The shift in AIDS-related lymphomas toward chemotherapy-responsive tumors is probably due to retention of immune system function during treatment with highly active antiretroviral therapy, according to an article in the June 15th issue of Blood.

In the current study, investigators evaluated 39 HIV-infected patients who had recently been diagnosed with lymphoma and were being treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH).

Protein expression analyses evaluated presence and concentrations of proteins associated with tumor growth, drug resistance, and origin of the tumor in samples from the HIV-infected patients and a matched group of lymphoma patients without HIV infection. The AIDS-related lymphoma samples had lower levels of bcl-2 and higher expression of CD10, which is consistent with a germinal center origin and good prognosis. Interestingly, the AIDS-related samples were also more likely to be highly proliferative and to express p53, features that are usually consistent with poor response to standard chemotherapy.

Investigators concluded that the success of the 5-drug chemotherapy regimen was at least in part due to the highly proliferative nature of the AIDS-related lymphomas. When the researchers reviewed clinical records, they found that p53 overexpression in the AIDS-related cases was not associated with poor outcome; they hypothesized that this finding reflects a different pathogenesis than that for non-AIDS-related lymphomas with high levels of p53 expression.

In the current study, 29 of the 39 patients with AIDS-related lymphoma (74 percent) achieved complete response to chemotherapy, and 5 (13 percent) achieved partial response. At 53 months median follow-up, disease-free survival was 92 percent and overall survival was 60 percent.

"Our findings suggest that the improved immune function associated with highly active antiretroviral therapy has led to a shift in which cells are most likely to give rise to lymphoma [from post-germinal center to germinal center origin]. The type of AIDS-related lymphoma most common today responds much more readily to treatment than lymphoma from the pre-highly active antiretroviral therapy era," said Wyndham Wilson, M.D., of the National Institutes of Health and the senior study author.

A second important finding of this study is that antiretroviral therapy can be safely suspended during lymphoma treatment. Although physicians have traditionally
considered the retroviral therapy necessary to prevent uncontrolled HIV replication and loss of immune function during chemotherapy, drug interactions can have adverse effects on lymphoma treatment. This study found that temporarily discontinuing antiretroviral therapy did not worsen AIDS progression and allowed for high overall survival. After lymphoma treatment was complete, viral control and immune recovery were again achieved.