Opportunistic infection and immunologic function in patients with human immunodeficiency virus-associated non-Hodgkin's lymphoma treated with chemotherapy

Background: The incidence of systemic non-Hodgkin’s lymphoma (NHL) is higher in the population infected with human immunodeficiency virus (HIV) than in the uninfected population. Standard treatment for this cancer involves the administration of systemic chemotherapy. Purpose: Our objective was to determine the relative risk (RR) of opportunistic infection and the relative change in immunologic function in a cohort of patients who had HIV-associated NHL and who were treated with combination chemotherapy and to compare them with those in a matched cohort of control subjects who had advanced HIV infection but no signs of NHL. Methods: We performed a case‐control study in which the clinical course of each patient with HIV-associated NHL (n = 43; case subjects) treated with infusional cyclophosphamide, doxorubicin, and etoposide was compared with that of two patients with HIV infection but without lymphoma who were matched for CD4 lymphocyte count and prior opportunistic infection (n = 86; control subjects). The patients’ medical records were reviewed for all information related to acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections, survival, cause of death, and lymphocyte subset analyses. Univariate and multivariate analyses were performed to determine whether any of a number of confounding factors (e.g., age, sex, CD4 count, prior opportunistic infection, and prior antiretroviral therapy) could have influenced the risk of developing a first infectious event (defined as opportunistic infection or nonlymphoma death). All P values resulted from two-sided statistical tests. Results: In the univariate analysis, a significantly greater risk for a first event was associated with being a case subject (RR = 1.8; 95% confidence intervals [CI] = 1.1-3.0; P<.05), having a low CD4 count (<100/µL) (RR = 3.1; 95% CI = 1.8-5.4; P<.0001), being female (RR = 1.7; 95% CI = 1.1-3.3; P<.05), having prior Pneumocystis carinii pneumonia (RR = 3.5; 95% CI = 1.9-6.3; P<.0001), having any prior opportunistic infection (RR = 3.6; 95% CI = 2.1-6.4; P<.0001), and having prior antiretroviral therapy (RR = 1.9; 95% CI = 1.1-3.3; P<.05). In the multivariate analysis, however, being a case subject (RR = 2.1; 95% CI = 1.2-3.6; P<.01), having a low CD4 count (RR = 2.1; 95% CI = 1.2-3.9; P<.05), and being female (RR = 3.0; 95% CI = 1.8-5.6; P<.001) were the only characteristics associated with an increased risk of a first event. When the mean CD4 lymphocyte count at approximately 1 year was compared with that at baseline, there was a significantly greater decrease in the CD4 count among case subjects than among control subjects (mean decrease ± standard deviation [SD] = 99/µL ± 138/µL versus 29/µL ± 100/µL; P = .03). Conclusions: Treatment of patients who have HIV-associated NHL with a non-steroid-containing chemotherapy regimen was associated with a significant and sustained reduction in the CD4 lymphocyte count and a twofold increase in the risk of developing opportunistic infection. Implications: Oncologists and other physicians who treat patients with HIVassociated NHL should be familiar with the prophylaxis, recognition, and management of opportunistic infection. In addition, there is a need to identify effective strategies for the amelioration of chemotherapy-induced immunosuppression in this population. [J Natl Cancer Inst 1997;89:301-7] The incidence of non-Hodgkin’s lymphoma (NHL) in patients with the human immunodeficiency virus (HIV) infection is increasing; approximately 5000 of such cases were diagnosed in