DNA Expression may Help Guide Treatment Options for Lymphoma

DNA Expression may Help Guide Treatment Options for Lymphoma

According to a recent article published in The New England Journal of Medicine, DNA expression profiles may help predict survival following standard chemotherapy for patients with diffuse large B-cell lymphoma. In turn, this information could assist physicians and patients in making more individualized treatment decisions for patients with large B-cell lymphoma.

Non-Hodgkin’s lymphoma is a cancer of the lymph tissue, which is part of the body’s immune system. Lymph tissue is present in lymph nodes, lymph vessels, blood and bone marrow. It is also present in organs, such as the thymus, tonsils and spleen. The main cells in the lymph system are lymphocytes, of which there are two types: B and T-cells. Each of these cells has a very specific function in aiding the body to fight infection. The large majority of NHL cases involves cancer of the B-lymphocytes and characterized by the excessive accumulation of these atypical cells. This results in overcrowding of blood and lymph tissue, suppressing the formation and function of blood and immune cells that are normally present. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further decrease in the ability of the body to fight infection. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL in adults.

Currently, the most common therapy used for DLBCL is a chemotherapy combination consisting of cyclophosphamide (Cytoxan®), doxorubicin (Adriamycin®), Oncovin® (vincristine), and prednisone, often called CHOP. Although the majority of DLBCL patients initially respond to treatment with CHOP, a large percentage of these patients ultimately experience a return of their cancer. Therefore, researchers have been evaluating disease characteristics of patients with DLBCL in an attempt to identify which variables predict for better or worse outcomes, which could lead to individualized treatment decisions. Physicians have been relying on the International Prognostic Index (IPI) to predict the prognosis of patients with DLBCL. The IPI involves the patient’s age, patient ability to perform daily tasks, number of sites the cancer has spread, lactate dehydrogenase level and cancer stage. However, the reliability and accuracy of IPI in determining a patient’s prognosis has been questioned.

Researchers for the lymphoma/leukemia molecular profiling project recently analyzed biopsy specimens of 236 patients who had been diagnosed with DLBCL. The specimens were obtained and frozen prior to any therapy. Patients were treated with an anthracycline-based regimen, CHOP being the most common, so researchers could compare gene profiles of the specimen to treatment outcome. The researchers used a gene chip, also known as a microarray of 12,000 genes, to determine differences in expression of genes in different specimens. Researchers found three genetic patterns that were strongly associated with survival. Within these three patterns, researchers narrowed down 17 key genes that had the most difference in expression between patients who had good outcomes following treatment compared to patients who had poor outcomes following treatment. These 17 genes were used in a mathematical formula to place patients in one of four prognostic groups. The five-year survival of patients in these groups was 73%, 71%, 34% and 15%. When accuracy of prognosis was compared between IPI and gene expression profiling, gene expression was more accurate.

This trial indicates that gene profiling may better predict response to standard, anthracycline-based therapies in patients with DLBCL. Patients who are stratified into the poor-prognosis group following therapy according to gene profiling may wish to pursue more aggressive or investigational therapies in order to improve outcomes. The future direction of gene profiling will include all types of cancer and will help to individualize treatment regimens to provide optimal results. Patients with DLBCL may wish to speak with their physician about the risks and benefits of participation in a clinical trial further evaluating gene profiling or other promising screening measure. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (cancer.gov) and www.eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients.

Reference: Rosenwald A, Wright G, Chan W, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma.

The New England Journal of Medicine. 2002;346:1937-1947.

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