time to undetectable inhibitor of 3.5 months. In an analysis of 96 children who enrolled in the extension studies and received long-term simoctocog alfa prophylaxis for up to 5 years, median spontaneous, joint, and total annualized bleeding rates were 0.3, 0.4, and 1.8, respectively. No thromboembolisms were reported in any of the 167 children, and there were no treatment-related deaths. Optimal care of children should consider several factors, including minimization of inhibitor development risk, maintaining tolerance to FVIII, highly effective bleed prevention and treatment, safety, and impact on long-term outcomes such as bone and joint health. In this context we review the pediatric clinical data and ongoing studies with simoctocog alfa.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241245511"},"PeriodicalIF":3.4,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of multiple myeloma: What is the impact on T-cell function?","authors":"Chenggong Li, Xindi Wang, Jia Xu, Jiachen Liu, Heng Mei","doi":"10.1177/20406207241245194","DOIUrl":"10.1177/20406207241245194","url":null,"abstract":"<p><p>Treatment of multiple myeloma (MM) has evolved remarkably over the past few decades. Autologous stem cell transplantation, as well as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, has substantially improved the prognosis of patients with MM. Novel therapies, including chimeric antigen receptor-T cells, bispecific T-cell engagers, antibody-drug conjugates, histone deacetylase inhibitors, and nuclear export inhibitors, have provided more options. However, MM remains incurable. T cells are the principal weapons of antitumor immunity, but T cells display a broad spectrum of dysfunctional states during MM. The promising clinical results of T-cell-directed immunotherapies emphasize the significance of enhancing T-cell function in antimyeloma treatment. This review summarizes the potential effects of these antimyeloma agents on T-cell function and discusses possible optimized strategies for MM management by boosting T-cell immunity.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241245194"},"PeriodicalIF":3.4,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11078088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved survival outcomes with anakinra over etoposide-based therapies for the management of adults with hemophagocytic lymphohistiocytosis: a retrospective multicenter research network study","authors":"Benjamin J. Lee","doi":"10.1177/20406207241245517","DOIUrl":"https://doi.org/10.1177/20406207241245517","url":null,"abstract":"Background:Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening, hyperinflammatory syndrome for which etoposide-based regimens have historically been the standard of care. Recent reports have described positive outcomes with the utilization of ruxolitinib or anakinra although these studies are often limited to small samples.Objectives:We aimed to compare the efficacy of ruxolitinib, anakinra, and etoposide-based therapies for the management of HLH in adult patients.Design:We performed a population-based, multicenter, retrospective cohort study utilizing the TriNetX Networks database.Methods:Adult patients (⩾18 years) diagnosed with HLH who received first-line treatment with ruxolitinib, anakinra, or etoposide between 2008 and 2023 were analyzed. The primary endpoint was overall survival (OS) at 1 year. A 1:1 propensity-score matching analysis was utilized.Results:Anakinra ( p = 0.020) but not ruxolitinib ( p = 0.19) resulted in a significantly higher 1-year OS when compared with etoposide-based therapies.Conclusions:Anakinra is effective for the management of adult patients with HLH.","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"40 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in minimal residual disease detection: a practical approach using single-cell droplet PCR for comprehensive monitoring in hematological malignancy","authors":"Satoshi Uchiyama, Kentaro Fukushima, Seiichiro Katagiri, Junichi Tsuchiya, Tomohiro Kubo, SungGi Chi, Yosuke Minami","doi":"10.1177/20406207241245510","DOIUrl":"https://doi.org/10.1177/20406207241245510","url":null,"abstract":"The identification of chromosomal abnormalities accompanied by copy number alterations is important for understanding tumor characteristics. Testing methodologies for copy number abnormality have limited sensitivity, resulting in their use only for the sample provided at the time of diagnosis or recurrence of malignancy, but not for the monitoring of minimal residual disease (MRD) during and after therapy. We developped the “DimShift” technology which enable to measure the copy number of target gene/chromosome in each cell, which is given by the single cell droplet PCR. Qualitative result of DimShift given by peripheral blood was perfectly concordant with that of bone marrow. These findings and performances are promising to be the new methodology for MRD detection in malignant diseases utilizing bone marrow as well as peripheral blood.","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"24 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140572964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research advances on short-chain fatty acids in gastrointestinal acute graft-versus-host disease","authors":"Xinping Song, Jing Lao, Lulu Wang, Sixi Liu","doi":"10.1177/20406207241237602","DOIUrl":"https://doi.org/10.1177/20406207241237602","url":null,"abstract":"Gastrointestinal acute graft- versus-host disease (GI-aGVHD) is a severe early complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). It has been shown that the intestinal microbiota plays a critical role in this process. As metabolites of the intestinal microbiota, short-chain fatty acids (SCFAs) are vital for maintaining the host-microbiota symbiotic equilibrium. This article provides an overview of the protective effect of SCFAs in the gastrointestinal tract, emphasizes their association with GI-aGVHD, and explores relevant research progress in prevention and treatment research.","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"18 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140323988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}