Elevated expression of activation induced cytidine deaminase in peripheral blood mononuclear cells precedes AIDS-NHL diagnosis.

Non-Hodgkin's B cell lymphoma (NHL) is a common cancer in HIV infection. Many NHL are thought to result from errors in class switch recombination and/or somatic hypermutation, processes that occur in germinal center B cells, and require the activity of activation induced cytidine deaminase (AID). Since NHL is a common cancer in HIV infection, and expression of AID could contribute to the development of NHL, we hypothesized that AID expression would be elevated in those who went on to develop AIDS-associated NHL (AIDS-NHL). AID mRNA levels were measured by TaqMan RT-PCR in peripheral blood mononuclear cells, obtained prior to AIDS-NHL diagnosis, from 16 HIV-infected subjects who developed AIDS-NHL, and from control subjects (AIDS but no NHL, and HIV-negative subjects). PBMC AID expression was markedly elevated in those who developed AIDS-NHL, when compared to AIDS and HIV-negative controls. Additionally, AID expression was seen to differ depending on NHL subtype, with the highest levels of expression seen in those who developed Burkitt's lymphoma.

Quantitative measurement of telomerase activity in lymphadenopathy: correlation with histologic features and human immunodeficiency virus-1 infection.

Telomerase is a ribonucleoprotein that uses its internal RNA component as a template for synthesis of telomeric DNA on the ends of chromosomes after each round of cell division. It is expressed in approximately 90% of all human cancers tested to date, as well as in most immortal cell lines. Recently, telomerase activity was detected in normal proliferating lymphoid tissue and in non-Hodgkin's lymphomas (NHLs) by use of the telomeric repeat amplification protocol assay, a qualitative measure of telomerase activity. In this study, we modified the assay to measure quantitatively the telomerase activity in lymph node biopsy specimens obtained from patients with lymphadenopathy. The lymph nodes either contained benign reactive changes, were involved by NHL of B-cell lineage, or were involved by Hodgkin's disease. Telomerase activity was detected in all of our samples, benign as well as malignant. The levels of activity were unaffected by the patient's human immunodeficiency virus-1 status. Although the specimens involved by NHLs showed a range in telomerase activity from low to high, the levels did not correlate strictly with the histologic grade according to the Working Formulation. All of the cases of Hodgkin's disease also expressed telomerase activity, and the levels were similar regardless of histologic subtype. Our results showed that telomerase activity was expressed in both benign and malignant lymphoproliferative processes.

Age and serum lactate dehydrogenase level are independent prognostic factors in human immunodeficiency virus-related non-Hodgkin's lymphomas: a single-institute study of 96 patients.

PURPOSE: The role of classical pragnostic factors (ie, age, performance status [PS], stage, extranodal involvement, and serum lactate dehydrogenase [LDH] level) included in the International Index for diffuse large-cell non-Hodgkin's lymphoma (NHL) of the general population is presently unknown in the setting of human immunodeficiency virus (HIV). To assess the prognostic value of these factors in HIV-related NHL, we reviewed the cohort of patients with HIV-related NHL diagnosed and treated with combination chemotherapy (CT) at our institution. PATIENTS AND METHODS: Ninety-six patients with systemic HIV-related NHL diagnosed and treated with combination CT regimens between September 1987 and December 1993 at the Centro di Riferimento Oncologico, Aviano, Italy, were studied. All clinical and laboratory data were evaluated by univariate and multivariate analyses, using overall survival as the end point. RESULTS: Complete remission (CR) occurred in 48% of patients; the overall median survival and disease-free survival times were 7 and 13 months, respectively. Among the classical and HIV-related prognostic factors, the following had a statistically significant influence on survival: PS > or = 2, elevated LDH level, age greater than 40 years, a CD4 cell count less than 100/microL, active opportunistic infections at diagnosis of NHL, and B symptoms. Multivariate analyses showed that only age, serum LDH level, and CD4 cell count were independent predictors of shortened survival. The increased hazard for patients greater than 40 years of age was 1.6 (95% confidence interval [CI], 1.2 to 2.3), for patients with increased LDH it was 1.8 (95% CI, 1.01 to 3.1), and for patients with a CD4 cell count less than 100/microL it was 1.7 (95% CI, 1.01 to 2.9). CONCLUSIONS: Our study shows that in addition to HIV-related prognostic factors, ie, CD4 cell count less than 100/microL, classical prognostic factors such as age and serum LDH level are independent prognostic factors and should be included in the design of future clinical trials of HIV-related NHL.