Therapeutic Advances in Hematology最新文献

{"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}

{"title":"Avatrombopag for the salvage treatment of platelet transfusion refractoriness.","authors":"Yuehong Qin, Yu Wang, Yujiao Zhang, Yingying Jiao, Jieyu Ye","doi":"10.1177/20406207241237606","DOIUrl":"10.1177/20406207241237606","url":null,"abstract":"<p><strong>Background: </strong>Platelet transfusion refractoriness (PTR) is a life-threatening and intractable condition in hematological patients. Thrombopoietin receptor agonists such as avatrombopag promote platelet production and modulate immune intolerance. However, its application in PTR has not been extensively studied.</p><p><strong>Objectives: </strong>We aimed to compare the platelet response (PR) as well as bleeding events and mortality rate between the best available therapies (BATs) and avatrombopag (Ava) treatments in refractory PTR patients.</p><p><strong>Design: </strong>A total of 71 refractory PTR patients were enrolled at Nanfang Hospital. Intravenous immunoglobulin, steroids, and human leucocyte antigen-matched platelet transfusions were administered to 30 patients in the BATs group. The Ava group included 41 patients.</p><p><strong>Methods: </strong>Data of refractory PTR patients were retrospectively collected. The primary endpoint was PR (defined as an increase of platelet count to ⩾50 × 10⁹/L without platelet transfusion support for 7 consecutive days). Secondary endpoints included platelet-transfusion independence rate, cumulative platelet transfusion units, World Health Organization bleeding grades, adverse events, overall survival (OS), and bleeding event-free survival (EFS).</p><p><strong>Results: </strong>There were 75.6% and 13.3% refractory PTR patients who reached PR within 3 months in Ava and BATs groups. The median platelet counts were significantly higher in Ava group from day 7. Platelet-transfusion independence rate in Ava was higher than BATs group. The median cumulative platelet transfusion unit in Ava was lower than that of BATs group. The OS and bleeding events-free EFS rate of Ava group improved within 3 months as compared to BATs group. Cox proportional hazards regression analysis revealed that Ava therapy was a protective factor for the OS and EFS. No primary disease progression or termination of avatrombopag was observed due to intolerability.</p><p><strong>Conclusion: </strong>Our study suggests that avatrombopag is an effective and safe treatment option for refractory PTR patients.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241237606"},"PeriodicalIF":3.4,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120636","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":"Progress and prospect of ASCT combined with CAR-T therapy in the treatment of multiple myeloma.","authors":"Shihui Yuan, Ying Chen, Huasheng Liu","doi":"10.1177/20406207241237594","DOIUrl":"10.1177/20406207241237594","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a hematological cancer characterized by abnormal proliferation of plasma cells in bone marrow. In recent years, autologous stem cell transplantation (ASCT) has become the cornerstone of MM treatment. At the same time, immunotherapy, such as monoclonal antibody therapy and chimeric antigen receptor T cell (CAR-T) has also emerged, in which CAR-T is the most attractive focus. ASCT and its myeloablative preconditioning will turn its immune microenvironment into an inhibited state, which may provide an opportunity for the expansion of CAR-T cells so as to further clear the residual lesions after ASCT and reduce the recurrence rate after ASCT. Meanwhile, the infusion of CAR-T cells can accelerate the cellular immune reconstruction after ASCT of myeloma, thereby improving the antitumor effect. In order to explore the clinic value, this article reviews the progress and prospect of ASCT combined with CAR-T therapy in the treatment of MM.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241237594"},"PeriodicalIF":3.4,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120637","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 phase I trial of pevonedistat in combination with ruxolitinib for the treatment of myelofibrosis.","authors":"Tim Kong, Nicole Gaudin, Karyn Gordon, Maggie J Cox, Amy W Zhou, Stephen T Oh","doi":"10.1177/20406207241237607","DOIUrl":"10.1177/20406207241237607","url":null,"abstract":"<p><p>Janus kinase 2 (JAK2) inhibitors such as ruxolitinib have become standard-of-care therapy for patients with myeloproliferative neoplasms (MPNs); however, activation of alternate oncogenic pathways including nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) has limited durable response as single-agent therapy. With the rationale of targeting both pathways, we conducted a phase I dose escalation trial of pevonedistat in combination with ruxolitinib for the treatment of patients with myelofibrosis (NCT03386214). The primary objective was to assess the safety and tolerability of combination therapy with additional objectives of treatment efficacy and alterations of biomarkers. There were no dose-limiting toxicities observed with most adverse events being limited to grades 1/2. In secondary measures, anemia response was observed in two patients. Pro-inflammatory cytokines and iron parameters were longitudinally assessed, which revealed suppression of interleukin-6 and interferon-gamma in a dose-dependent manner across a subset of patients. These results suggest that combination therapy targeting both JAK2 and NFκB may hold clinical merit for MPN patients.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241237607"},"PeriodicalIF":3.4,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120635","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":"An occurrence of eosinophilic folliculitis and alopecia associated with a sustained complete response to mogamulizumab in Sézary syndrome: a case report","authors":"Jean-Matthieu L’Orphelin","doi":"10.1177/20406207241235777","DOIUrl":"https://doi.org/10.1177/20406207241235777","url":null,"abstract":"Mogamulizumab is a monoclonal antibody that binds to C–C chemokine receptor 4 (CCR4), initiating antibody-dependent cellular cytotoxicity. CCR4 is highly expressed in the cutaneous T-cell lymphoma subtypes mycosis fungoides and Sézary syndrome (SS), and mogamulizumab has been shown to be effective in patients with these conditions who were refractory to at least one prior systemic treatment. One of the more common adverse events encountered with mogamulizumab is rash, which may mimic disease progression and lead to premature discontinuation. Moreover, there has been some evidence to suggest that mogamulizumab-associated rash (MAR) is associated with improved outcomes in some patients, particularly those with SS. This report presents the case of a 72-year-old woman with SS, which manifested with macular and papular lesions and abnormal blood cytometry, who was treated with mogamulizumab after failure of bexarotene and photopheresis combination therapy. She achieved a complete response (CR), but experienced lymphopenia associated with histologically proven eosinophilic folliculitis (EF) of the scalp and alopecia. The EF responded well to initial topical corticosteroids, defined by regression of erythema and pustular involvement and reduction in pruritus-like symptoms, but without hair regrowth. Mogamulizumab was withdrawn after 32 cycles, but CR was maintained. To date, EF persists in the form of diffuse erythema without pustules or pruritus. A link between cluster of differentiation 4 lymphopenia and EF has previously been established; therefore, EF should be considered in patients who develop rash and lymphopenia while receiving treatment with mogamulizumab. MAR has been associated with clinical response to mogamulizumab, and this case report adds to the evidence that EF may also be associated with sustained clinical response following treatment cessation. However, regular monitoring is required to prevent a relapse of SS. Prospective studies are needed to confirm whether such an association between EF and CR following mogamulizumab exists.","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"24 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140056493","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":"Interferons in the treatment of myeloproliferative neoplasms.","authors":"Pankit Vachhani, John Mascarenhas, Prithviraj Bose, Gabriela Hobbs, Abdulraheem Yacoub, Jeanne M Palmer, Aaron T Gerds, Lucia Masarova, Andrew T Kuykendall, Raajit K Rampal, Ruben Mesa, Srdan Verstovsek","doi":"10.1177/20406207241229588","DOIUrl":"10.1177/20406207241229588","url":null,"abstract":"<p><p>Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule. In the current therapeutic landscape, pegylated interferons are recommended for use in the treatment of polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We review recent efficacy, molecular response, and safety data for the two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi). The practical management of interferon-based therapies is discussed, along with our opinions on whether to and how to switch from hydroxyurea to one of these therapies. Key topics and questions related to use of interferons, such as their safety and tolerability, the significance of variant allele frequency, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241229588"},"PeriodicalIF":3.4,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913474","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}