Human herpesvirus-8-positive primary effusion lymphoma in HIV-negative patients: Single institution case series with a multidisciplinary characterization
Authors: Rossi, Giovanni; Cozzi, Ilaria; Della Starza, Irene; De Novi, Lucia Anna; De Propris, Maria Stefania; Gaeta, Aurelia; Petrucci, Luigi; Pulsoni, Alessandro; Pulvirenti, Federica; Ascoli, Valeria
BACKGROUND Primary effusion lymphoma (PEL) is a very rare non-Hodgkin lymphoma caused by human herpesvirus-8 (HHV8) that grows in liquid phase within body cavities. The diagnosis of PEL is based on cytology but requires confirmatory ancillary tests. PEL occurs mainly in association with HIV infection. This study describes 9 cases of PEL in HIV-negative patients and compares their characteristics with 10 HIV-associated cases of PEL diagnosed at a single institution in Italy between 1995 and 2019. METHODS Clinical records were reviewed for demographic data, comorbidities, laboratory abnormalities, and outcome. PEL samples were evaluated for cytomorphology, immunophenotype, immunoglobulin (IG)/T cell receptor (TR) rearrangements, and HHV8 and Epstein-Barr virus (EBV) viral loads in effusion supernatants. RESULTS HIV-unrelated PEL occurred in 8 elderly patients (7 men, 1 woman) and 1 young adult with primary antibody deficiency. Cytology revealed HHV8-positive lymphoma cells lacking B/T cell antigens and exhibiting 2 cell patterns (polymorphous or monotonous).IGwas clonally rearranged in all cases; aberrantTRGoccurred in 2 cases. Effusion supernatants had more than 10(6)HHV8 DNA copies per mL and variable loads of EBV DNA. Compared with HIV-associated PEL, the HIV-negative cohort was characterized by older age, less frequent association with Kaposi sarcoma and/or multicentric Castleman disease, comparable but less abnormal laboratory parameters, and a nonsignificant survival benefit. PEL cases with low apoptosis were associated with better prognosis. CONCLUSION To the best of our knowledge, our case series of HIV-unrelated PEL is the largest thus far, expands the spectrum of cytological findings, and supports the need for a multidisciplinary approach in the diagnostic workup.
The effects of beta(1)and beta(1+2)adrenergic receptor blockade on the exercise-induced mobilization and ex vivo expansion of virus-specific T cells: implications for cellular therapy and the anti-viral immune effects of exercise
CELL STRESS & CHAPERONES
Authors: Kunz, Hawley E.; Agha, Nadia H.; Hussain, Maryam; LaVoy, Emily C.; Smith, Kyle A.; Mylabathula, Preteesh; Diak, Douglass; Baker, Forrest L.; O'Connor, Daniel P.; Bond, Richard A.; Katsanis, Emmanuel; Bollard, Catherine M.; Simpson, Richard J.
The adoptive transfer of donor-derived virus-specific T cells (VSTs) is an effective treatment for infections following allogeneic hematopoietic cell transplantation. Acute exercise mobilizes effector lymphocytes and VSTs to the circulation and augments the ex vivo manufacture of VSTs. This study determined if beta(2)adrenergic receptor (AR) signaling precipitated the VST response to acute exercise. Healthy participants (n = 12) completed 30 min of steady-state cycling exercise after ingesting a placebo, a beta(1 + 2)AR antagonist (nadolol) or a beta(1)AR antagonist (bisoprolol). Circulating VSTs to cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (AdV) antigens were enumerated before and after exercise, and peripheral blood mononuclear cells were cultured with viral peptides for 8 days to expand multi-VSTs. Compared with placebo, nadolol blunted the exercise-induced mobilization of CMV-VSTs (Delta VSTs/100,000 CD3(+)T cells = 93 +/- 104 vs. 22 +/- 91 for placebo and nadolol, respectively;p = 0.036), while bisoprolol did not, despite both drugs evoking similar reductions in exercising heart rate and blood pressure. Circulating AdV and EBV VSTs (VSTs/mL blood) only increased after exercise with placebo. Although not significant, nadolol partially mitigated exercise-induced increases in multi-VST expansion, particularly in participants that demonstrated an exercise-induced increase in VST expansion. We conclude that exercise-induced enhancements in VST mobilization and expansion are at least partially beta(2)AR mediated, thus highlighting a role for the beta(2)AR in targeted therapy for the augmentation of VST immune cell therapeutics in the allogeneic adoptive transfer setting. Moreover, long-term regular exercise may provide additional viral protection in the host through frequent beta(2)AR-dependent mobilization and redistribution of VSTs cumulated with each bout of exercise.