Exacerbations of Persistent Neurotoxicity following Axicabtagene Ciloleucel in a Patient with Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Case Report.

Introduction: Neurological toxicity following chimeric antigen receptor T-cell infusion, termed immune cell-associated neurotoxicity syndrome (ICANS), is a common and limiting factor in the expansion of this promising treatment modality. While refractory cases of ICANS have been reported in clinical trials, there is limited description of these presentations and their associated treatment. The use of predictive biomarkers and risk stratification tools offer a means of identifying patients with higher likelihood of developing ICANS; however, their discriminatory sensitivity has been shown to vary depending on disease type. Case Presentation: In this case report, we present the clinical course of a patient with diffuse large B-cell lymphoma treated with axicabtagene ciloleucel who developed a nonsinusoidal pattern of severe neurotoxicity refractory to steroid treatment, and we evaluate the predictive value of commonly used biomarkers and risk scores in assessing the likelihood of her presentation. Conclusion: In assessing the efficacy of these scores in the context of our patient's pattern of severe neurotoxicity exacerbations, we aim to provide valuable clinical insight to better manage refractory ICANS and ultimately improve patient outcomes.

Prognosis and Treatment Outcomes of Bone Metastasis in Gallbladder Adenocarcinoma: A SEER-Based Study.

BACKGROUND: Gallbladder carcinoma (GBC) is a rare, aggressive malignancy comprising 0.5% of gastrointestinal cancers. It has poor survival outcomes due to its insidious onset, lack of standardized screening, and limited therapies. Advanced-stage diagnosis with liver, lymph node, and peritoneal metastasis is common, while bone metastasis is rare. The knowledge on bone metastasis in GBC is limited to case reports and small series, and its clinical significance is largely unexplored. METHODS: The study extracted the demographic and clinical variables of patients with metastatic (M1) gallbladder adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database between 2011 and 2020. Descriptive statistics were used to analyze the demographic characteristics. The multivariate Cox regression analysis was used to calculate the hazard ratio. The overall survival (OS) was assessed using the Kaplan-Meier method, and the log-rank test was utilized to compare the survival between the groups. RESULTS: A total of 2724 patients were included in the study. A total of 69% of the patients were female, and the median age was 68 (range 24-90+). A total of 7.4% of the patients had bone metastasis on diagnosis. The multivariate Cox analysis identified bone metastasis as an independent mortality risk factor in metastatic GBC (HR 1.50, p < 0.001). The patients were divided into two age groups: a younger age group (18-74 years) and an older age group (75+ years). In the younger group, the median OS with and without bone metastasis was 3 and 5 months, respectively (p < 0.0001). In the older age group, there was no significant difference in the OS between the patients with and without bone metastasis (p = 0.35). In the younger group who were treated with chemotherapy, the patients with bone metastasis had a significantly worse OS (median OS 5 months vs. 8 months, p < 0.0001). In the untreated group, the patients with bone metastasis in the younger age group had a significantly worse OS (median OS 1 month vs. 2 months, p = 0.014). In the patients with bone metastasis, those who did not receive chemotherapy had a significantly worse OS than those who were treated with chemotherapy in both age groups (younger age group: median OS 1 month vs. 5 months, p < 0.0001 and older age group: median OS 1 month vs. 5 months, p = 0.041). CONCLUSIONS: Our findings suggest that the presence of bone metastasis in gallbladder adenocarcinoma is an independent prognostic factor associated with unfavorable survival outcomes in the younger age group (18-74 years). However, in the older age group (75+ years), the presence of bone metastasis did not impact the survival. Treatment with chemotherapy was associated with extended survival in all patients. Thus, early detection and aggressive management of bone metastasis, including the consideration of chemotherapy, may be crucial in improving the OS and quality of life for individuals with gallbladder adenocarcinoma.

Cellular Cancer Immunotherapy Development and Manufacturing in the Clinic.

The transfusion of naturally derived or modified cellular therapies, referred to as adoptive cell therapy (ACT), has demonstrated clinical efficacy in the treatment of hematologic malignancies and metastatic melanoma. In addition, cellular vaccination, such as dendritic cell-based cancer vaccines, continues to be actively explored. The manufacturing of these therapies presents a considerable challenge to expanding the use of ACT as a viable treatment modality, particularly at academic production facilities. Furthermore, the expanding commercial interest in ACT presents new opportunities as well as strategic challenges for the future vision of cellular manufacturing in academic centers. Current trends in the production of ACT at tertiary care centers and prospects for improved manufacturing practices that will foster further clinical benefit are reviewed herein.