Expanding the clinical utility of liquid biopsy by using liquid transcriptome and artificial intelligence.

Most of the current utilization of liquid biopsy (LBx) is based on analyzing cell-free DNA(cfDNA). There is limited data on using cell-free RNA (cfRNA) levels (liquid transcriptome) in LBx. The major hurdles for using liquid transcriptome is its low level in circulation and the dilutional effects of various tissues that may pour their RNA into circulation.

Liquid biopsy for evaluating mutations and chromosomal aberrations in cerebrospinal fluid from patients with primary or metastatic CNS tumors.

Background: Cytopathology analysis of cerebrospinal fluid (CSF) is limited in detecting tumors in patients with suspected primary or metastatic central nervous system (CNS) malignancy. We investigated the use of CSF liquid biopsy (LBx) to detect neoplastic processes in the CNS.

Methods: Cell-free DNA (cfDNA) from the CSF of patients with suspected metastatic (N = 106) or primary CNS (N = 23) tumors was deep sequenced using a 302-gene panel.

Updates on the Biological Heterogeneity of Mantle Cell Lymphoma.

Advancements in mantle cell lymphoma (MCL) have illuminated the disease's molecular diversity, leading to a wide variation in the outcomes observed in MCL. Current prognostic risk scores are continuously revised to incorporate new updates in the mechanistic or biologic understanding of MCL. Nevertheless, key high-risk features of MCL associated with rapid disease progression and poor survival, such as mutations, complex karyotypes, and blastoid or pleomorphic morphologies, remain absent from available prognostic tools.

Perspectives on Current Challenges and Emerging Approaches for Lymphoma Management From the First Bridging the Gaps in Leukemia, Lymphoma, and Multiple Myeloma Conference.

Recent years have brought a much-needed paradigm shift to the management and treatment of mature B-cell lymphomas. Pathophysiologic and clinical heterogeneity within the various subtypes have historically contributed to treatment challenges and differences in outcomes. Novel genomic tools and therapeutic modalities give promise for improved patient outcomes, but are also making treatment planning increasingly complex.

Treatment failure patterns in early versus late introduction of CAR T-cell therapy in large B-cell lymphoma.

CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has recently been approved as second-line treatment for relapsed/refractory large B-cell lymphoma (LBCL). This study compares patterns of disease relapse and progression across patients receiving CAR-T as second-line (early administration) versus third or subsequent lines (late administration). We analyzed 354 patients treated with Axicabtagene ciloleucel (71%) and Lisocabtagene maraleucel (29%); 80 (23%) received early administration, and 274 (77%) late administration.

Comprehensive Review of Early and Late Toxicities in CAR T-Cell Therapy and Bispecific Antibody Treatments for Hematologic Malignancies.

Chimeric antigen receptor T-cell (or CAR-T) therapy and bispecific antibodies (BsAbs) have revolutionized the treatment of hematologic malignancies, offering new options for relapsed or refractory cases. However, these therapies carry risks of early complications, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and delayed issues like graft-versus-host disease (GVHD), infections, and secondary cancers. Effective management requires early diagnosis using advanced biomarkers and imaging, along with prompt interventions involving immunosuppressants, corticosteroids, and cytokine inhibitors.

Cancer survivor preferences on the timing and content of interventions to mitigate financial toxicity associated with cancer treatment.

Purpose: Despite growing research on financial toxicity among cancer survivors, large gaps remain in understanding how to intervene to minimize financial toxicity. Uptake and efficacy of interventions mitigating cancer financial toxicity, though promising, remain limited and inconsistent. To date, survivor preferences for financial toxicity interventions are underexplored.

Prevalence of non-Hodgkin lymphoma patients at high-risk of failure after CAR T-cell therapy eligible for bridging radiation therapy.

Background And Purpose: The aim of this study was to determine the prevalence of patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) meeting high-risk criteria for early relapse after CD19 CAR T-cell therapy (CART) who have disease encompassable in a standard radiation therapy (RT) plan (defined as <5 malignant lesions) and may benefit from bridging RT prior to CD19 CART.

Materials And Methods: This is a single-center, retrospective study of patients with R/R NHL who received CD19 CART from 2018 to 2022. Eligible patients had pre-apheresis radiologic studies available.

Subsequent Malignancies After CD19-Targeted Chimeric Antigen Receptor T Cells in Patients With Lymphoma.

Chimeric antigen receptor (CAR) T cells are an established treatment for B cell non-Hodgkin lymphomas (B-NHL). With the remarkable success in improving survival, understanding the late effects of CAR T cell therapy is becoming more relevant. The aim of this study is to determine the incidence of subsequent malignancies in adult patients with B-NHL.

Clinical Outcomes of Immune Checkpoint Inhibitors in Unique Cohorts Underrepresented in Clinical Trials.

Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018.

Using Targeted Transcriptome and Machine Learning of Pre- and Post-Transplant Bone Marrow Samples to Predict Acute Graft-versus-Host Disease and Overall Survival after Allogeneic Stem Cell Transplantation.

Acute graft-versus-host disease (aGvHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). We performed RNA analysis of 1408 candidate genes in bone marrow samples obtained from 167 patients undergoing HSCT. RNA expression data were used in a machine learning algorithm to predict the presence or absence of aGvHD using either random forest or extreme gradient boosting algorithms.

Humoral and cellular immune responses against SARS-CoV-2 post-vaccination in immunocompetent and immunocompromised cancer populations.

Unlabelled: Cancer patients are at risk for severe coronavirus disease 2019 (COVID-19) outcomes due to impaired immune responses. However, the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is inadequately characterized in this population. We hypothesized that cancer vs non-cancer individuals would mount less robust humoral and/or cellular vaccine-induced immune SARS-CoV-2 responses.

Treatment Outcomes with Standard of Care in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Real-World Data Analysis.

Introduction: Despite new therapies for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), treatments with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents continue to be commonly used.

Methods: This retrospective study utilized longitudinal data from 4226 real-world electronic health records to characterize outcomes in patients with R/R DLBCL. Eligible patients were diagnosed with DLBCL between January 2010 and March 2022 and had R/R disease treated with ≥ 1 prior systemic line of therapy (LOT), including ≥ 1 anti-CD20-containing regimen.

Phase 1b dose-finding study of rituximab, lenalidomide, and ibrutinib (R2I) in patients with relapsed/refractory mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare non-Hodgkin lymphoma that frequently becomes chemoresistant over time. The distinct mechanisms of ibrutinib and lenalidomide provided a judicious rationale to explore the combination with anti-CD20 immunotherapy. In this phase 1b study (NCT02446236), patients ( = 25) with relapsed/refractory MCL received rituximab with escalating doses of lenalidomide (days 1-21) and ibrutinib 560 mg (days 1-28) of 28-day cycles.

Identifying an optimal fludarabine exposure for improved outcomes after axi-cel therapy for aggressive B-cell non-Hodgkin lymphoma.

Fludarabine is one of the most common agents given for lymphodepletion before CD19 chimeric antigen receptor T cells, but its optimal therapeutic intensity is unknown. Using data from a multicenter consortium, we estimated fludarabine exposure (area under the curve [AUC]) using a population pharmacokinetic (PK) model in 199 adult patients with aggressive B-cell non-Hodgkin lymphomas who received commercial axicabtagene ciloleucel (Axi-cel). We evaluated the association of estimated fludarabine AUC with key outcomes, aiming to find an AUC that optimized efficacy and tolerability.

Crop Disease Identification by Fusing Multiscale Convolution and Vision Transformer.

With the development of smart agriculture, deep learning is playing an increasingly important role in crop disease recognition. The existing crop disease recognition models are mainly based on convolutional neural networks (CNN). Although traditional CNN models have excellent performance in modeling local relationships, it is difficult to extract global features.

Exploring Research on the Construction and Application of Knowledge Graphs for Aircraft Fault Diagnosis.

Fault diagnosis is crucial for repairing aircraft and ensuring their proper functioning. However, with the higher complexity of aircraft, some traditional diagnosis methods that rely on experience are becoming less effective. Therefore, this paper explores the construction and application of an aircraft fault knowledge graph to improve the efficiency of fault diagnosis for maintenance engineers.

Combining cell-free RNA with cell-free DNA in liquid biopsy for hematologic and solid tumors.

Current use of liquid biopsy is based on cell-free DNA (cfDNA) and the evaluation of mutations or methylation pattern. However, expressed RNA can capture mutations, changes in expression levels due to methylation, and provide information on cell of origin, growth, and proliferation status. We developed an approach to isolate cell-free total nucleic acid (cfDNA) and used targeted next generation sequencing to sequence cell-free RNA (cfRNA) and cfDNA as new approach in liquid biopsy.

The impact of immunosuppressive agents on immune checkpoint inhibitor efficacy in patients with advanced melanoma: A real-world, multicenter, retrospective study.

Background: Immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) are often managed via immunosuppressive agents (ISAs); however, their impact on ICI efficacy is not well studied. The impact of the use of ISAs on ICI efficacy in patients with advanced melanoma was therefore investigated.

Methods: This is a real-world, multicenter, retrospective cohort study of patients with advanced melanoma who received ICIs (n = 370).

Green winner determination method based on environmental performance and minimum adjustment consensus in 4PL transportation service procurement.

Due to the intensified environmental protection consciousness of enterprises and consumers, the green winner determination (GWD) considering environmental performance becomes very important for the 4PL transportation service procurement. In this paper, a new GWD method is studied, which considers different types of attributes including those related to environmental performance and the consensus reaching process (CRP). To characterize multiple types of attributes, linguistic terms, interval numbers, and crisp numbers are combined.

Anti-spike antibody response to the COVID vaccine in lymphoma patients.

Patients with hematologic malignancies have poor outcomes from COVID infection and are less likely to mount an antibody response after COVID infection. This is a retrospective study of adult lymphoma patients who received the COVID vaccine between 12/1/2020 and 11/30/2021. The primary endpoint was a positive anti-COVID spike protein antibody level following the primary COVID vaccination series.