Expert Review of Hematology最新文献

{"title":"Transforming hemophilia care: emerging therapeutic innovations and challenges.","authors":"Kun Huang","doi":"10.1080/17474086.2025.2527344","DOIUrl":"https://doi.org/10.1080/17474086.2025.2527344","url":null,"abstract":"<p><strong>Introduction: </strong>Hemophilia A and B are lifelong bleeding disorders traditionally managed with factor replacement therapy. While effective, this approach is limited by frequent infusions, inhibitor development, and high treatment costs, underscoring the need for innovative therapies that improve patient outcomes and quality of life.</p><p><strong>Areas covered: </strong>This review explores recent advances in hemophilia management, focusing on extended half-life factor concentrates, non-factor therapies such as bispecific antibodies and rebalancing agents, and the emergence of gene therapy as a potential functional cure. English-language studies on hemophilia therapies were searched in PubMed, Embase, Web of Science, and ClinicalTrials.gov (Jan 2014 to Apr 2025). A comprehensive literature review was conducted, covering pivotal clinical trials, real-world data, and translational research addressing both efficacy and safety considerations.</p><p><strong>Expert opinion: </strong>Innovative therapies are transforming hemophilia care, offering simplified administration, superior bleed prevention, and new hope for patients with inhibitors. Gene therapies mark a milestone, but present challenges related to durability, immune response, and cost. Personalized treatment strategies, integrating patient-specific factors and shared decision-making, are essential to optimizing outcomes. Continued research, long-term surveillance, and efforts to improve global access will define the next era of hemophilia management, moving closer to a future where patients can lead lives free from the burden of bleeding.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maintenance therapy after ASCT in newly diagnosed multiple myeloma patients: single agent <i>versus</i> combination drugs.","authors":"Enrica Antonia Martino, Ernesto Vigna, Caterina Labanca, Antonella Bruzzese, Francesco Mendicino, Giulio Caridà, Eugenio Lucia, Virginia Olivito, Noemi Puccio, Nicola Amodio, Antonino Neri, Fortunato Morabito, Massimo Gentile","doi":"10.1080/17474086.2025.2525457","DOIUrl":"10.1080/17474086.2025.2525457","url":null,"abstract":"<p><strong>Introduction: </strong>Maintenance therapy plays a crucial role in prolonging progression-free survival and overall survival in multiple myeloma. Lenalidomide remains the gold standard, as demonstrated in phase 3 trials, consistently showing superior survival compared to observation or placebo. However, both established and novel agents - such as thalidomide and pomalidomide, proteasome inhibitors (PIs), monoclonal antibodies (moAbs), and bispecific antibodies - have been investigated as alternatives to assess their efficacy and safety.</p><p><strong>Areas covered: </strong>This review delivers a comprehensive analysis of the current landscape of maintenance strategies in MM and presents the available evidence supporting the efficacy of novel agents, both as monotherapy and in combination.</p><p><strong>Expert opinion: </strong>Maintenance therapy is a critical component of MM management, capable of improving disease control and survival. Lenalidomide has demonstrated its ability to extend patients' survival, but cumulative toxicity remains a significant concern. For high-risk patients, maintenance therapy with PIs and CD38-targeting moAbs has proven to improve outcomes. However, challenges such as quality of life, cost, accessibility, and treatment resistance persist. A minimal residual disease (MRD)-adapted maintenance strategy is desirable, particularly to enable personalized treatment approaches in clinical practice.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-16"},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-transplant sorafenib effectively prevents relapse in FLT3-mutated acute myeloid leukemia.","authors":"Adrianna Spałek, Agata Wieczorkiewicz-Kabut, Patrycja Zielińska, Anna Kopińska, Krzysztof Woźniczka, Anna Koclęga, Aleksandra Butrym, Jarosław Czyż, Grzegorz Helbig","doi":"10.1080/17474086.2025.2525453","DOIUrl":"10.1080/17474086.2025.2525453","url":null,"abstract":"<p><strong>Background: </strong>Almost 50% of patients with FLT3-ITD AML relapse despite undergoing allogeneic hematopoietic stem cell transplantation (HSCT). FLT-3 inhibitors (FLT3i) can be used in a post-HSCT setting as a relapse prevention.</p><p><strong>Research design and methods: </strong>We retrospectively compared 24 FLT3-mutated AML patients receiving post-HSCT SORA with a control group of 24 FLT3-mutated AML SORA-free individuals. SORA was initiated at a median of 2.9 months after transplantation. Median dosage was 600 mg daily with median treatment duration of 8.8 months. Due to toxicities, 16/24 patients required dose modifications with 6 early SORA withdrawals. After median follow-up of 20.7 months, 1 patient relapsed in SORA-group whereas 9 relapses were observed in the control group (<i>p=</i>0.004).</p><p><strong>Results: </strong>SORA maintenance significantly improved OS and RFS probability when compared to the control group (36.3 <i>vs</i> 11.6 months; <i>p</i> = 0.01 and 95.5% and 66.7%; <i>p</i> = 0.004; respectively). SORA maintenance effectively reduced the risk of death by 93.6% for patients in complete remission with detectable measurable residual disease (<i>p</i> = 0.001). At the last follow-up, 4.2% of patients died in SORA-group when compared with 50% in the control group (<i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>SORA maintenance after HSCT diminishes the cumulative incidence of relapse as well as prolongs OS and RFS in FLT3-mutated AML.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-8"},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non- <i>MPL</i>-W515K/L mutations in myeloproliferative neoplasms: insights from two case reports and a review of the literature.","authors":"Ane Sofie Tønne Nesse, Hilde Kollsete Gjelberg, Miriam Sandnes, Rakel Brendsdal Forthun, Håkon Reikvam","doi":"10.1080/17474086.2025.2527345","DOIUrl":"https://doi.org/10.1080/17474086.2025.2527345","url":null,"abstract":"<p><strong>Background: </strong>Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) result from clonal proliferation of hematopoietic stem cells, and include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Key driver mutations in the <i>JAK2</i>, <i>CALR</i>, and <i>MPL</i> genes are important for diagnosis and differentiation of triple-negative cases. The <i>MPL</i> gene, particularly exon 10, harbors mutation hotspots influencing pathogenesis and prognosis.</p><p><strong>Research designand methods: </strong>Thisstudy presents two cases of atypical <i>MPL</i>mutations in MPN-patients and investigates the prevalence ofnon-canonical <i>MPL</i>mutationsin the literature.</p><p><strong>Results: </strong>Wereport two MPN cases with non-canonical <i>MPL</i>mutations (S204P and W515R) detected by next-generation sequencing.We also conducted a systematic review of the PubMed database,identifying 68 cases of non-W515L/K <i>MPL</i>mutations. A total of 86 mutations were identified, comprised of 32unique non-canonical mutations. W515R/S/A were the most frequent(31%), followed by V501A/M (15%) and S505N/C (13%). 59% of patientshad ET, 24% PMF and 13% post-ET/PV MF. Most mutations (71%) occurredin exon 10. 26% harbored concurrent <i>JAK2,CALR</i> and<i>MPL</i>mutations.</p><p><strong>Conclusions: </strong>Ourfindings highlight the importance of non-canonical mutations indiagnosis of MPN to prevent misclassification and improve patientmanagement. Understanding these mutations could lead to more tailoredtreatments and better outcomes in MPN patients.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An interview with Dr. Jean A. Yared on his experience as an investigator for obecabtagene autoleucel - by Reegan Burnell-Clarke (Commissioning Editor).","authors":"Jean A Yared","doi":"10.1080/17474086.2025.2524219","DOIUrl":"10.1080/17474086.2025.2524219","url":null,"abstract":"","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-3"},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in non-Hodgkin lymphoma mortality: global, regional, and national insights from 1990 to 2021.","authors":"Fangna Gu, Li Zhang","doi":"10.1080/17474086.2025.2522959","DOIUrl":"10.1080/17474086.2025.2522959","url":null,"abstract":"<p><strong>Background: </strong>Non-Hodgkin Lymphoma (NHL) is a group of hematological cancers with significant global mortality. Despite advances in treatment, mortality disparities persist across age, sex, region, and socioeconomic status, underscoring the need for a deeper understanding of global trends.</p><p><strong>Research design and methods: </strong>Data from the Global Burden of Disease Study covering 204 countries between 1990 and 2021 were analyzed. The data were stratified by sex, age, and Socio-Demographic Index (SDI). Trends were assessed using the Estimated Annual Percentage Change (EAPC), and correlations with SDI were evaluated.</p><p><strong>Results: </strong>From 1990 to 2021, global NHL deaths increased from 146,657 to 267,061, and death rates rose from 2.75 to 3.38 per 100,000 (EAPC: 0.51). Males and individuals aged 75 and older had higher mortality rates. High-SDI regions, including High-income North America (8.49 per 100,000) and High-income Asia Pacific (9.60 per 100,000), had the highest rates. Middle-SDI regions showed the most significant increases, while low-SDI regions experienced declines. Japan had a sharp rise in mortality (EAPC: 3.03), while Ethiopia had a decline (EAPC: -2.09).</p><p><strong>Conclusion: </strong>NHL mortality increased globally from 1990 to 2021, with higher burdens in males and older adults. The fastest increases were observed in middle-SDI regions, reflecting healthcare disparities.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-10"},"PeriodicalIF":2.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of pyruvate kinase activator in treating hemolytic anemias: a systematic review.","authors":"Syed Hassan Ahmed, Laila Tul Qadar, Jawad Ahmed, Zohaib Yousaf, Afsana Ansari Shaik, Muhammad Sohaib Asghar","doi":"10.1080/17474086.2025.2522295","DOIUrl":"10.1080/17474086.2025.2522295","url":null,"abstract":"<p><strong>Introduction: </strong>Pyruvate kinase (PK) is an important glycolytic enzyme responsible for erythrocytic ATP production. PK allosteric activators have been shown to increase ATP and reduce 2,3-disphosphoglycerate among red blood cells leading to improved oxygen affinity, sickling, and hemolysis. In this systematic review, we aim to evaluate the efficacy and safety of PK activators in hemolytic anemias.</p><p><strong>Methods: </strong>This study was conducted following the PRISMA guidelines. A literature search was conducted using relevant keywords over PubMed/Medline, Google Scholar, Cochrane Library, and clinicaltrial.gov, till 29 September 2024. Relevant data was extracted into a spreadsheet and synthesized qualitatively.</p><p><strong>Results: </strong>The literature search yielded 7,153 results, with seven studies ultimately included in the review. These studies involved 206 patients, 166 of whom received mitapivat and the rest received placebo. Hemoglobin response was achieved by 38.0% to 80.0% of participants receiving mitapivat, with an average increase of 0.4 to 1.7 g/dL. Most studies reported improvements in bilirubin, lactate dehydrogenase, haptoglobin, and reticulocyte levels. Adverse events (AEs) were experienced by 93.2% of participants, with rates of 93.97% and 89.7% in the intervention and control groups, respectively. However, most AEs were mild and transient, and 23.4% were graded as 3 or higher.</p><p><strong>Conclusions: </strong>In this study, PK activators, particularly mitapivat, demonstrated promising efficacy and safety profiles in managing hemolytic anemias. These agents significantly improved hemoglobin levels, markers of hemolysis, and hematopoietic response, offering a beneficial therapeutic option for various hemolytic conditions, including pyruvate kinase deficiency, sickle cell disease, and thalassemia.</p><p><strong>Registration: </strong>A protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) before study initiation, CRD42024598980.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-16"},"PeriodicalIF":2.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-106b-5p, MiR-200c-3p, and MiR-146a-5p expression as putative biomarkers for disease state in primary immune thrombocytopenia.","authors":"Reham Salah El Zaiat, Mai A H Abouelenin, Amany A Saleh, Mahmoud El-Hawy, Iman Aly Ahmedy, Manal Monir Mansour","doi":"10.1080/17474086.2025.2522298","DOIUrl":"10.1080/17474086.2025.2522298","url":null,"abstract":"<p><strong>Background: </strong>The pathophysiology of primary immune thrombocytopenia (ITP) is complicated and multifactorial, including platelet antibody formation and T cell imbalance. Emerging evidence has revealed differential miRNA expression in autoimmune disorders, including ITP. Nevertheless, the role of miR-106b-5p, miR-200c-3p, and miR-146a-5p in ITP remains unclear. Herein, we explored the potential role of these miRNAs in pediatric ITP and examined how their plasma levels influenced response to therapy.</p><p><strong>Research design and methods: </strong>Three groups were recruited in this study: newly diagnosed ITP children (<i>n</i> = 25) in group I, chronic ITP children (<i>n</i> = 25) in group II, and normal controls (<i>n</i> = 25) in group III. Plasma levels of miR-106p-5p, miR-200c-3p, and miR-146a-5p were measured by polymerase chain reaction.</p><p><strong>Results: </strong>MiR-106b-5p and miR-200c-3p were upregulated, whereas miR-146a-5p was downregulated in newly diagnosed and chronic ITP versus controls. MiR-200c-3p and miR-146a-5p were much higher in chronic ITP than newly diagnosed ITP. Lower miR-106b-5p levels were associated with complete response.</p><p><strong>Conclusions: </strong>MiR-106b-5p and miR-200c-3p were elevated, while miR-146a-5p was suppressed in ITP versus controls. Reduced miR-106b-5p indicated a full response to therapy. These markers may be useful as diagnostic ITP biomarkers. Moreover, miR-106b-5p level can be used to monitor response to therapy and as a predictor for complete response.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-8"},"PeriodicalIF":2.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current state-of-the-art of immunotherapy in follicular lymphoma.","authors":"Sean McKeague, Phil Thompson, John F Seymour","doi":"10.1080/17474086.2025.2522956","DOIUrl":"10.1080/17474086.2025.2522956","url":null,"abstract":"<p><strong>Introduction: </strong>The advent of immunotherapy has rapidly changed the treatment landscape of follicular lymphoma (FL).</p><p><strong>Areas covered: </strong>Autologous CD19 chimeric antigen receptor <i>T</i>- cell (CAR-T) products show unprecedented efficacy in third-line FL but substantial rates of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Bispecific antibodies (BSAB) achieve deep and durable responses in heavily pretreated FL patients with less severe CRS and minimal neurological toxicity. BSAB have differing routes of administration, treatment duration and CRS prophylaxis. Checkpoint inhibitors show disappointing response rates in FL. Lenalidomide and tazametostat have modest single agent activity in FL, but synergize with other forms of immunotherapy.</p><p><strong>Expert opinion: </strong>CAR-T offers a short duration of therapy with a potential plateau in progression free survival. Major disadvantages include cost, availability, requirement for lymphodepletion and toxicity. BSAB are available 'off the shelf,' have a comparably lower toxicity profile, and are ripe for combination. With both platforms, there are significant infectious risks. There are unanswered questions regarding when to use immunotherapy for FL, impact of disease burden, role of re-treatment and optimal sequencing/combinations. Moving forward, the field will need to develop new prognostic markers, reassess treatment indications, and focus on minimizing toxicity.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-13"},"PeriodicalIF":2.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obecabtagene autoleucel, a novel CD19-directed CAR T-cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia: the future for reducing toxicity and T-cell exhaustion?","authors":"Jean A Yared, Ariel Fromowitz, Mehmet Kocoglu, Nancy Hardy, Djordje Atanackovic, Aaron P Rapoport","doi":"10.1080/17474086.2025.2523551","DOIUrl":"https://doi.org/10.1080/17474086.2025.2523551","url":null,"abstract":"<p><strong>Introduction: </strong>Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL) continue to face poor outcomes despite recent advances in immunotherapy. The development of chimeric antigen receptor (CAR) T-cell therapies has transformed the treatment landscape, yet challenges such as severe cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and limited T-cell persistence have hindered their broader applicability. Obecabtagene autoleucel (obe-cel), a novel CD19-directed CAR T-cell therapy featuring a fast off-rate binding domain, represents a significant innovation aimed at optimizing the balance between efficacy and toxicity in this high-risk population.</p><p><strong>Areas covered: </strong>This review examines the pharmacologic and clinical development of obe-cel, with a focus on the unique receptor design that mimics physiologic T-cell receptor interactions to mitigate overactivation and exhaustion. Data from early-phase and pivotal trials, particularly the FELIX phase Ib/II study, are discussed in detail, highlighting efficacy outcomes such as a 77% overall remission rate and favorable safety profile with low rates of grade 3 or higher CRS (2.4%) and ICANS (7.1%). A comprehensive literature search was conducted using PubMed and clinical trial databases to identify peer-reviewed publications, reports, ongoing studies, and regulatory updates relevant to obe-cel and comparable therapies in R/R B-ALL.</p><p><strong>Expert opinion: </strong>Obe-cel represents an important conceptual advancement in CAR T-cell therapy, offering a promising alternative to existing high-affinity CD19 CARs. The integration of kinetic receptor engineering and split-dose administration appears to enhance both safety and durability of response, potentially redefining treatment goals in R/R B-ALL. As real-world experience and longer-term data accrue, obe-cel may emerge not only as a bridge to transplantation but also as a definitive therapy for select patients. The success of this approach may inform future CAR design across hematologic malignancies and support a paradigm shift toward receptor-tuned cellular immunotherapies.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}