Therapeutic Advances in Hematology最新文献

{"title":"Non-invasive prenatal testing for fetal Ss, Kidd, and CTL2 blood group prediction by multiplex digital droplet PCR.","authors":"Yufeng Wang,&nbsp;Xiaoyue Chu,&nbsp;Xihui Chen,&nbsp;Anan Yin,&nbsp;Yan Yao,&nbsp;Li Wang,&nbsp;Hua Xu,&nbsp;Fangfang Liu,&nbsp;Kun Chen,&nbsp;Yuanming Wu","doi":"10.1177/20406207231179334","DOIUrl":"https://doi.org/10.1177/20406207231179334","url":null,"abstract":"<p><strong>Background: </strong>Some blood groups, such as S and s blood groups in the MNS blood group system, and Kidd and CTL2 blood group systems, can cause severe fetal and newborn alloimmune disorders. Non-invasive prenatal testing (NIPT) to predict fetal blood groups and knowledge of local blood group gene frequency are both important for pregnancy management decisions. Droplet digital PCR (ddPCR) has high specificity and sensitivity in detecting fetal single nucleotide variation.</p><p><strong>Objectives: </strong>The objective is to predict fetal Ss, Kidd, and CTL2 blood groups using multiplex ddPCR. The gene frequencies of three blood groups were detected by ddPCR in northwest China.</p><p><strong>Design: </strong>This is a prospective study.</p><p><strong>Methods: </strong>Cell-free fetal DNA isolated from 26 healthy single pregnant women at different gestational stages was tested with QX200 Droplet Digital PCR. Results were compared with fetal genotypes. DNA samples purified from 20 blood pools containing a total of 1000 donors in northwest China were subjected to ddPCR to detect the gene frequency of three blood groups.</p><p><strong>Results: </strong>Ss, Kidd, and CTL2 blood groups of 26 pregnant fetuses were accurately detected by multiplex ddPCR. The multiplex ddPCR results were consistent with the Sanger sequencing results of 26 fetal blood samples after birth. The gene frequencies of the three blood groups detected by ddPCR were 9.30% for S, 90.70% for s, 48.43% for Jk^a, 51.57% for Jk^b, 66.57% for HNA-3A, and 33.43% for HNA-3B.</p><p><strong>Conclusions: </strong>It is reliable to predict fetal Ss, Kidd, and CTL2 blood groups by multiplex ddPCR. Meanwhile, we designed a simple and efficient method for inferring the gene frequency of three blood groups based on ddPCR.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ce/11/10.1177_20406207231179334.PMC10422893.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10355808","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":"Cost-effectiveness analysis of axicabtagene ciloleucel as a second-line treatment for diffuse large B-cell lymphoma in China and the United States.","authors":"Na Li,&nbsp;Jianying Lei,&nbsp;Jiahao Zhang,&nbsp;Hongfu Cai,&nbsp;Bin Zheng,&nbsp;Ting Yang,&nbsp;Maobai Liu,&nbsp;Jianda Hu","doi":"10.1177/20406207231168215","DOIUrl":"https://doi.org/10.1177/20406207231168215","url":null,"abstract":"<p><strong>Background: </strong>Axicabtagene ciloleucel (Axi-cel) is the first Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) product approved in China for treating adult patients with relapsed or refractory large B-cell lymphoma after receiving second-line or above systemic therapy. However, it cannot be widely used in clinical practice due to its high price.</p><p><strong>Objectives: </strong>To evaluate the economic value of Axi-cel fully in countries at different stages of economic development, this article, from the perspective of the medical and health system in China and the United States, evaluated the cost-effectiveness of Axi-cel in the second-line treatment of diffuse large B-cell lymphoma (DLBCL).</p><p><strong>Design: </strong>Cost effectiveness analysis of Axi-cel in the treatment of relapsed or refractory large B-cell lymphoma (LBCL).</p><p><strong>Methods: </strong>Based on the clinical trial data of ZUMA-7, a short-term decision tree and a long-term semi-Markov partitioned survival model were constructed to evaluate the cost-effectiveness of the two strategies. This model was cycled for 40 years in 1-month cycles. In this article, only direct medical costs were considered. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess the robustness of the base-case results.</p><p><strong>Results: </strong>In the baseline cost-effectiveness analysis, Axi-cel was associated with more quality-adjusted life year (QALY; 2.72 <i>versus</i> 1.46) and greater costs overall ($180,501.55 <i>versus</i> $123,221.34) than standard second-line chemotherapy in China. Moreover, the incremental cost-effectiveness ratio (ICER) of the Axi-cel group was $45,726.66/QALY, which was greater than the threshold of $37,654.5. To achieve cost-effectiveness, the price of Axi-cel must be reduced appropriately. In the United States, Axi-cel was associated with more QALYs (2.63 <i>versus</i> 1.74) and greater costs overall ($415,915.16 <i>versus</i> $289,564.34). The ICER for the Axi-cel was $142,326.94/QALY, below the set threshold of $150,000.</p><p><strong>Conclusion: </strong>Axi-cel is not a cost-effective option as second-line therapy for treating DLBCL in China. However, In the United States, Axi-cel has shown a cost-effectiveness advantage as a second-line treatment for DLBCL.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/60/c1/10.1177_20406207231168215.PMC10214081.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10350397","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":"Innovations in hematopoietic stem-cell mobilization: a review of the novel CXCR4 inhibitor motixafortide.","authors":"Zachary D Crees,&nbsp;Michael P Rettig,&nbsp;John F DiPersio","doi":"10.1177/20406207231174304","DOIUrl":"https://doi.org/10.1177/20406207231174304","url":null,"abstract":"<p><p>Hematopoietic stem-cell transplantation (HCT) and stem-cell-based gene therapies rely on the ability to collect sufficient CD34+ hematopoietic stem and progenitor cells (HSPCs), typically <i>via</i> peripheral blood mobilization. Commonly used HSPC mobilization regimens include single-agent granulocyte colony-stimulating factor (G-CSF), plerixafor, chemotherapy, or a combination of these agents. These regimens, however, frequently require multiple days of injections and leukapheresis procedures to collect adequate HSPCs for HCT (minimum = >2 × 10⁶ CD34+ cells/kg; optimal = 5-6 × 10⁶ CD34+ cells/kg). In addition, these regimens frequently yield suboptimal CD34+ HSPC numbers for HSPC-based gene-edited therapies, given the significantly higher HSPC number needed for successful gene-editing and manufacturing. Meanwhile, G-CSF is associated with common adverse events such as bone pain as well as an increased risk of rare but potentially life-threatening splenic rupture. Moreover, G-CSF is unsafe in patients with sickle-cell disease, a key patient population that may benefit from autologous HSPC-based gene-edited therapies, where it has been associated with unacceptable rates of serious vaso-occlusive and thrombotic events. Motixafortide is a novel CXCR4 inhibitor with extended <i>in vivo</i> activity (>48 h) that has been shown in preclinical and clinical trials to rapidly mobilize robust numbers of HSPCs in preparation for HCT, while preferentially mobilizing increased numbers of more primitive HSPCs by immunophenotyping and single-cell RNA expression profiling. In this review, we present a history of stem-cell mobilization and update of recent innovations in novel mobilization strategies with a specific focus on the development of motixafortide, a long-acting CXCR4 inhibitor, as a novel HSPC mobilizing agent.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/64/3f/10.1177_20406207231174304.PMC10214082.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10645860","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":"Update on the role of gemtuzumab-ozogamicin in the treatment of acute myeloid leukemia.","authors":"Mahesh Swaminathan,&nbsp;Jorge E Cortes","doi":"10.1177/20406207231154708","DOIUrl":"https://doi.org/10.1177/20406207231154708","url":null,"abstract":"<p><p>Gemtuzumab-ozogamicin (GO) is an antibody-drug conjugate (ADC) in which a monoclonal antibody targeting CD33 is covalently linked to the toxin calicheamicin. GO was initially approved by the United States Food and Drug Administration (FDA) for the treatment of adult patients with CD33⁺ acute myeloid leukemia (AML) in 2000. However, GO was recalled from the US market due to the lack of efficacy, and higher incidence of hepatotoxicities, including hepatic veno-occlusive disease (VOD), observed in phase 3 SWOG-0106 study. Since then, several other phase 3 studies have evaluated the efficacy of GO in the frontline treatment of adult patients with AML using different GO doses and schedules. The pivotal study that led to the reconsideration of GO was the French ALFA-0701 study, which used a lower and fractionated dose of GO in combination with standard chemotherapy (SC). Patients treated with the GO combination had a significantly longer survival outcome. The modified schedule also improved the toxicity profile. A systematic review and meta-analysis of over 3000 patients treated in five phase 3 studies showed that adding GO to SC improved relapse-free and overall survival. Most importantly, 6 mg/m² dose of GO was associated with higher grade ⩾3 hepatoxicities and VOD than 3 mg/m². The survival benefit was significant in the favorable and intermediate cytogenetic risk groups. This led to the reapproval of GO in 2017 for the treatment of patients with CD33⁺ AML. Currently, several clinical trials are exploring the role of GO with various combinations and in eliminating the measurable residual disease in patients with CD33⁺ AML.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/a4/10.1177_20406207231154708.PMC9943952.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10799988","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":"Genetic lesions and targeted therapy in Hodgkin lymphoma.","authors":"Zhe Li,&nbsp;Wei Mu,&nbsp;Min Xiao","doi":"10.1177/20406207221149245","DOIUrl":"https://doi.org/10.1177/20406207221149245","url":null,"abstract":"<p><p>Hodgkin lymphoma is a special type of lymphoma in which tumor cells frequently undergo multiple genetic lesions that are associated with accompanying pathway abnormalities. These pathway abnormalities are dominated by active signaling pathways, such as the JAK-STAT (Janus kinase-signal transducer and activator of transcription) pathway and the NFκB (nuclear factor kappa-B) pathway, which usually result in hyperactive survival signaling. Targeted therapies often play an important role in hematologic malignancies, such as CAR-T therapy (chimeric antigen receptor T-cell immunotherapy) targeting CD19 and CD22 in diffuse large B-cell lymphoma, while in Hodgkin lymphoma, the main targets of targeted therapies are CD30 molecules and PD1 molecules. Drugs targeting other molecules are also under investigation. This review summarizes the actionable genetic lesions, current treatment options, clinical trials for Hodgkin lymphoma and the potential value of those genetic lesions in clinical applications.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/58/10.1177_20406207221149245.PMC9841868.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10550767","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":"Impact on mental health, disease management, and socioeconomic modifications in hematological patients during the COVID-19 pandemic in Italy.","authors":"Marianna De Muro,&nbsp;Annelot Julia Janssen,&nbsp;Sergio Amadori,&nbsp;Paolo de Fabritiis,&nbsp;Dante Sabatino,&nbsp;Pasquale Niscola,&nbsp;Lorenza Torti,&nbsp;Malgorzata Monika Trawinska,&nbsp;Cristiano Tesei,&nbsp;Felice Bombaci,&nbsp;Mario Tarricone,&nbsp;Monica Bocchia,&nbsp;Carmen Fava,&nbsp;Sara Galimberti,&nbsp;Alessandra Iurlo,&nbsp;Luigia Luciano,&nbsp;Elisabetta Abruzzese","doi":"10.1177/20406207231190683","DOIUrl":"https://doi.org/10.1177/20406207231190683","url":null,"abstract":"<p><strong>Background: </strong>Hematological patients are a highly vulnerable population with an increased risk of developing severe COVID-19 symptoms due to their immunocompromised status. COVID-19 has proven to cause serious mental health issues, such as stress, anxiety, and depression in the general population. However, data on the psycho-social impact of COVID-19 on hematological patients are lacking.</p><p><strong>Objectives: </strong>This study aims to examine the psychological well-being of hematological patients in Italy during the initial period of the COVID-19 pandemic. Furthermore, it seeks to explore the association between modifications in the management of hematological diseases and employment status of these patients during the COVID-19 pandemic and the resulting mental health outcomes.</p><p><strong>Design and methods: </strong>A survey using the DASS-21 questionnaire was administered to 1105 hematological patients. Data analysis was conducted using the R software, and logistic regression analysis was performed to predict the association between hematological patient/general population and employment status with DASS scores.</p><p><strong>Results: </strong>The hematological patient population reported significantly higher levels of depression (OR 0.947, 95% CI 0.966-0.982, <i>p</i> < 0.001), anxiety (OR 0.948, 95% CI 0.939-0.958, <i>p</i> < 0.001), and stress (OR 0.984, 95% CI 0.977-0.992, <i>p</i> < 0.001) compared with the general population. A significant relationship has been found in stress between employed and unemployed patients (OR 1.015, 95% CI 1.000-1.030, <i>p</i> = 0.044), as well as in the control group (OR 1.024, 95% CI 1.010-1.039, <i>p</i> = 0.001). In addition, employment status is significantly related to depression, anxiety, and stress in both the hematological patient group and the general population.</p><p><strong>Conclusion: </strong>During the initial phase of the COVID-19 pandemic, hematological patients had elevated levels of depression, anxiety, and stress compared with the general population. The delay in their treatment and employment status played a role in their mental health outcomes. These findings emphasize the importance of further research to gain deeper insight into the long-term psychological effects and explore effective strategies for managing mental health in similar crises.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fc/bb/10.1177_20406207231190683.PMC10483981.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223038","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":"Recombinant factor IX Fc prophylaxis reduces pain and increases levels of physical activity, with sustained, long-term improvements in patients with hemophilia B: <i>post hoc</i> analysis of phase III trials using patient-reported outcomes.","authors":"Jan Astermark,&nbsp;Cédric Hermans,&nbsp;Monia Ezzalfani,&nbsp;Alaeddine Sidhom,&nbsp;Sylvaine Barbier,&nbsp;Nana Kragh,&nbsp;Aletta Falk,&nbsp;Daniel Eriksson","doi":"10.1177/20406207231170701","DOIUrl":"https://doi.org/10.1177/20406207231170701","url":null,"abstract":"<p><strong>Background: </strong>Pain is a common symptom of hemophilia that may adversely affect patients' quality of life (QoL). Previous <i>post hoc</i> analyses of prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) have been published for adults and adolescents, demonstrating improvements in health-related QoL (HRQoL) when assessed by the haemophilia-specific QoL (HaemAQoL) questionnaire.</p><p><strong>Objective: </strong>To describe in depth the evolution of QoL, pain- and activity-related domains and questions for pediatric, adolescent, and adult patients with hemophilia B treated with rFIXFc prophylaxis.</p><p><strong>Design: </strong>A <i>post hoc</i> analysis of data from a series of clinical trials.</p><p><strong>Methods: </strong>This <i>post hoc</i>, long-term analysis assessed patient-reported outcomes (PROs) from the Kids B-LONG (NCT01440946: pediatric) and B-LONG (NCT01027364: adults and adolescents) parent studies and the B-YOND (NCT01425723: all age groups) extension study.</p><p><strong>Results: </strong>Ninety-two adult and adolescent patients that started in the B-LONG study were assessed, with a median (range) duration of follow-up of 58.9 (0.0-78.4) months. The Haem-A-QoL total score was significantly reduced from baseline by 4.45 (<i>p</i> ⩽ 0.01), as were the subdomains 'physical health' (9.10; <i>p</i> = 0.001), 'sports and leisure' (11.25; <i>p</i> ⩽ 0.01), 'treatment' (2.69; <i>p</i> = 0.05), and 'view of self' (5.81; <i>p</i> = 0.002). Thirty pediatric patients that started in the Kids B-LONG study were assessed, with a median (min-max) duration of follow-up of 36.7 (9.0-59.9) months. The high level of satisfaction demonstrated by the PROs at baseline was maintained.</p><p><strong>Conclusion: </strong>rFIXFc prophylaxis reduced perceived pain and increased levels of physical activity with sustained, long-term improvements in QoL in adult and adolescent patients with hemophilia B and maintained high QoL scores in pediatric patients.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10240555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301644","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 new beginning: can omidubicel emerge as the next, viable alternative donor source?","authors":"Arpita P Gandhi,&nbsp;Laura F Newell,&nbsp;Richard T Maziarz","doi":"10.1177/20406207231192146","DOIUrl":"https://doi.org/10.1177/20406207231192146","url":null,"abstract":"<p><p>Umbilical cord blood (UCB) transplantation (CBT) has been an important alternative donor option for patients lacking matched related donor (MRD) or unrelated donor (URD) grafts. Only 30% of patients with high-risk hematologic malignancies have a human leukocyte antigen (HLA)-identical sibling; subjects without a MRD option are referred for HLA-matched URD selection, or utilize alternative donor sources such as HLA-mismatched URD, UCB, or haploidentical donor grafts. While CBT demonstrates an excellent graft-<i>versus</i>-leukemia (GVL) effect, use of UCB as a graft source is limited due to a lower cell dose that can result in delayed engraftment and an immature immune system with increased infectious risk as a consequence. Together, increased transplant related mortality (TRM) has been associated with UCB allografts. Omidubicel is an <i>ex vivo</i> expanded single cord blood product that has demonstrated rapid engraftment, improved immune reconstitution, and reduced infectious complications in clinical trials. Omidubicel has now been granted U.S. Food & Drug Administration approval to enhance neutrophil recovery and decrease infectious risk. This review will focus on CBT, benefits and barriers to using this alternative donor source, and finally the potential advancements with incorporation of omidubicel in the transplant setting for malignant and non-malignant diseases.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8b/18/10.1177_20406207231192146.PMC10469227.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10154283","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":"Immune dysregulation and potential targeted therapy in myelodysplastic syndrome.","authors":"Xiaoying Zhang,&nbsp;Xingcheng Yang,&nbsp;Ling Ma,&nbsp;Yicheng Zhang,&nbsp;Jia Wei","doi":"10.1177/20406207231183330","DOIUrl":"https://doi.org/10.1177/20406207231183330","url":null,"abstract":"<p><p>Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematological diseases and a high risk for transformation to acute myeloid leukemia (AML). The identification of key genetic alterations in MDS has enhanced our understanding of the pathogenesis and evolution. In recent years, it has been found that both innate and adaptive immune signaling are activated in the hematopoietic niche of MDS with aberrant cytokine secretion in the bone marrow microenvironment. It is also clear that immune dysregulation plays an important role in the occurrence and progression of MDS, especially the destruction of the bone marrow microenvironment, including hematopoiesis and stromal components. The purpose of this review is to explore the role of immune cells, the immune microenvironment, and cytokines in the pathogenesis of MDS. Insights into the mechanisms of these variants may facilitate the development of novel effective treatments to prevent disease progression.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/60/f2/10.1177_20406207231183330.PMC10399277.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10305916","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":"Targeting an elevated FVIII level using personalized rurioctocog alfa pegol prophylaxis in specific patient populations with hemophilia A: <i>post hoc</i> subanalysis of the randomized, phase 3 PROPEL study.","authors":"Carmen Escuriola-Ettingshausen,&nbsp;Robert Klamroth,&nbsp;Miguel Escobar,&nbsp;Oleksandra Stasyshyn,&nbsp;Srilatha Tangada,&nbsp;Werner Engl,&nbsp;Ivan Honauer,&nbsp;Hye-Youn Lee,&nbsp;Pratima Chowdary,&nbsp;Jerzy Windyga","doi":"10.1177/20406207231178596","DOIUrl":"https://doi.org/10.1177/20406207231178596","url":null,"abstract":"<p><strong>Background: </strong>The phase 3, prospective PROPEL study demonstrated that pharmacokinetic (PK)-guided prophylaxis targeting elevated factor VIII (FVIII) troughs in patients with hemophilia A resulted in lower annualized bleeding rates (ABRs) and a higher proportion of patients experiencing zero bleeds in the second 6 months of treatment when targeting a FVIII trough of 8-12% <i>versus</i> 1-3%.</p><p><strong>Objective: </strong>To investigate the benefit of PK-guided prophylaxis with rurioctocog alfa pegol targeting two FVIII trough levels in specific patient subgroups in a <i>post hoc</i> analysis using data from PROPEL.</p><p><strong>Design: </strong>This is a <i>post hoc</i> analysis of data from the PROPEL study. The design and primary outcomes of the prospective, randomized PROPEL study (NCT02585960) have been reported previously.</p><p><strong>Methods: </strong>This <i>post hoc</i> analysis reports data stratified by FVIII half-life (<i>t</i>_1/2), hemophilic arthropathy status, number of target joints at screening, previous treatment regimen, and ABR range in the 12 months before study entry.</p><p><strong>Results: </strong>Targeting an elevated FVIII trough of 8-12% was associated with higher average FVIII levels over time, regardless of FVIII <i>t</i>_1/2 at baseline. The decrease in total ABR between the 8-12% and 1-3% arms was greatest in patients with a FVIII <i>t</i>_1/2 of 6 to <12 h (0.7 <i>versus</i> 3.5); a higher number of target joints, that is, at least four target joints, at baseline (0.2 <i>versus</i> 1.6); the presence of arthropathy (0.1 <i>versus</i> 1.7); and those previously treated on-demand (0.3 <i>versus</i> 1.8).</p><p><strong>Conclusion: </strong>These results support the feasibility of targeting elevated FVIII levels using personalized rurioctocog alfa pegol prophylaxis. These benefits may be especially important in patients with a short FVIII <i>t</i>_1/2 and those receiving standard prophylaxis with frequent breakthrough bleeds, arthropathy, and target joints.</p><p><strong>Registration: </strong>ClinicalTrials.gov Identifier: NCT02585960; https://clinicaltrials.gov/ct2/show/NCT02585960.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/80/10.1177_20406207231178596.PMC10350756.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10648388","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}