Genetics

Scientists are making great progress in understanding how changes in DNA can cause normal lymphocytes to develop into lymphoma cells. This is providing insight into why these cells may grow too rapidly, live too long, and not develop into mature cells that take part in normal immune reactions. Once this is understood, drugs may be developed that block this process.

Progress in understanding DNA changes in lymphoma has already provided improved and highly sensitive tests for detecting this disease. Such tests can identify lymphoma cells based on gene changes such as translocations or rearrangements. For example, the polymerase chain reaction (PCR) test can detect one lymphoma cell among a million normal cells. Aside from being used to detect and classify lymphomas, the test is useful in helping determine how completely the lymphoma has been destroyed by treatment and whether a relapse is likely.

One of the more important breakthroughs in recent years has been the development of DNA microarrays. These are tests of gene patterns in a tumor's DNA that may help spot abnormal genes in the tumor. This may lead to new classifications of these diseases. The tests may also be useful in identifying those patients who may need early treatment with high-dose chemotherapy and stem cell transplants. The usefulness and reliability of these tests is now being studied.

Treatment

Much of the research being done on non-Hodgkin lymphoma is focused on looking at new and better ways to treat this disease.

Chemotherapy

New chemotherapy drugs are being studied in clinical trials. Others are studying new ways to combine drugs using different doses or different sequences of drugs.

Newer, non-traditional drugs such as bortezomib (Velcade) and thalidomide (Thalomid) have shown some promise in treating certain leukemias. These and similar drugs are now being studied.

Biological Therapy

Lymphoma cells contain certain chemicals on their surface. Monoclonal antibodies that recognize these substances can be targeted to destroy the lymphoma cells while causing little damage to normal body tissues. This treatment strategy has already proven effective. Several such drugs, including rituximab, are already available and are discussed in the section, "How Is Non-Hodgkin Lymphoma Treated?"

Rituximab is often given for a limited amount of time during treatment. Because it has few side effects, new studies are testing its long-term use to see if it helps prevent lymphomas from coming back. The use of rituximab in this type of "maintenance therapy" is still considered experimental by most doctors.

Because of the success of rituximab and its radioactive counterparts (ibritumomab and tositumomab), new monoclonal antibodies are being developed. Using them in combination with chemotherapy is also being tested in clinical trials.

Bone Marrow and Peripheral Blood Stem Cell Transplants

Researchers continue to improve bone marrow and peripheral blood stem cell transplant methods, including new ways to collect these cells before the transplant.

Autologous (taken from the patient rather than another person) transplants have the risk of reintroducing lymphoma cells back into the patient after treatment. Researchers are testing new and improved ways to remove the last traces of lymphoma from these stem cells before they are returned to the patient. Some of the new monoclonal antibodies developed for treating lymphoma may help remove these remaining cells.

A lot of research is focusing on eliminating graft-versus-host disease in allogeneic (donor) transplants. This work revolves around altering the transplanted T-cells so that they won't react with the recipient's normal cells but still kill the lymphoma cells.

Lymphoma Vaccines

Doctors have known for some time that people's immune systems may help fight their cancer. In rare instances, these people's immune systems have rejected their cancers, and they have been cured. Scientists are now trying to develop ways to encourage this immune reaction by the use of vaccines.

Unlike vaccines against infections like measles or mumps, these vaccines are designed to help treat, not prevent, lymphomas (therapeutic vaccines). With cancer vaccines, the goal is to create an immune reaction in patients who have very early disease or in patients whose disease is in remission. One possible advantage of these types of treatments is that they seem to have very limited side effects. So far, there have been a few successes with this approach, and it is a major area of research in lymphoma treatment. At this time lymphoma vaccines are only available in clinical trials.

MyVax^TM, BiovaxID^TM, and FavId^TM are vaccines based on the unique genetic makeup of a patient's B-cell non-Hodgkin lymphoma (NHL). The vaccines use a unique protein (part of an antibody called an idiotype) taken from each patient's own lymphoma cells. This is combined with a substance called an adjuvant that helps stimulate an immune reaction when the combination is injected into the patient. These vaccines are now in late-stage clinical trials testing their effectiveness against follicular lymphomas. Their use against other types of lymphomas is also being tested.