Since the use of highly active antiretroviral therapy (HAART) to treat HIV, physicians have seen an improvement in the prognosis for patients with AIDS-related lymphomas.
Researchers from the National Cancer Institute (NCI) have now identified a biological basis for this change. The results of the new study, reported in the June 15, 2003, issue of the journal "Blood"*, suggest that the use of HAART has caused a shift in the majority of AIDS-related lymphomas to a type that usually responds well to chemotherapy.
AIDS-related lymphomas now make up the cause of death for up to 20 percent of patients with HIV. Although the prognosis is generally poorer than for those patients with similar cancers who do not have HIV, survival has improved significantly since the use of HAART.
The authors of the study analyzed lymphoma samples from 39 patients with HIV who were being treated with a chemotherapy regimen known as dose-adjusted EPOCH. They found high levels of proteins that indicated these cancers were particularly well-suited to respond to the treatment.
"Our findings suggest that the improved immune function associated with HAART has led to a shift in which cells are most likely to give rise to lymphoma. The type of AIDS-related lymphoma most common today responds much more readily to treatment than lymphoma from the pre-HAART era," said Wyndham Wilson, M.D., head of the Lymphoma Clinical Research Section of NCI's Experimental Transplantation and Immunology Branch, who is the lead author on the study.
Dose-adjusted EPOCH, which is made up of the drugs etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin, recently was shown by the same research team to be a highly effective treatment for AIDS-related lymphomas. In the current study, 29 patients (74 percent) achieved complete response to the lymphoma treatment, and five (13 percent) achieved partial response.
The researchers analyzed proteins associated with tumor growth, drug resistance, and the origin of the cancer in patients' lymphoma samples, and found that the majority of samples had high levels of proteins associated with rapid growth. High levels of proteins associated with multidrug resistance have been found in other studies. Dose-adjusted EPOCH is effective against cancers with both of these characteristics.
Previous research has shown that the type of cell that gives rise to lymphoma plays an important role in determining how well the cancer will respond to standard chemotherapy. Wilson's research team found that lymphomas in the current study were likely to have originated from cells that correspond to a favorable prognosis. This is in contrast to AIDS-related lymphomas from the era before HAART, which were much more likely to arise from the cell type correlated with a poor clinical outcome.
A second important finding of this study is that antiretroviral therapy can be safely suspended during lymphoma treatment. Although physicians have traditionally considered HAART necessary to prevent uncontrolled HIV replication and loss of immune function during chemotherapy, drug interactions can have adverse effects on the lymphoma treatment. This study found that temporarily discontinuing HAART did not worsen AIDS progression and allowed for high overall survival. Once lymphoma treatment was complete, viral control and immune recovery were again achieved.
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* Little, RF, et. al. Highly effective treatment of acquired immunodeficiency syndrome related lymphoma with dose-adjusted EPOCH: Impact of antiretroviral therapy suspension and tumor biology. "Blood" 2003; 101:4653-4659.
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