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1.
Open Forum Infect Dis ; 10(4): ofad166, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-20234905

ABSTRACT

Respiratory viral infections (RVIs) are of major clinical importance in immunocompromised patients and represent a substantial cause of morbidity and mortality in patients with hematologic malignancies and those who have undergone hematopoietic cell transplantation. Similarly, patients receiving immunotherapy with CD19-targeted chimeric antigen receptor-modified T cells, natural killer cells, and genetically modified T-cell receptors are susceptible to RVIs and progression to lower respiratory tract infections. In adoptive cellular therapy recipients, this enhanced susceptibility to RVIs results from previous chemotherapy regimens such as lymphocyte-depleting chemotherapy conditioning regimens, underlying B-cell malignancies, immune-related toxicities, and secondary prolonged, profound hypogammaglobulinemia. The aggregated risk factors for RVIs have both immediate and long-term consequences. This review summarizes the current literature on the pathogenesis, epidemiology, and clinical aspects of RVIs that are unique to recipients of adoptive cellular therapy, the preventive and therapeutic options for common RVIs, and appropriate infection control and preventive strategies.

2.
Support Care Cancer ; 31(6): 350, 2023 May 25.
Article in English | MEDLINE | ID: covidwho-20231187

ABSTRACT

PURPOSE: CAR-T programs will burden increasingly on healthcare systems, since the implementation of these therapies involves: multidisciplinary team collaboration, post-infusion hospitalization with risk of life-threatening toxicities, frequent in hospital visits and prolonged follow-up which heavily influence patients' quality of life. In this review we propose an innovative, telehealth-based, model for monitoring CAR-T patients: this method was used for managing a case of COVID-19 infection occurred two weeks after CAR-T cell infusion. METHODS: Several benefits for management of all these aspects of CAR-T programs could be made using telemedicine: for example, telemedicine real-time clinical monitoring could reduce the COVID-19 contagion risks for CAR-T patients. RESULTS: Our experience confirmed feasibility and utility of this approach in a real-life case. We believe that use of telemedicine for CAR-T patients could improve: the logistics of toxicity monitoring (frequent vital sign checks and neurologic assessments), the multidisciplinary team communication (patient selection, specialists consulting, coordination with pharmacists, etc.), the decrease in hospitalization time and the reduction of ambulatory visits. CONCLUSIONS: This approach will be fundamental for future CAR-T cell program development, enhancing patients' quality of life and cost-effectiveness for healthcare systems.


Subject(s)
COVID-19 , Receptors, Chimeric Antigen , Telemedicine , Humans , Pandemics/prevention & control , Quality of Life , Cell- and Tissue-Based Therapy
3.
Ann Hematol ; 102(7): 1837-1843, 2023 Jul.
Article in English | MEDLINE | ID: covidwho-20231010

ABSTRACT

Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL). Several risk factors including CAR-T cell-related toxicities and their treatments often lead to infectious complications (ICs); however, the pattern and timeline is not well established. We evaluated ICs in 48 patients with R/R B-cell NHL following CAR-T cell therapy at our institution. Overall, 15 patients experienced 22 infection events. Eight infections (4 bacterial, 3 viral and 1 fungal) occurred within the first 30 days and 14 infections (7 bacterial, 6 viral, 1 fungal) between days 31 to 180 following CAR-T infusion. Most infections were mild-to-moderate and fifteen infections involved the respiratory tract. Two patients developed mild-to-moderate COVID-19 infection and one patient a cytomegalovirus reactivation after CAR-T infusion. Two patients developed IFIs: one case each of fatal disseminated candidiasis and invasive pulmonary aspergillosis at day 16 and 77, respectively. Patients with more than 4 prior antitumor regimens and patient's ≥ 65 years had a higher infection rate. Infections in patients with relapsed/refractory B-cell NHL are common after CAR-T despite the use of infection prophylaxis. Age ≥ 65 years and having > 4 prior antitumor treatments were identified as risk factors for infection. Fungal infections carried significant impact in morbidity and mortality, suggesting a role for increase fungal surveillance and/or anti-mold prophylaxis following high-dose steroids and tocilizumab. Four of ten patients developed an antibody response following two doses of SARS-CoV-2 mRNA vaccine.


Subject(s)
COVID-19 , Lymphoma, B-Cell , Receptors, Chimeric Antigen , Humans , Aged , COVID-19 Vaccines , SARS-CoV-2 , Lymphoma, B-Cell/therapy , Cell- and Tissue-Based Therapy , Antigens, CD19
4.
2023 International Conference on Advances in Intelligent Computing and Applications, AICAPS 2023 ; 2023.
Article in English | Scopus | ID: covidwho-2292357

ABSTRACT

In recent years, the number of online courses in India has skyrocketed especially due to the Covid pandemic. The most significant increments have happened in degree colleges, where 85% concur that internet based courses are important for their drawn-out procedure when contrasted with 60% in 2015. The distribution of online courses has evolved dramatically as technology has advanced. Web-based platform provides new challenges for both teachers and students. Teachers should be clear about the effectiveness of online learning in teaching students. For that, the possibilities of online learning should be compared with traditional learning. Students are evaluated based on their focus on online learning. This study aims to determine the efficacy of online courses by predicting student performance in an e-learning system. These research findings evaluate modern learning methods, highlight students' potential and help teachers understand how to assess and lead students on online platforms. © 2023 IEEE.

5.
Stem Cell Reports ; 17(9): 1959-1975, 2022 09 13.
Article in English | MEDLINE | ID: covidwho-2305537

ABSTRACT

In vitro tissue models hold great promise for modeling diseases and drug responses. Here, we used emulsion microfluidics to form micro-organospheres (MOSs), which are droplet-encapsulated miniature three-dimensional (3D) tissue models that can be established rapidly from patient tissues or cells. MOSs retain key biological features and responses to chemo-, targeted, and radiation therapies compared with organoids. The small size and large surface-to-volume ratio of MOSs enable various applications including quantitative assessment of nutrient dependence, pathogen-host interaction for anti-viral drug screening, and a rapid potency assay for chimeric antigen receptor (CAR)-T therapy. An automated MOS imaging pipeline combined with machine learning overcomes plating variation, distinguishes tumorspheres from stroma, differentiates cytostatic versus cytotoxic drug effects, and captures resistant clones and heterogeneity in drug response. This pipeline is capable of robust assessments of drug response at individual-tumorsphere resolution and provides a rapid and high-throughput therapeutic profiling platform for precision medicine.


Subject(s)
Antineoplastic Agents , Organoids , Antineoplastic Agents/pharmacology , Drug Evaluation, Preclinical/methods , Humans , Microfluidics , Precision Medicine
6.
J Community Psychol ; 2022 Sep 09.
Article in English | MEDLINE | ID: covidwho-2304642

ABSTRACT

Resilience is of the upmost importance to deal with everyday problems faced by communities. The concept of community resilience is gaining prominence in disaster management policy and practice, and it has been shown to be an important factor during pandemic recovery such as during the SARS-CoV-2 outbreak. We present an instrument for community resilience assessment adapted for disasters like the pandemics. The instrument was based on the theory-based and evidence-informed Communities Advancing Resilience Toolkit (CART) Assessment Survey, adapted for the first time to Portuguese. Another strong feature of this study relates to the targeted participants, namely human service workers (598). They are key informants for their close involvement with communities. This version of the CART was reliable. A confirmatory factor analysis indicated a good relationship between the observed variables and their underlying latent constructs. Moreover, tests for measurement invariance across participants showed that differences in factor variances and covariances were not attributable to age-based differences in the properties of the scales themselves. Our findings support the fundamental idea that it is worthwhile to have an instrument to measure community resilience. Thus, our study adds to the evaluation of the CART, supporting its value as a robust instrument to measure resilience at the community level in different countries.

7.
IATSS Research ; 2023.
Article in English | Scopus | ID: covidwho-2270622

ABSTRACT

In this study, we develop a system to provide information on the sterilization of baggage carts and arriving passenger baggage to airport (Hereafter referred as arrival baggage) by using ultraviolet (UV) sterilization and information communication technology as border quarantine measures at airports. This system sterilizes arrival baggage and baggage carts by UV irradiation, and allows passengers to easily view the sterilization information recognized by radio frequency indentation technology. This is to provide safety and security not only to passengers, but also to staff, who may come into direct contact with the arrival baggage, of airport, airline, customs, and so on. In addition, the passengers can be provided with baggage tracking information, such as the current location and estimated delivering time of the baggage. This makes it possible to keep social distancing at baggage claims as an infection prevention. Furthermore, we verify the feasibility of the developed system and identify the issues to be addressed for its practical application through a demonstration of proof of concept at Central Japan International Airport. © 2022 International Association of Traffic and Safety Sciences

8.
Cell Mol Immunol ; 20(4): 351-364, 2023 04.
Article in English | MEDLINE | ID: covidwho-2287148

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this "two-cell" (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.


Subject(s)
COVID-19 , Receptors, Chimeric Antigen , Humans , SARS-CoV-2/metabolism , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Caspofungin , Felodipine , Cytokine Release Syndrome/drug therapy , Inflammation , Cytokines/metabolism
9.
Front Pediatr ; 11: 1076686, 2023.
Article in English | MEDLINE | ID: covidwho-2279640

ABSTRACT

This report describes a pediatric patient who underwent chimeric antigen receptor (CAR) T-cell therapy for refractory B-cell acute lymphoblastic leukemia (B-ALL) four years prior, with resultant hypogammaglobulinemia for which he was receiving weekly subcutaneous immune globulin. He presented with persistent fever, dry cough, and a tingling sensation in his toes following a confirmed COVID-19 infection 3 weeks prior. His initial nasopharyngeal SARS-CoV-2 PCR was negative, leading to an extensive workup for other infections. He was ultimately diagnosed with persistent lower respiratory tract COVID-19 infection based on positive SARS-CoV-2 PCR from bronchoalveolar lavage (BAL) sampling. He was treated with a combination of remdesivir (antiviral) and casirivimab/imdevimab (combination monoclonal antibodies) with immediate improvement in fever, respiratory symptoms, and neurologic symptoms.

10.
Socioecon Plann Sci ; 87: 101549, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2252667

ABSTRACT

In order to address one of the most challenging problems in hospital management - patients' absenteeism without prior notice - this study analyses the risk factors associated with this event. To this end, through real data from a hospital located in the North of Portugal, a prediction model previously validated in the literature is used to infer absenteeism risk factors, and an explainable model is proposed, based on a modified CART algorithm. The latter intends to generate a human-interpretable explanation for patient absenteeism, and its implementation is described in detail. Furthermore, given the significant impact, the COVID-19 pandemic had on hospital management, a comparison between patients' profiles upon absenteeism before and during the COVID-19 pandemic situation is performed. Results obtained differ between hospital specialities and time periods meaning that patient profiles on absenteeism change during pandemic periods and within specialities.

11.
International Journal of Consumer Studies ; 47(2):453-473, 2023.
Article in English | ProQuest Central | ID: covidwho-2236825

ABSTRACT

The COVID‐19 pandemic has put online shopping at the forefront of retailing;however, the issue related to shopping cart abandonment remains an eternal nemesis of e‐retailers. To understand extant research on online shopping cart abandonment (OSCA), a framework‐based systematic literature review was conducted with the purpose of gaining more insights into existing studies in this context. Specifically, this review examined the literature related to OSCA in terms of theory, context, characteristics, and methods to provide (i) a comprehensive review of the current state of research and (ii) constructive future research agenda in the area. Using scientific procedures, a total of 52 research articles were retrieved from Scopus and Web of Science databases published during the period 2003–2022. The results revealed that most research was founded by the stimulus‐organism‐response (S‐O‐R) model and the buyer behavior theory, focused in the context of the United States and China, and appeared to use quantitative methods. As a result, this review is expected to assist researchers in better understanding the OSCA context, thus paving the way for further research and development in the area. In addition, providing practitioners with a better panorama to address the issue by expanding the literature review and highlighting the inhibiting factors of OSCA.

12.
Int J Hematol ; 117(5): 765-768, 2023 May.
Article in English | MEDLINE | ID: covidwho-2227452

ABSTRACT

SARS-CoV-2 virus is a single-stranded enveloped RNA virus, which causes coronavirus disease. Most of the immunocompetent patients with SARS-CoV-2 infection do have mild to moderate respiratory illness; however, in immunocompromised patients, the course of infection is unpredictable with high rates of infectivity and mortality. So, it is important to identify the immunocompromised patients early and establish the course of treatment accordingly. Here, we describe a 25-year-old male with background of B cell ALL, post-BMT and CAR-T therapy who received treatment with remdesivir and vaccination and was followed up for six months from the onset of symptoms to post vaccination, which showed resolution of symptoms and improvement of immunological markers. Here, we review the literature concerning the course and treatment of SARS-CoV-2 infection aimed at achieving cure in this patient.


Subject(s)
COVID-19 , Receptors, Chimeric Antigen , Male , Humans , Adult , SARS-CoV-2 , COVID-19 Drug Treatment
13.
Journal of Pharmaceutical Negative Results ; 13:3897-3905, 2022.
Article in English | EMBASE | ID: covidwho-2206774

ABSTRACT

Introduction: The machine learning and artificial intelligence tools, party and random forest can be used to evaluate surveillance data for better outcomes. The primary objective of the study was to evaluate the utility and reliability of machine learning and artificial intelligence model primary data for the Influenzas Like illness (ILI) Surveillance of patients attending fever OPD in a tertiary care hospital during covid 19 pandemic. The secondary objective was to estimate model statistics to measure the effect of parameters. Methodology: This is a secondary data analysis study based on surveillance data in the tertiary care hospital attached to medical college. The data of 3723 cases was collected by Surveillance team for Influenzas Like Illness (ILI) under Department of Community Medicine in Fever OPD during covid pandemic from 23 March 2020 to 30 June 2020. Data consisted (11) variables. Data was analysed using R Software (4.2.2). Machine learning (ML) and Artificial Intelligence tool party and random forest were applied. Result(s): The random forest model performed better than Party model with model accuracy of 0.9557, AUC of random forest model were 87.4% (sensitivity 0.9533, specificity 0.9685), 89.7% (sensitivity 0.9059, specificity 0.9957) and 88.3% (Sensitivity 0.965, Specificity 0.9527) for confirmed, probable and suspected with different cut-offs. The model found Severity of Patient (Mild, Moderate, Severe), the day of Fever OPD Visit, nature of illness (is asymptomatic?) and age of patient as the most significant factors in decreasing order by mean decrease in Accuracy while the Severity of Patient (Mild, Moderate, Severe), the day of Fever OPD Visit, age of patient and number of symptomatic Complaint (NOC) were found the most significant factors in decreasing order by mean decrease in Gini to predict Covid-19 Test Results. Conclusion(s): The party algorithm was consistent for train and test dataset while for the random forest results were good on train dataset while same model had seen difficulty in prediction class for the test dataset. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

14.
Heliyon ; 8(11): e11293, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2086260

ABSTRACT

Online shopping has accelerated during to the pandemic and an increase in online shopping cart abandonment (SCA) was also evident. The growth of online shopping is contributed by the rising middle class, high consumer spending, millennials, and a tech-savvy population which is valuable to the growth of e-commerce. This study aimed to predict the factors that affect SCA during the COVID-19 Pandemic utilizing the SEM-RFC hybrid. Several factors such as self-efficacy, attribute conflicts, hesitation at checkout, emotional ambivalence, choice process satisfaction, attitude, subjective norms, and perceived behavioral control were analyzed simultaneously. This study integrated the cognition-affect-behavior paradigm with the Theory of Planned Behavior to provide a conceptual framework measured through an online survey questionnaire answered by 1015 valid responses collected by convenience sampling. Results showed that Attitude, Attribute Conflict, Self-Efficacy, and Emotional Ambivalence are the primary significant factors affecting SCA. Amidst the pandemic, consumers still value the ease of use, convenience and safety of the mobile online shopping applications that they have, which they do not positively experience at this time. The findings of this study may be applied and extended by researchers, online retailers, and businesses to understand consumer's abandonment intentions. Moreover, the results and framework of this study may be capitalized on by the business sector to create marketing strategies and develop business models for a sustainable online shopping business worldwide.

15.
Clin Transl Immunology ; 11(10): e1421, 2022.
Article in English | MEDLINE | ID: covidwho-2085016

ABSTRACT

Objectives: Despite advances in antibody treatments and vaccines, COVID-19 caused by SARS-CoV-2 infection remains a major health problem resulting in excessive morbidity and mortality and the emergence of new variants has reduced the effectiveness of current vaccines. Methods: Here, as a proof-of-concept, we engineered primary CD8 T cells to express SARS-CoV-2 Spike protein-specific CARs, using the extracellular region of ACE2 and demonstrated their highly specific and potent cytotoxicity towards Spike-expressing target cells. To improve on this concept as a potential therapeutic, we developed a bispecific T cell engager combining ACE2 with an anti-CD3 scFv (ACE2-Bite) to target infected cells and the virus. Results: As in CAR-T cell approach, ACE2-Bite endowed cytotoxic cells to selectively kill Spike-expressing targets. Furthermore, ACE2-Bite neutralized the pseudoviruses of SARS-CoV, SARS-CoV-2 wild-type, and variants including Delta and Omicron, as a decoy protein. Remarkably, ACE2-Bite molecule showed a higher binding and neutralization affinity to Delta and Omicron variants compared to SARS-CoV-2 wild-type Spike proteins. Conclusion: In conclusion, these results suggest the potential of this approach as a variant-proof, therapeutic strategy for future SARS-CoV-2 variants, employing both humoral and cellular arms of the adaptive immune response.

16.
International Journal of Consumer Studies ; 2022.
Article in English | Web of Science | ID: covidwho-2070516

ABSTRACT

The COVID-19 pandemic has put online shopping at the forefront of retailing;however, the issue related to shopping cart abandonment remains an eternal nemesis of e-retailers. To understand extant research on online shopping cart abandonment (OSCA), a framework-based systematic literature review was conducted with the purpose of gaining more insights into existing studies in this context. Specifically, this review examined the literature related to OSCA in terms of theory, context, characteristics, and methods to provide (i) a comprehensive review of the current state of research and (ii) constructive future research agenda in the area. Using scientific procedures, a total of 52 research articles were retrieved from Scopus and Web of Science databases published during the period 2003-2022. The results revealed that most research was founded by the stimulus-organism-response (S-O-R) model and the buyer behavior theory, focused in the context of the United States and China, and appeared to use quantitative methods. As a result, this review is expected to assist researchers in better understanding the OSCA context, thus paving the way for further research and development in the area. In addition, providing practitioners with a better panorama to address the issue by expanding the literature review and highlighting the inhibiting factors of OSCA.

17.
Int J Environ Res Public Health ; 19(19)2022 Sep 27.
Article in English | MEDLINE | ID: covidwho-2065932

ABSTRACT

BACKGROUND: There is a lack of knowledge regarding the actionable key predictive factors of homelessness in psychiatric populations. Therefore, we used a machine learning model to explore the REHABase database (for rehabilitation database-n = 3416), which is a cohort of users referred to French psychosocial rehabilitation centers in France. METHODS: First, we analyzed whether the different risk factors previously associated with homelessness in mental health were also significant risk factors in the REHABase. In the second step, we used unbiased classification and regression trees to determine the key predictors of homelessness. Post hoc analyses were performed to examine the importance of the predictors and to explore the impact of cognitive factors among the participants. RESULTS: &nbsp;First, risk factors that were previously found to be associated with homelessness were also significant risk factors in the REHABase. Among all the variables studied with a machine learning approach, the most robust variable in terms of predictive value was the nature of the psychotropic medication (sex/sex relative mean predictor importance: 22.8, σ = 3.4). Post hoc analyses revealed that first-generation antipsychotics (15.61%; p < 0.05 FDR corrected), loxapine (16.57%; p < 0.05 FWER corrected) and hypnotics (17.56%; p < 0.05 FWER corrected) were significantly associated with homelessness. Antidepressant medication was associated with a protective effect against housing deprivation (9.21%; p < 0.05 FWER corrected). CONCLUSIONS: Psychotropic medication was found to be an important predictor of homelessness in our REHABase cohort, particularly loxapine and hypnotics. On the other hand, the putative protective effect of antidepressants confirms the need for systematic screening of depression and anxiety in the homeless population.


Subject(s)
Antipsychotic Agents , Ill-Housed Persons , Loxapine , Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Ill-Housed Persons/psychology , Humans , Hypnotics and Sedatives , Machine Learning , Psychotropic Drugs/therapeutic use
18.
Clinical Lymphoma, Myeloma and Leukemia ; 22(Supplement 2):S411, 2022.
Article in English | EMBASE | ID: covidwho-2062040

ABSTRACT

Context: CARTITUDE-2 (NCT04133636) Cohort A is assessing cilta-cel in lenalidomide-refractory patients with progressive MM after 1-3 prior LOT. Objective(s): To present updated results from CARTITUDE-2 Cohort A. Design(s): Phase 2, multicohort study. Patient(s): Lenalidomide-refractory patients with progressive MM after 1-3 prior LOT (PI and IMiD included) and no previous exposure to BCMA-targeting agents. Intervention(s): Single cilta-cel infusion (target dose 0.75x106 CAR+ viable T-cells/kg) after lymphodepletion Main Outcome Measure(s): Primary endpoint was minimal residual disease (MRD) negativity at 10-5. Management strategies were used to reduce risk of movement/neurocognitive adverse events (MNTs). Pharmacokinetics (PK) (Cmax/Tmax of CAR+T-cell transgene levels), cytokine release syndrome (CRS)-related cytokines over time, peak cytokine levels by response/CRS, association of cytokine levels with immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR+T-cell CD4/CD8 ratio by response/CRS/ICANS are being evaluated. Result(s): As of January 2022 (median follow-up [MFU] 17.1 months), 20 patients (65% male;median age 60 years;median 2 prior LOT;95% refractory to last LOT) received cilta-cel. Overall response rate was 95% (90% >=complete response;95% >=very good partial response). Median times to first and best response were 1.0 month and 2.6 months, respectively. All 16 MRD-evaluable patients achieved MRD negativity at 10-5. Median duration of response was not reached. At 12 months, event-free rate was 79% and progression-free survival rate was 75%. 95% of patients had CRS (gr3/4 10%);median time to onset was 7 days and median duration was 3 days. Neurotoxicity was reported in 30% of patients (5 gr1/2;1 gr3/4) and ICANS in 15% (all 3 gr1/2);1 patient had gr2 facial paralysis. No MNTs were observed. 1 death occurred due to COVID-19 (treatment-related), 2 due to progressive disease, and 1 due to sepsis (not treatment-related). Preliminary PK analyses showed peak CAR-T cell expansion at day 10.5;median persistence was 153.5 days. Conclusion(s): At MFU of 17.1 months, a single cilta-cel infusion resulted in deep and durable responses in lenalidomide-refractory MM patients with 1-3 prior LOT. We will present updated PK/cytokine/CAR-T subset analyses and clinical correlation to provide novel insights into biological correlates of efficacy/safety in this population. Copyright © 2022 Elsevier Inc.

19.
Front Oncol ; 12: 902301, 2022.
Article in English | MEDLINE | ID: covidwho-2043505

ABSTRACT

Chimeric antigen receptor-T (CAR-T) cell therapy is a breakthrough for B-cell hematological malignancies but is commonly associated with cytokine release syndrome and neurotoxicity and is occasionally complicated by neurological symptoms, such as cognitive disturbances. Currently, no effective treatments for CAR-T therapy-related cognitive impairment are available. Here, we present a 22-year-old patient with cognitive impairment who was treated with CAR-T cells as a salvage therapy for Burkitt lymphoma. One month after CAR-T cell infusion, he experienced memory loss that mainly manifested as forgetting recent-onset events. Two months of rehabilitation and hyperbaric oxygen therapy failed to provide clinical improvement. Subsequently, the patient improved with oral oxiracetam for 5 months. However, after 10 months of withdrawal, he showed significantly worse memory decline. Then, he began to take sodium oligomannate (22 February 2021). Follow-up testing at 6 and 12 months revealed maintenance of memory gains with sodium oligomannate alone or in combination with rivastigmine. Our case shows that CAR-T therapy may compromise cognitive function and that sodium oligomannate may have partial efficacy in restoring cognitive performance and activities of daily living. This may provide insights for further applications of sodium oligomannate for neurological symptoms, especially cognitive deficits following CAR-T cell therapy.

20.
Clinical Lymphoma Myeloma and Leukemia ; 22:S413, 2022.
Article in English | ScienceDirect | ID: covidwho-2042281

ABSTRACT

Context: Triple class exposed/refractory multiple myeloma (MM) represents an unmet medical need because there is no standard of care and overall survival (OS) does not exceed 9 months. B-cell maturation antigen (BCMA) has appeared as an interesting target to treat MM. Objective: To indirectly compare the time to access therapy and hospitalization as well as the toxicity and efficacy of BCMA bispecific monoclonal antibodies (BiAbs) and CAR-T. Design: An observational retrospective study was designed including MM patients treated with BCMA CAR-T or BiAbs in clinical trials at the Hospital of Salamanca (October 2018–April 2022). Patients or Other Participants: Forty-nine patients were treated with BCMA therapy. Intervention: N/A. Main Outcome Measures: The time to access the treatment and hospitalization, global responses, cytokine release syndrome (CRS), neurotoxicity, infections, progression-free survival (PFS), and OS. Results: Twenty-seven patients (55.1%) received CAR-T and 22 (44.9%) received BiAbs. Thirty-nine (79.6%) patients were triple exposed and 28 (57.1%) were triple refractory. Patients who received BiAbs were treated earlier (12 vs. 56 days;P<0.001) and were hospitalized for less time (13 vs. 21 days;P=0.018). Overall response rate was superior in CAR-T patients (100% vs. 52.4%;P<0.001) as was percentage of CR (70.4% vs. 47.6%;P=0.110). Incidence of CRS was higher in the CAR-T group than the BiAbs group (92.6% vs. 68.2%;P=0.028) as were the percentages of grade 4 neutropenia (92.6% vs. 22.7%;P<0.001) and thrombocytopenia (70.4% vs. 9.1%;P<0.001). Infections were more frequent in the BiAbs group (especially between the first and third month of treatment initiation, 55.6% vs. 14.8%;P=0.004), including COVID-19 infection (50.0% vs. 29.6%;P=0.002). With a median follow-up of 14.3 months (1.1–41.8), PFS was superior in patients treated with CAR-T (18.9 vs. 6.1 months;P=0.045) as was OS (not reached vs. 25.5 months;P=0.016). Conclusions: The times to access therapy and hospitalization were shorter in patients treated with BiAbs. The incidences of CRS and cytopenia were higher in the CAR-T group, but mid-term and COVID-19 infections were more frequent in the BiAbs group. Response, PFS, and OS were superior in patients treated with CAR-T than those treated with BiAbs.

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