AIDS-related Central Nervous System Lymphoma Research Articles

Primary lymphoma of the central nervous system: epidemiology, pathology and current approaches to diagnosis, prognosis and treatment

An overview of the current approaches to the management of patients with primary central nervous system lymphoma (PCNSL) is provided. Although accumulating evidence demonstrates that PCNSL is a curable type of brain tumor, in many cases establishing the diagnosis and overcoming chemotherapeutic resistance remain significant obstacles. The issue of treatment-related neurotoxicity is also a central consideration in treatment planning. The introduction of highly active antiretroviral therapy has had a major impact on this disease in that the incidence of AIDS-related central nervous system lymphoma, once highly prevalent in the 1980s and 1990s, has now virtually disappeared. However, the problem of diagnostic delays secondary to steroid effects, radiation-induced neurotoxicity and methotrexate resistance represent unique and important problems in this disease. The use of anti-CD20 antibody in this disease represents the first application of biologically based targeted therapies for PCNSL; however, the overall impact of this modality in brain lymphoma awaits further evaluation in ongoing studies The application of proteomic as well as gene expression technologies is yielding insights into PCNSL pathogenesis, in particular specific oncogenic pathways, which may be exploited to develop new therapies.

Intracranial hematopoiesis in a patient with aids-related central nervous system lymphoma and severe pancytopenia

The case here reported reflects the difficulty in diagnosing meningeal extramedullary hematopoiesis (EMH), which clinically appeared concomitantly with primary cerebral lymphoma and occurred in a patient with HIV infection and severe pancytopenia. Pancytopenia secondary to HIV infection could be hypothesized as a predisposing factor for the ectopic development of hematopoietic tissue outside the bone marrow. Although rare, intracranial EMH should always be considered in the differential diagnosis of headache and other endocranial hypertension symptoms in patients with chronic bone marrow dysfunction.

AIDS-related central nervous system lymphomas.

To evaluate combined radio-chemotherapy in patients with AIDS-related lymphomatous meningitis (LM) or primary central nervous system lymphoma (PCNSL). Eighteen men and 2 women with AIDS had cytologically documented LM. Fifteen patients had systemic non-Hodgkin's lymphoma with LM and 5 patients had PCNSL with CSF dissemination. Standardized pre-treatment evaluations included contrast cranial MRI, placement of an intraventricular reservoir, contrast spine MRI, ophthalmologic evaluation and 111Indium-DTPA CSF flow studies. Regions of bulky or symptomatic disease were treated with limited-field irradiation. Concurrent systemic chemotherapy was administered in 18 patients. All patients were scheduled to receive intraventricular methotrexate (MTX) according to a concentration x time (C x T) drug schedule. In cytologic or clinical failures, patients were treated with salvage therapy using intraventricular ara-C and in a similar manner, patients were treated with intraventricular thio-TEPA following cytologic relapse or clinical failure intraventricular following intraventricular ara-C. Sixty-seven patients (63 men; 4 women) with PCNSL underwent a standardized pre-treatment evaluation as in patients with LM and were treated according to 3 schedules. In the first group (n = 15), comfort care was offered. In the second group (n = 45), whole brain radiotherapy was administered. In the third group (n = 7), patients were treated with combined radio- and chemotherapy using systemic procarbazine, CCNU and vincristine (PCV-3). The third group was selected based on a Karnofsky performance status > or =60, no evidence of disseminated PCNSL, a CD4 count >200, no concurrent opportunistic infection and a patient's desire for aggressive therapy. In the LM patient group, 16 patients were evaluable as 4 patients subsequently withdrew consent for treatment. Median time to tumor progression/survival were as follows: not-treated (n = 4) 12 days/ month; treated non-responding (n = 6) 30 days/2 months; and treated responding (n = 10) 130 days/6 months. In the PCNSL patient group, median range survival were as follows: comfort care (n = 15) 1.5/0.5-3 months; whole brain radiotherapy (n = 45) 4/1.5-5 months; and combined radio-chemotherapy (n = 7) 13/10-18 months. Combined radio- and chemotherapy is appropriate for a small subset of patients with AIDS and either LM or PCNSL. This approach results in meaningful palliation not strikingly dissimilar from that seen in non-AIDS patients.

Multiplex PCR for diagnosis of AIDS-related central nervous system lymphoma and toxoplasmosis.

A nested multiplex PCR assay was designed for the simultaneous detection of Epstein-Barr virus and Toxoplasma gondii DNA from the cerebrospinal fluid of AIDS patients. T. gondii DNA was detected in 8 of 8 patients with Toxoplasma encephalitis and in 0 of 6 patients without toxoplasmosis, and Epstein-Barr virus DNA was found in 9 of 14 patients with central nervous system lymphoma and in 2 of 38 patients without disease.

A comparison of survival of patients treated for AIDS-related central nervous system lymphoma with and without tissue diagnosis

This is a retrospective review of the treatment outcome of radiation therapy (RT) in acquired immune-deficiency syndrome (AIDS) patients with presumed primary central nervous system (CNS) non-Hodgkin's lymphoma (NHL), with and without tissue verification. Twenty-seven patients with AIDS-related CNS NHL were treated between 1986 and 1992. They were divided into two groups. Group 1 consisted of nine patients with a positive histology for NHL. They were treated with dexamethasone (DXM) and whole brain RT. Group 2 consisted of 18 patients who, because of unique circumstances, were treated without histologic confirmation of NHL. Rapid clinical and/or radiologic response to DXM and whole-brain RT was interpreted as NHL. For group 1, the response rate was 87.5%, mean survival 6.1 months, and median survival 4.5 months. For group 2, the response rate was 72.2%, mean survival 5.2 months, and median survival 4.5 months. The overall response rate was 76.9%, mean survival 5.8 months, and median survival 4.5 months. In instances where a tissue diagnosis cannot be established, a positive response to an empiric trial of DXM and RT to 20 Gy may constitute presumptive evidence of NHL.