Clinical Lymphoma, Myeloma & Leukemia最新文献

{"title":"Influence of Obesity on the Efficacy and Toxicity of Patients Undergoing Autologous Hematopoietic Cell Transplantation for Lymphoma","authors":"Andrew Lin ,&nbsp;Nicole Pearl ,&nbsp;Jessica Flynn ,&nbsp;Sean Devlin ,&nbsp;Parastoo Dahi ,&nbsp;Miguel-Angel Perales ,&nbsp;Michael Scordo ,&nbsp;Gunjan L. Shah","doi":"10.1016/j.clml.2024.09.003","DOIUrl":"10.1016/j.clml.2024.09.003","url":null,"abstract":"<div><div>Hematopoietic cell transplantation requires higher doses of chemotherapy, and practices of adjusting the weight because of concerns of organ toxicity are common. This retrospective analysis of 239 adult recipients of autologous hematopoietic cell transplantation for lymphoma assessed the effect of obesity on transplantation outcomes.</div></div><div><h3>Background</h3><div>Prior data evaluating the impact of obesity in autologous hematopoietic cell transplantation (AHCT) for lymphomas have provided differing results when assessing overall (OS) and progression-free survival (PFS). Impact on survival outcomes have been described, but direct comparison of discrete toxicities is lacking. Patients and methods: We retrospectively compared outcomes with patients divided between 3 groups: nonobese patients (n = 129), obese patients dosed on adjusted body weight (AdjBW) (n = 32), and obese patients dosed on total body weight (TBW) (n = 78).</div></div><div><h3>Results</h3><div>In multivariate analysis of OS with the nonobese group as the comparator, outcomes trended worse in obese patients dosed on AdjBW (HR 1.22, 95% CI 0.52-2.85) but were improved in obese patients dosed on TBW (HR 0.19, 95% CI 0.04-0.85, <em>P</em> = .012). PFS of obese patients dosed on AdjBW vs. the nonobese group was comparable (HR 1.19, 95% CI 0.63-2.24), but improved in obese patients dosed on TBW (HR 0.45, 95% CI 0.23-0.89, <em>P</em> = .021). Notably, no differences were noted between groups in gastrointestinal, infectious, renal, or hepatic toxicities.</div></div><div><h3>Conclusion</h3><div>In summary, our data suggest that recipients of AHCT for lymphoma should be dosed on TBW to maximize curative outcomes with no apparent increase in toxicities.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 2","pages":"Pages e90-e95"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342794","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":"Real World Data on Efficacy and Safety of EPOCH in T-Cell Lymphoma","authors":"Rachael Straining ,&nbsp;Francine Foss ,&nbsp;Molly Schiffer ,&nbsp;Kejal Amin ,&nbsp;Sonal Agarwal ,&nbsp;Iris Isufi ,&nbsp;Scott Huntington ,&nbsp;Shalin Kothari ,&nbsp;Stuart Seropian ,&nbsp;Michael Girardi ,&nbsp;Tarsheen Sethi","doi":"10.1016/j.clml.2024.09.005","DOIUrl":"10.1016/j.clml.2024.09.005","url":null,"abstract":"<div><h3>Background</h3><div>T-cell lymphomas are a heterogeneous group of lymphoid malignancies with poor outcomes. Frontline multiagent chemotherapy options include CHOP (prednisone, vincristine, cyclophosphamide, and doxorubicin), brentuximab-CHP, CHOEP, and EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin).</div></div><div><h3>Patients and Methods</h3><div>We report our single institution data for safety and efficacy of EPOCH in 38 patients with aggressive T-cell lymphoma including both peripheral T cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).</div></div><div><h3>Results</h3><div>Eighteen patients received EPOCH as first-line and 21 in the relapsed/refractory (R/R) setting. In 36 evaluable patients, the overall response rate (ORR) was 77% (95% CI, 61%-89%) with 19 (53%) patients achieving complete response (CR) (95% CI, 36%-69%). The ORR in first line and R/R settings were 80% (95% CI, 46%-94%) and 75% (95% CI, 52%-90%), respectively. Response rate was similar in African American versus Caucasian patients but was higher in CD30 negative versus positive patients. Most common grade 3/4 adverse events included cytopenias.</div></div><div><h3>Conclusions</h3><div>Overall, EPOCH was well tolerated with high response rates in first line and R/R setting.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 2","pages":"Pages e96-e102"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379170","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":"SOHO State of the Art Updates and Next Questions | CAR T Cells in T Cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma","authors":"Daniil Shmidt ,&nbsp;Maksim Mamonkin","doi":"10.1016/j.clml.2024.05.018","DOIUrl":"10.1016/j.clml.2024.05.018","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR T) therapy produced excellent activity in patients with relapsed/refractory B-lineage malignancies. However, extending these therapies to T cell cancers requires overcoming unique challenges. In the recent years, multiple approaches have been developed in preclinical models and some were tested in clinical trials in patients with treatment-refractory T-cell malignanices with promising early results. Here, we review main hurdles impeding the success of CAR T therapy in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), discuss potential solutions, and summarize recent progress in both preclinical and clinical development of CAR T therapy for these diseases.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 2","pages":"Pages 77-88"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491131","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":"The Evolving Role of Checkpoint Inhibitors in Multiple Myeloma","authors":"Ritu Chakrabarti ,&nbsp;David Siegel ,&nbsp;Noa Biran","doi":"10.1016/j.clml.2024.08.004","DOIUrl":"10.1016/j.clml.2024.08.004","url":null,"abstract":"<div><div>Multiple myeloma (MM) is a plasma cell dyscrasia characterized by production of abnormal levels of a monoclonal immunoglobulin or plasma cell deposition that leads to end organ destruction. The disease remains incurable despite advances in combination treatments with classes of medications that include proteosome inhibitors, immunomodulating agents, monoclonal antibodies, small molecule inhibitors, alkylating agents, T-cell-based immunotherapies, and others. Checkpoint inhibitors (CKP-I), though showing robust efficacy in solid tumor and lymphoma, have had limited success as single agents in the treatment of MM. Furthermore, early FDA holds on trials involving CKP-I in myeloma led to diminished enrollment and data on its potential use. Nevertheless, clearer understanding of the mechanisms of immune dysregulation and unique bone marrow biology in the pathophysiology of MM have opened the opportunity for future uses of CKP-I in multiple myeloma. Herein we provide a comprehensive review of the immunologic basis of multiple myeloma, preclinical and published data from trials utilizing CKP-I in MM patients, and future targets in CKP-I development that may provide promising opportunities in the treatment of MM.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 2","pages":"Pages 96-108"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211680","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":"Real-Life Management of Patients Aged 80 Years Old and Over With Multiple Myeloma: Results of the EMMY Cohort","authors":"T. Chalopin ,&nbsp;M. Macro ,&nbsp;O. Decaux ,&nbsp;B. Royer ,&nbsp;R. Gounot ,&nbsp;A. Bobin ,&nbsp;L. Karlin ,&nbsp;M. Mohty ,&nbsp;L. Frenzel ,&nbsp;A. Perrot ,&nbsp;S. Manier ,&nbsp;L. Vincent ,&nbsp;M. Dib ,&nbsp;B. Slama ,&nbsp;V. Richez ,&nbsp;O. Allangba ,&nbsp;P. Zunic ,&nbsp;M. Newinger-Porte ,&nbsp;C. Mariette ,&nbsp;B. Joly ,&nbsp;C. Hulin","doi":"10.1016/j.clml.2024.09.006","DOIUrl":"10.1016/j.clml.2024.09.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple myeloma patients aged 80 years and older are a population more prone to comorbidities and frailty. We aim to describe the real-life management and outcomes of this population. EMMY is a descriptive large-scale study.</div></div><div><h3>Patients</h3><div>Between 2017 and 2021 we included 4383 patients of which 894 (20.3%) were aged ≥ 80 years. Four cohorts of patients aged ≥ 80 years were analysed: line 1 (L1), line 2 (L2), line 3 (L3) or line 4+ (L4+).</div></div><div><h3>Results</h3><div>The proportion of patients ≥ 80 years old was 20.8% in L1, 21.3% in L2, 20.9% in L3 and 17.8% in L4+. L1 patients received more treatment including a proteasome inhibitor (PI) (42.9%), L2 patients received mainly an immunomodulator (IMID) (65.9%) or an anti-CD38 (31.5%). For L3, IMID was used in 71.4% than an anti-CD38 (33.5%). L4+ patients received a PI (40.6%), IMID (33.2%) or an anti-CD38 (29.1%). Regarding efficacy, the median progression-free survival was 18.4 months in L1, 15.1 months in L2, 10.4 months in L3 and 6.5 months in L4+. The median overall survival was 49 months in L1, 31.3 months in L2, 21.4 months in L3 and 13.6 months in L4+.</div></div><div><h3>Conclusion</h3><div>EMMY cohort confirmed that patients ≥ 80 years of age represent an important proportion of MM patients, in the de novo or relapse setting. This study is an important step in improving our comprehension and management of treatment in elderly patients.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 2","pages":"Pages e103-e109.e1"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496280","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":"Impact of Gut Microbiota on Lymphoma: New Frontiers in Cancer Research","authors":"Sabri Saeed Sanabani","doi":"10.1016/j.clml.2024.08.008","DOIUrl":"10.1016/j.clml.2024.08.008","url":null,"abstract":"<div><div>The gut microbiome (GMB), which is made up of various microorganisms, plays a crucial role in maintaining the health of the host. Disruptions in this delicate ecosystem, known as microbial dysbiosis, have been linked to various diseases, including hematologic malignancies such as lymphoma. This review article explores the complex relationship between the GMB and the development of lymphoma and highlights its implications for diagnostic and therapeutic approaches. It discusses how GMB influences lymphoma development directly through the presence of certain microorganisms and indirectly through changes in the immune system. The clinical relevance of GMB is highlighted and its potential utility for diagnosis, predicting treatment outcomes and developing personalized therapeutic strategies for lymphoma patients is demonstrated. The review also looks at microbiome-targeted interventions such as fecal microbiome transplantation and dietary modification, which have shown promise for treating microbial dysbiosis and improving patient outcomes. In addition, it highlights the analytical challenges and the need for further research to fully elucidate the mechanistic functions of the GMB in the context of lymphoma. This review emphasizes the critical role of GMB in lymphomagenesis and its potential for the development of diagnostic and therapeutic strategies.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 2","pages":"Pages e82-e89"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281223","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":"A Real-World Evaluation of Frontline Treatment for Acute Myeloid Leukemia With Azacitidine Plus Venetoclax.","authors":"Joseph Brandwein, David Page, Elena Liew, Mark Hnatiuk, Lauren Bolster, Marlene Hamilton, Daniel Sawler, Peng Wang","doi":"10.1016/j.clml.2025.01.024","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.024","url":null,"abstract":"<p><strong>Background: </strong>The combination of venetoclax + azacitidine (VenAza) has become the standard frontline treatment for older unfit AML patients.</p><p><strong>Methods: </strong>We analyzed outcomes using VenAza for previously untreated unfit AML patients at a single center between 2020-2024.</p><p><strong>Results: </strong>The overall response rate (ORR) was 69/105 (66%), was highest for patients with NPM1 (78%) and IDH1/2 (82%) mutations and lowest with TP53 mutations (40%). The median overall survival (OS) was 9.6 months, and 16.3 months for those achieving CR/CRi. There was no significant difference in OS between those achieving CR and CRi (p = 0.077). Patients treated between 2022-24 had a lower early death rate (8% vs. 22%) and better OS (median 10.4 vs 5.8 mos, p = 0.033) than those treated between 2020-21. There was no difference in OS between by age grouping or for patients with prior hypomethylating agent exposure. Patients with FLT3-ITD/RAS or TP53 mutations had an inferior OS compared with the other patients (median OS 8.1, 1.7 and 16 months, respectively). On multivariate analysis, achievement of CR/CRi was associated with better OS (p < 0.001), and FLT3-ITS/RAS/TP53 mutations were associated with inferior OS (p = 0.003), while ELN2022 risk group was not associated with OS. The median DFS for patients achieving CR/CRi was 7.1, 4.9 and 21 mos, for those with FLT3-ITD/RAS, TP53 and others, respectively (p = 0.003).</p><p><strong>Conclusions: </strong>This real-world analysis confirmed the prognostic importance of the mutational risk classification with VenAza treatment. OS was inferior to that reported in the VIALE A study but did improve over time.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536701","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":"Enhancing Multiple Myeloma Care: Implementation of Pharmacist-Led Prescribing of Immunomodulatory Drugs in an Academic Medical Setting.","authors":"Amy Indorf, Mary Kwok, Mark Jao, Ashley Chen, Grace T Baek, Rahul Banerjee, Kara I Cicero, Andrew J Cowan, Andrew J Portuguese, Linda Yoon, Eve M Segal","doi":"10.1016/j.clml.2025.01.013","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.013","url":null,"abstract":"<p><strong>Background: </strong>The oncology healthcare landscape has transformed and has demonstrated the need for efficient care delivery models due to improved survival resulting in larger patient panels. Pharmacists can prescribe oral anticancer agents (OAA), laboratory orders, and supportive care treatments as licensed independent practitioners (LIP) under their pharmacist license. Using immunomodulators (IMiDs) for patients with multiple myeloma (MM) has complexities with regulatory requirements for prescribing. At our institution, the care team was spending about 240 hours per month satisfying regulatory activities. We aim to characterize the effectiveness of pharmacist LIPs for patients with MM receiving IMiD treatment.</p><p><strong>Methods: </strong>A multidisciplinary quality improvement team implemented a model for OAA management with pharmacist LIPs. Patients were evaluated for IMiD adherence. Medication possession ratios (MPR) were collected using fill history for patients with 6 months of fill history pre and postpharmacist LIPs involvement, and paired McNemar's Test assessed differences in adherence. A care team survey gauged satisfaction.</p><p><strong>Results: </strong>The pharmacist patient panel comprised 246 patients. There were similar adherence rates, with an MPR of 96% preintervention and 96.55% postintervention. All survey participants recommended the pharmacist prescriber for IMiDs and reported positive reviews of pharmacist involvement.</p><p><strong>Conclusion: </strong>Management of OAAs by pharmacist LIPs is viable clinical model. The care team reduced their administrative burden while empowering pharmacists to practice at the top of their license. This framework serves as a guide for institutions to adapt and optimize OAA management in an increasingly complex therapeutic landscape.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522695","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":"Role of Pulmonary Function Tests to Predict Complications After Chimeric Antigen Receptor T-Cell Therapy.","authors":"Jeremy Walder, Felipe Soto-Lanza, Lei Feng, Sairah Ahmed, Sattva Neelapu, Amy Ayers, Horiana B Grosu, Saadia A Faiz, Loretta Nastoupil, Ajay Sheshadri","doi":"10.1016/j.clml.2025.01.019","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.019","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment of certain hematologic malignancies, but toxicities limit efficacy. The role of pre-CAR-T pulmonary function testing (PFT) to predict toxicities is unclear.</p><p><strong>Objective: </strong>Our aim was to examine the association between PFTs obtained prior to CAR-T and subsequent complications in patients with lymphoma.</p><p><strong>Study design: </strong>We conducted a retrospective study of patients who underwent standard-of-care CAR-T at our institution with pretherapy PFTs. Race-neutral normative equations from the Global Lung Initiative were used to generate percent-predicted values (PPV) for spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO). Lung function score (LFS) was calculated by combining the forced expiratory volume in the first second (FEV₁) and the diffusion capacity of the lung for carbon monoxide corrected for hemoglobin level (cDLCO) in an equally distributed manner, with higher score denoting worse lung function. Binary logistic regression models were used to compare the association of PFTs with complications after CAR-T. Cox regression models were additionally fit to identify predictors of mortality.</p><p><strong>Results: </strong>Of 218 individuals who underwent CAR-T therapy, 66 had PFTs performed within 12 months prior to lymphodepletion. Higher LFS was associated with higher risk of CRS (OR 4.3, 95% CI, 1.4-29, P = .048), after adjusting for lines of treatment. When adjusting for lines of treatment, both FEV₁ (OR = 0.96, 95% CI, 0.93-0.99, P = .05) and FVC (OR = 0.96, 95% CI 0.92-0.99, P = .03) are protective for ICANS. PFT abnormalities were not associated with early or late mortality.</p><p><strong>Conclusion: </strong>The combination of pre-CAR-T spirometry and cDLCO may help clinicians understand the risk for toxicities after CAR-T cell therapy.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499439","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":"Follicular Lymphoma: Paving the Path to Cures Through Philanthropy.","authors":"Mitchell R Smith, Michel Azoulay, Lee M Greenberger","doi":"10.1016/j.clml.2025.01.020","DOIUrl":"https://doi.org/10.1016/j.clml.2025.01.020","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457101","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}