Patients with cancer are at risk for thrombotic complications due to a hypercoagulable state. However, the benefit of prophylactic anticoagulation is unclear in many subsets of these patients. For the first episode of acute thromboembolic disease (VTE) in patients with active cancer, anticoagulant therapy is administered for at least three to six months. Herein, we present a 31-year-old female with active, recurrent stage IIIa classical Hodgkin lymphoma (CHL) (nodular sclerosis), previously treated for proximal upper extremity deep vein thrombosis (DVT), presenting for evaluation of shortness of breath and eventually diagnosed with bilateral pulmonary embolism (PE) secondary to a right atrial thrombus. The patient was successfully treated with surgical resection of the thrombus. With this case report, we hope to encourage physicians to use prophylactic indefinite anticoagulation in patients with active cancer and previous DVT, including patients with upper extremity DVT.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a lethal emergency. Delays in diagnosis and treatment are detrimental to the health of patients. Classical clinical manifestations of HLH include fever, cytopenia, liver dysfunction, central nervous system involvement, and coagulopathy.
METHODS: We report seven cases of secondary HLH in adults diagnosed from a total of 1200 bone marrow aspiration and trephine biopsy (BMAT) examinations in our center, with various presentations and underlying triggers including infection, malignancy, and autoimmune disease.
RESULTS: HLH can present with non-specific signs and symptoms.
CONCLUSIONS: Early recognition of HLH is crucial to enable the commencement of therapy as early as possible to prevent mortality resulting from multi-organ failure.

Off-the-shelf (OTS) adoptive T cell therapies have many benefits such as immediate availability, improved access and reduced cost, but face the major challenges of graft-vs-host disease (GVHD) and graft rejection, mediated by alloreactive T cells present in the graft and host, respectively. We have developed a platform for OTS T cell therapies by using Epstein-Bar virus (EBV)-specific T cells (EBVSTs) expressing a chimeric antigen receptor (CAR) targeting CD30. Allogeneic EBVSTs have not caused GVHD in several clinical trials, while the CD30.CAR, that is effective for the treatment of lymphoma, can also target alloreactive T cells that upregulate CD30 on activation. Although EBVSTs express high levels of CD30, they were protected from fratricide in cis, by the CD30.CAR. Hence, they could proliferate extensively and maintained function both through their native EBV-specific T cell receptor and the CD30.CAR. The CD30.CAR enabled EBVSTs to persist in co-cultures with naive and primed alloreactive T cells and eliminate activated natural killer cells that can also be alloreactive. In conclusion, we show that CD30.CAR EBVSTs have the potential to be an effective OTS therapy against CD30+ tumors and, if successful, could then be used as a platform to target other tumor antigens.

Background Early treatment of intracranial lesions in the emergency department is crucial, but it can be challenging to differentiate between them. This differentiation is essential because the treatment of each type of lesion is different. Cerebral computed tomography perfusion (CTP) imaging can help visualize the vascularity of brain lesions and provide absolute quantification of physiological parameters. Compared to magnetic resonance imaging, CTP has several advantages, such as simplicity, wide availability, and reproducibility. Purpose This study aimed to assess the effectiveness of Hounsfield units (HU) in measuring the density of hypercellular lesions and the ability of CTP to quantify hemodynamics in distinguishing intracranial space-occupying lesions. Methods A retrospective study was conducted from March 2016 to March 2022. All patients underwent CTP and CT scans, and relative cerebral blood volume (rCBV) and HU were obtained for intracranial lesions. Results We included a total of 244 patients in our study. This group consisted of 87 (35.7%) individuals with glioblastomas (GBs), 48 (19.7%) with primary central nervous system lymphoma (PCNSL), 45 (18.4%) with metastases (METs), and 64 (26.2) with abscesses. Our study showed that the HUs for METs were higher than those for GB (S 57.4% and E 88.5%). In addition, rCBV values for PCNSL and abscesses were lower than those for GB and METs. The HU in PCNSL was higher than those in abscesses (S 94.1% and E 96.6%). Conclusion PCT parameters provide valuable information for diagnosing brain lesions. A comprehensive assessment improves accuracy. Combining rCBV and HU enhances diagnostic accuracy, making it a valuable tool for distinguishing between lesions. PCT\'s widespread availability allows for the use of both anatomical and functional information with high spatial resolution for diagnosing and managing brain tumor patients.

Advancements in lymphoma treatment have increased the number of long-term survivors who may experience late effects such as impaired sexual function and testosterone deficiency. The aim of this review was to determine the prevalence of testosterone deficiency and sexual dysfunction among male lymphoma survivors; and associations between the two. A systematic search identified 20 articles for inclusion. The prevalence of low total testosterone was 0%-50 %, with mean values within reference levels, and for luteinizing hormone above reference levels in 0%-80 %. Four studies included SHBG and free testosterone, with mixed results. Compromised sexual health was found in 23%-61 %. Overall, total testosterone and sexual health were associated. The risk of bias (ROBINS-E and RoB 2) was high/very high, leading to low/very low overall confidence in the bulk of evidence (GRADE). Longitudinal studies evaluating biologically active testosterone and sexual health are needed, to develop evidence based standard procedures for follow-up of sexual health.

Introduction Cancer exerts a substantial influence on the body\'s metabolism through varied mechanisms, instigating a metabolic reprogramming that maintains the unchecked growth and survival of cancer cells, consequently perturbing diverse metabolic parameters. The introduction of positron emission tomography-computed tomography (PET/CT), delivering detailed insights into both metabolic and morphological aspects, has brought about a revolutionary shift in modern cancer detection. Exploring the potential connection between PET-CT metabolic features and the metabolic parameters of liver enzymes in an individual can unveil novel avenues for cancer diagnosis and prognosis. Materials and methods This study conducted a retrospective analysis of patient records from our institution, covering the period from January 2021 to September 2023, focusing on individuals with various malignancies. The data included information on gender, age, clinical history, and liver serum parameters, which were compiled into tables. Additionally, inflammatory indicators such as ALT (alanine transaminase), ALP (alkaline phosphatase), total protein (TP), ALT/AST ratio, and SUVmax were collected and plotted. The study used Pearson correlation analysis to assess the relationship between each inflammatory variable and SUV (max) as determined by PET-CT. Results In breast cancer, there was a statistically significant positive correlation (R2=0.0651) between serum ALP levels and SUVmax as determined by regression analysis. Hodgkin lymphoma, on the other hand, showed a statistically significant negative correlation between the ALT-to-AST ratio (ALT/AST) and SUVmax (r = -0.45, R2 = 0.204). In non-Hodgkin lymphoma patients, total protein (TP) was negatively correlated with SUVmax (R2=-0.081, r= -0.28), while in lung cancer patients, there was a significant positive correlation with regression correlation coefficients (R2 = 0.026, 0.024, 0.024, and 0.018 for ALT/AST, TP, ALP, albumin, and ALT, respectively). Conclusion Aligning with these results, it can be a recent addition to acknowledge that both the tumor metabolic parameter (SUVmax) and the levels of liver serum enzymes exhibit a potential for predicting patient prognosis in various cancers.

BACKGROUND: Adoptive cell therapy using genetically modified T cells to express chimeric antigen receptors (CAR-T) has shown encouraging results, particularly in certain blood cancers. Nevertheless, over 40% of B cell malignancy patients experience a relapse after CAR-T therapy, likely due to inadequate persistence of the modified T cells in the body. IL15, known for its pro-survival and proliferative properties, has been suggested for incorporation into the fourth generation of CAR-T cells to enhance their persistence. However, the potential systemic toxicity associated with this cytokine warrants further evaluation.
METHODS: We analyzed the persistence, antitumor efficacy and potential toxicity of anti-mouse CD19 CAR-T cells which express a membrane-bound IL15-IL15Rα chimeric protein (CD19/mbIL15q CAR-T), in BALB/c mice challenged with A20 tumor cells as well as in NSG mice.
RESULTS: Conventional CD19 CAR-T cells showed low persistence and poor efficacy in BALB/c mice treated with mild lymphodepletion regimens (total body irradiation (TBI) of 1 Gy). CD19/mbIL15q CAR-T exhibits prolonged persistence and enhanced in vivo efficacy, effectively eliminating established A20 B cell lymphoma. However, this CD19/mbIL15q CAR-T displays important long-term toxicities, with marked splenomegaly, weight loss, transaminase elevations, and significant inflammatory findings in some tissues. Mice survival is highly compromised after CD19/mbIL15q CAR-T cell transfer, particularly if a high TBI regimen is applied before CAR-T cell transfer.
CONCLUSIONS: Tethered IL15-IL15Rα augments the antitumor activity of CD19 CAR-T cells but displays long-term toxicity in immunocompetent mice. Inducible systems to regulate IL15-IL15Rα expression could be considered to control this toxicity.

BACKGROUND: Fludarabine in combination with cyclophosphamide (FC) is the standard lymphodepletion regimen for CAR T-cell therapy (CAR T). A national fludarabine shortage in 2022 necessitated the exploration of alternative regimens with many centers employing single-agent bendamustine as lymphodepletion despite a lack of clinical safety and efficacy data. To fill this gap in the literature, we evaluated the safety, efficacy, and expansion kinetics of bendamustine as lymphodepletion prior to axicabtagene ciloleucel (axi-cel) therapy.
METHODS: 84 consecutive patients with relapsed or refractory large B-cell lymphoma treated with axi-cel and managed with a uniform toxicity management plan at Stanford University were studied. 27 patients received alternative lymphodepletion with bendamustine while 57 received FC.
RESULTS: Best complete response rates were similar (73.7% for FC and 74% for bendamustine, p=0.28) and there was no significant difference in 12-month progression-free survival or overall survival estimates (p=0.17 and p=0.62, respectively). The frequency of high-grade cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was similar in both the cohorts. Bendamustine cohort experienced lower proportions of hematological toxicities and antibiotic use for neutropenic fever. Immune reconstitution, as measured by quantitative assessment of cellular immunity, was better in bendamustine cohort as compared with FC cohort. CAR T expansion as measured by peak expansion and area under the curve for expansion was comparable between cohorts.
CONCLUSIONS: Bendamustine is a safe and effective alternative lymphodepletion conditioning for axi-cel with lower early hematological toxicity and favorable immune reconstitution.

UNASSIGNED: Aims to provide an overview of the contemporary epidemiology of malignant orbital tumors by analyzing population-based incidence patterns across various regions worldwide.
UNASSIGNED: In this article, we retrieved orbital malignancy data from the MEDLINE database and analyzed the incidence and prevalence of orbital malignancies worldwide. We performed the literature search by searching on the Mesh terms for malignant orbital tumors (\"orbital\", \"tumor\", \"lymphoma\", \"malignant\", \"cancer\", \"incidence\", and \"epidemiology\"). All included studies were published between 1993 and 2023 and were written in English.
UNASSIGNED: Ocular or ophthalmic lymphoma most frequently occurred in the orbit, with a prevalence ranging from 47% to 54%. The incidence of malignant orbital tumors was increasing in the USA (2.0 per million (1981-1993), Netherlands (0.86 (1981-1985) to 2.49 (2001-2005) per million) and South Korea (0.3-0.8 per million (1999-2016)), respectively. Ophthalmic lymphoma which includes orbit lymphoma was increasing in Canada (0.17-1.47 per million (1992-2010)), Denmark (0.86 per million (1981-1985) to 2.49 per million (2001-2005)), respectively.
UNASSIGNED: The predominant primary malignant orbital tumor in adults was lymphoma. Ocular or ophthalmic lymphoma most frequently occured in the orbit. The limited data available suggested an increasing trend in the incidence of malignant orbital tumors in each country included, which were mainly attributed to the increase in lymphoma. Generally, incidence rates were found to increase with advancing age, with no difference between males and females.

Chimeric antigen receptor (CAR)-T cell-based immunotherapy has emerged as a path-breaking strategy for certain hematological malignancies. Assessment of the response to CAR-T therapy using quantitative imaging techniques such as positron emission tomography/computed tomography (PET/CT) has been broadly investigated. However, the definitive role of PET/CT in CAR-T therapy remains to be established. [18F]FDG PET/CT has demonstrated high sensitivity and specificity for differentiating patients with a partial and complete response after CAR-T therapy in lymphoma. The early therapeutic response and immune-related adverse effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome can also be detected on [18F]FDG PET images. In otherwise asymptomatic lymphoma patients with partial response following CAR-T therapy, the only positive findings could be abnormal PET/CT results. In multiple myeloma, a negative [18F]FDG PET/CT after receiving B-cell maturation antigen-directed CAR-T therapy has been associated with a favorable prognosis. In leukemia, [18F]FDG PET/CT can detect extramedullary metastases and treatment responses after therapy. Hence, PET/CT is a valuable imaging tool for patients undergoing CAR-T therapy for pretreatment evaluation, monitoring treatment response, assessing safety, and guiding therapeutic strategies. Developing guidelines with standardized cutoff values for various PET parameters and tumor cell-specific tracers may improve the efficacy and safety of CAR-T therapy.