Publications by authors named "Constantine Logothetis"

5 Publications

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Incidence and Management of Effusions Before and After CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy in Large B Cell Lymphoma.

Transplant Cell Ther 2021 Mar 27;27(3):242.e1-242.e6. Epub 2020 Dec 27.

Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida; Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, Florida. Electronic address:

In patients with lymphoma, third-space fluid accumulations may develop or worsen during cytokine release syndrome (CRS) associated with chimeric antigen receptor (CAR) T cell therapy. Pre-existing symptomatic pleural effusions were excluded by the ZUMA-1 trial of axicabtagene ciloleucel for large B cell lymphoma (LBCL) and variants. The incidence and management of effusions during CAR T cell therapy for LBCL are unknown. We performed a single-center retrospective study evaluating 148 patients receiving CD19-directed CAR T cell therapy for LBCL between May 2015 and September 2019. We retrospectively identified patients who had radiographic pleural, pericardial, or peritoneal effusions that were present prior to the time of CAR T infusion (pre-CAR T) or that newly developed during the first 30 days after CAR T-cell infusion (post-CAR T). Of 148 patients, 19 patients had a pre-CAR T effusion, 17 patients without pre-existing effusion developed a new infusion after CAR T, and 112 patients had no effusions. Comparing pre-CAR T effusions to new effusions post-CAR T, pre-CAR T effusions were more often malignant (84% versus 12%), persistent beyond 30 days (95% versus 18%), and required interventional drainage after CAR T infusion (79% versus 0%). Compared to patients with no effusion, patients with pre-CAR T therapy effusions had a higher frequency of high-risk baseline characteristics, such as bulky disease and high International Prognostic Index. Similarly, patients with pre-CAR T therapy effusions had a higher rate of toxicity with grade 3 or higher CRS occurring in 32% of patients. On multivariate analysis adjusting for age, Eastern Cooperative Oncology Group status, bulky disease, albumin, and lactate dehydrogenase, a pre-CAR T therapy effusion was associated with reduced overall survival (hazard ratio, 2.34; 95% confidence interval, 1.09 to 5.03; P = .03). Moreover, there was higher non-relapse mortality (11% versus 1%; P = .005). Post-CAR T effusions were not associated with significant difference in survival. Effusions commonly complicate CAR T cell therapy for lymphoma. Malignant effusions that occur prior to CAR T therapy are frequently persistent and require therapeutic intervention, and patients have a higher rate of toxicity and death. Effusions that newly occur after CAR T therapy can generally be managed medically and tend not to persist.
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http://dx.doi.org/10.1016/j.jtct.2020.12.025DOI Listing
March 2021

Cerebral Venous Thrombosis in the Setting of Malignancy: Case Report and Review of the Literature.

Case Rep Hematol 2020 17;2020:8849252. Epub 2020 Sep 17.

Division of Hospital Medicine Department of Internal Medicine, University of New Mexico School of Medicine, University of New Mexico, MSC10 5550, Albuquerque, NM 87131, USA.

Cerebral venous thrombosis (CVT) is a rare condition that can be difficult to diagnose due to its vague and nonspecific symptoms. It is even more unusual to identify CVT in association with malignancy. Given the rarity of this disease, treatment and management of CVT in the setting of malignancy is not well defined. This case report and review of the literature addresses the epidemiology, pathophysiology, and medical treatment for malignancy-related CVT.
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http://dx.doi.org/10.1155/2020/8849252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519989PMC
September 2020

Exosomal secretion of a psychosis-altered miRNA that regulates glutamate receptor expression is affected by antipsychotics.

Neuropsychopharmacology 2020 03 27;45(4):656-665. Epub 2019 Nov 27.

Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.

The ability of small secretory microvesicles known as exosomes to influence neuronal and glial function via their microRNA (miRNA) cargo has positioned them as a novel and effective method of cell-to-cell communication. However, little is known about the role of exosome-secreted miRNAs in the regulation of glutamate receptor gene expression and their relevance for schizophrenia (SCZ) and bipolar disorder (BD). Using mature miRNA profiling and quantitative real-time PCR (qRT-PCR) in the orbitofrontal cortex (OFC) of SCZ (N = 29; 20 male and 9 female), BD (N = 26; 12 male and 14 female), and unaffected control (N = 25; 21 male and 4 female) subjects, we uncovered that miR-223, an exosome-secreted miRNA that targets glutamate receptors, was increased at the mature miRNA level in the OFC of SCZ and BD patients with positive history of psychosis at the time of death and was inversely associated with deficits in the expression of its targets glutamate ionotropic receptor NMDA-type subunit 2B (GRIN2B) and glutamate ionotropic receptor AMPA-type subunit 2 (GRIA2). Furthermore, changes in miR-223 levels in the OFC were positively and negatively correlated with inflammatory and GABAergic gene expression, respectively. Moreover, miR-223 was found to be enriched in astrocytes and secreted via exosomes, and antipsychotics were shown to control its cellular and exosomal localization in a cell-specific manner. Furthermore, addition of astrocytic exosomes in neuronal cultures resulted in a significant increase in miR-223 expression and a notable reduction in Grin2b and Gria2 mRNA levels, which was strongly inversely associated with miR-223 expression. Lastly, inhibition of astrocytic miR-223 abrogated the exosomal-mediated reduction in neuronal Grin2b expression. Taken together, our results demonstrate that the exosomal secretion of a psychosis-altered and glial-enriched miRNA that controls neuronal gene expression is regulated by antipsychotics.
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http://dx.doi.org/10.1038/s41386-019-0579-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021900PMC
March 2020

Tumoral Calcinosis of the Neck in a Patient with Systemic Sclerosis.

Cureus 2018 Nov 13;10(11):e3585. Epub 2018 Nov 13.

Internal Medicine, University of New Mexico School of Medicine, Albuquerque, USA.

Tumoral calcinosis (TC) is rare in patients with systemic sclerosis but is associated with morbidity. Paraspinal TC may cause severe pain and potentially devastating neurological deficits. Surgical decompression by removing the TC masses and applying surgical techniques to support the spine have provided substantial relief of the symptoms in the majority of cases. However, death has occurred in the immediate postoperative period and can even occur after several months. Current indications for surgery include intractable neck pain and, most importantly, the development of neurological deficits. We present a patient with systemic sclerosis and symptomatic paraspinal TC in the neck treated conservatively for two years. This case report illustrates conditions permitting the sustained conservative treatment of paraspinal TC in systemic sclerosis patients.
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http://dx.doi.org/10.7759/cureus.3585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334890PMC
November 2018