Non-Hodgkin’s lymphomas (NHLs) are a very heterogeneous group of cancers that develop in the lymph nodes located throughout the body. There are over 25 subtypes of NHL.
Most occur relatively infrequently, and the two most common (diffuse large B-cell and follicular lymphomas) account for over 50% of cases. Primary effusion lymphoma (also called body cavity lymphoma) is quite rare, representing less than 2% of NHL cases. It is considered an aggressive lymphoma.
Unlike most types of NHL, the cause of primary effusion lymphoma is actually known. Human herpes virus type 8 (HHV-8, also called Kaposi’s sarcoma-associated herpes virus) leads to the development of primary effusion lymphoma. In fact, primary effusion lymphoma was not identified as a distinct subtype of NHL until the discovery of HHV-8 in 1994. 90% of these lymphoma cells are also infected with the Epstein-Barr virus.
Almost all patients with primary effusion lymphoma are HIV-positive. Case reports of those not HIV-positive commonly describe patients who were immunosuppressed for other reasons, such as post-organ transplant. HIV-related lymphoma is not unusual: it occurs in 5 to 20% of HIV-positive patients and is considered an AIDS-defining illness.
However, most HIV-related lymphomas are of the diffuse large B-cell or Burkitt’s type. Hence, even in the setting of HIV-related NHL, primary effusion lymphoma is rare.
Signs and Symptoms
Primary effusion lymphoma manifests in the pleural, pericardial, or peritoneal cavities in the body and lacks identifiable lymphoma masses. The pleural cavities are the spaces between the lungs and the lining that covers them, called the pleura. The pericardial cavity is the space between the heart itself and its lining, the pericardium.
These spaces are usually not really spaces at all, with the organ linings serving a protective role. The peritoneal cavity contains all the lower abdominal organs. In primary effusion lymphoma, there is an abnormal accumulation of fluid in these spaces as a result of the lymphoma cells. This fluid build-up causes lung, heart, or gastrointestinal organ dysfunction, depending upon the areas affected.
Patients may present with shortness of breath, chest pain, and/or abdominal distension. Swollen lymph nodes are not generally present in this type of NHL.
Diagnosis and Staging
Because there aren’t any discreet lymphoma masses to biopsy, the diagnosis of primary effusion lymphoma is confirmed by sampling the fluid accumulated in the pleural, pericardial, or peritoneal spaces. A pathologist then examines the fluid for the presence of lymphoma cells. Cells must be positive for HHV-8 for a diagnosis of primary effusion lymphoma. Many other types of NHL can present with effusions and should be ruled-out prior to considering treatment options.
Once the diagnosis of primary effusion lymphoma is established, work-up should include CT scans of the chest, abdomen, and pelvis, a complete blood count, and serum chemistries (including a lactate dehydrogenase level). A bone marrow biopsy should be performed if the patient has low blood counts.
In addition, an echocardiogram or MUGA scan to evaluate heart function should be done in any patient opting for treatment, due to the risk of chemotherapy-related heart failure. This is particularly important in patients with a pericardial effusion, in which heart function may already be diminished. Primary effusion lymphoma is not staged in the traditional sense, and is, by definition, advanced, stage IV disease.
The prognosis of primary effusion lymphoma is very poor, as it is usually resistant to currently available chemotherapy drugs. Most patients only survive an average of six months from the time of diagnosis, and only one-third of patients live a year.
First-Line Treatment of Primary Effusion Lymphoma
Because there are so few cases of primary effusion lymphoma, there are no prospective, randomized clinical trials to guide treatment decisions. Most of the treatment data available are based upon published case series. In addition, most oncologists are unfamiliar with treating this form of NHL, and patients should consider referral to a large cancer center for treatment in a clinical trial.
Most case reports of patients with primary effusion lymphoma have modeled treatment after diffuse large B-cell lymphoma, which is the most common type of aggressive NHL. First-line treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has been reported to result in a response rate of 40 to 50%.
Patients who are HIV-positive should be initiated or continued on anti-viral therapy for their HIV. The improvement in the immune system seen with anti-HIV therapies seems to be important for the treatment of patients with HIV-related lymphomas, including primary effusion lymphoma. There are even case reports of patients achieving a complete response to anti-HIV therapy alone.
Treatment of Recurrent/Refractory Primary Effusion Lymphoma
There is no standard treatment for recurrent primary effusion lymphoma. Investigational treatments are the best option for patients but should be administered in the setting of a clinical trial, at a cancer center experienced at treating HIV-related lymphomas. Some drugs that have shown success in case reports include the anti-viral drug cidofovir and bortezomib, a drug that disrupts cellular homeostasis. Patients with a poor performance status may opt for supportive care.
Hematopoietic stem cell transplant (also called bone marrow transplant) is the standard of care in patients with a good performance status who have recurrent or refractory aggressive NHL. The most common procedure is an autologous transplant, in which the patient’s own blood stem cells are harvested, then re-infused following very-high-dose chemotherapy.
Allogeneic bone marrow transplants (blood stem cells from another person, usually a sibling) are also used as treatment for relapsed NHL. Some clinicians extrapolate results in common aggressive NHLs to those of primary effusion lymphoma patients and utilize bone marrow transplant as a treatment for relapsed disease. There is no evidence that bone marrow transplant is a cure for primary effusion lymphoma, and it remains an investigational treatment.
Supportive Care Issues
Supportive care of the patient with primary effusion lymphoma centers around organ function preservation and symptom management. As discussed, patients with fluid in the pleural or pericardial cavities may experience shortness of breath, difficulty breathing, and chest pain.
This can be temporarily alleviated with the use of diuretics to pull the fluid away from the lungs or heart, as well as draining the fluid with a needle inserted into the pleural or pericardial space. Patients with abdominal involvement of primary effusion lymphoma can also have the accumulated fluid drained with a procedure called a paracentesis, to alleviate the discomfort of abdominal distention.
HIV-positive patients who receive chemotherapy for HIV-related lymphomas (including primary effusion lymphoma) should receive G-CSF support. G-CSF is a white blood cell growth factor that helps to ameliorate the low white blood cell counts that are seen following each treatment with chemotherapy.
Anti-HIV drugs also have numerous drug interactions. Patients should inform their oncology health care providers of all the anti-HIV drugs they are taking, to assure that no toxic interactions will occur once chemotherapy is initiated.