Biology and management of primary effusion lymphoma

Abstract

Primary effusion lymphoma (PEL) is a rare B-cell malignancy that most often occurs in immunocompromised patients, such as HIV-infected individuals and patients receiving organ transplantation. The main characteristic of PEL is neoplastic effusions in body cavities without detectable tumor masses. The onset of the disease is associated with latent infection of human herpes virus 8/Kaposi sarcoma-associated herpes virus, and the normal counterpart of tumor cells is B cells with plasmablastic differentiation. A condition of immunodeficiency and a usual absence of CD20 expression lead to the expectation of the lack of efficacy of anti-CD20 monoclonal antibody; clinical outcomes of the disease remain extremely poor, with an overall survival at 1 year of ∼30%. Although recent progress in antiretroviral therapy has improved outcomes of HIV-infected patients, its benefit is still limited in patients with PEL. Furthermore, the usual high expression of programmed death ligand 1 in tumor cells, one of the most important immune-checkpoint molecules, results in the immune escape of tumor cells from the host immune defense, which could be the underlying mechanism of poor treatment efficacy. Molecular-targeted therapies for the activating pathways in PEL, including NF-κB, JAK/STAT, and phosphatidylinositol 3-kinase/AKT, have emerged to treat this intractable disease. A combination of immunological recovery from immune deficiency, overcoming the immune escape, and the development of more effective drugs will be vital for improving the outcomes of PEL patients in the future.

Primary effusion lymphoma in human immune deficiency (HIV)‐negative non‐organ transplant immunocompetent patients

“…The molecular drivers for PEL are still unknown; nonetheless, emerging therapies such as targeted therapy for activating pathways in PEL such as mammalian target of rapamycin (mTOR) are being investigated, 38 immunomodulatory drugs such as lenalidomide are in clinical trial. 39 In summary, we here presented a very rare case of PEL from an immunocompetent, HIV-negative patient, and reviewed the literature, with only 27 similar cases have been previously reported. It is important to recognize that although the majority of PEL patients are immunocompromised, complete pathologic workup is still necessary to rule out PEL in immunocompetent patients presenting with a malignant effusion cytology.…”

“…There was a slight survival advantage between patients who received chemotherapy (n = 17, 22 months) and those who received pleurodesis, thoracentesis, or supportive care only (n = 9, 13.8 months); however, no statistical significance was achieved. The molecular drivers for PEL are still unknown; nonetheless, emerging therapies such as targeted therapy for activating pathways in PEL such as mammalian target of rapamycin (mTOR) are being investigated, immunomodulatory drugs such as lenalidomide are in clinical trial …”

Narciclasine, an isocarbostyril alkaloid, has preferential activity against primary effusion lymphoma

“…PEL accounts for approximately 4% of all HIV-related non-Hodgkin lymphoma and is universally associated with KSHV infection 16 . The median overall survival of PEL is only 4.8 months, indicating an urgent need to identify new therapeutic options for this disease 17 .…”

Lenalidomide in Combination with Arsenic Trioxide: an Effective Therapy for Primary Effusion Lymphoma

“…Primary effusion lymphoma (PEL) is an aggressive non-Hodgkin B-Cell lymphoma (NHL) secondary to Kaposi sarcoma herpes virus (KSHV) [1,2]. This virus originally described as acquired immunodeficiency syndrome (AIDS)-associated Kaposi sarcoma [3], was later referred to as human herpesvirus type 8 (HHV-8) [1,2,4]. PEL accounts for around 4% of human immunodeficiency virus (HIV)-associated NHL and less than 1% of non-HIV-related lymphomas [5].…”

“…It typically occurs in middle-aged immunocompromised patients, infected either with HIV or recipients of solid-organ transplants, and in elderly patients in HHV-8 endemic areas [ 6 , 7 , 8 , 9 , 10 ]. Clinically, PEL typically presents as body cavity lymphoma with malignant lymphomatous effusions invading peritoneal, pleural, and/or pericardial cavities [ 2 , 11 ]. Extra-cavitary PEL with solid tumor masses is less frequent, and when present, it involves organs adjacent to the cavitary space, regional lymph nodes, and gastrointestinal tract among others [ 12 , 13 ].…”