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Scientists Unlocking Lymphoma's Secrets

Follicular lymphoma is a killer, but findings offer new hope

WEDNESDAY, Nov. 17, 2004 (HealthDayNews) -- For years, doctors have puzzled over the fact that some patients with follicular lymphoma succumb to the deadly blood cancer within a few years, while others survive for decades, even though their tumor cells look the same under the microscope.

Now, researchers believe they've solved that mystery.

Genetic differences -- not in lymphoma cells, but in immune cells surrounding the tumor -- may determine how aggressive a particular case of follicular lymphoma turns out to be, they said.

The finding should help doctors provide patients with more accurate prognoses, and may also open the door to new treatments for a disease for which there is currently no cure.

"What everyone is working on right now, and what holds a lot of promise, are therapies based on manipulating the immune system," said lead researcher Dr. Louis M. Staudt, of the National Cancer Institute's Center for Cancer Research.

He said studies have already shown that treatment with immune-based anti-cancer vaccines "does result in remission in some patients."

The latest findings appear in the Nov. 18 issue of the New England Journal of Medicine.

Follicular lymphoma is a type of white blood cell cancer from the non-Hodgkin's lymphoma family of lymph node malignancies. Follicular lymphomas involve the uncontrolled growth of a specific type of immune white blood cell, called B lymphocytes. The disease makes up about one-fifth of all non-Hodgkin's lymphomas, with an incidence rate of about six cases per 100,000 persons per year, experts say.

Unfortunately, research into controlling follicular lymphoma has yet to achieve the success seen in other blood cancers, Staudt said.

"In essence, chemotherapy isn't able to prolong the survival of these patients," he said. "It's given to them, but it's not curative."

Still, oncologists have long noticed that some patients with follicular lymphoma die with two or three years of diagnosis, while others live with the disease for upwards of 20 years or more.

Genetic comparisons of aggressive vs. less aggressive cancers have so far turned up no major differences, so Staudt and his team decided to investigate the genetics of immune cells living in the immediate vicinity of the lymphoma.

Examining tissue biopsies from 191 patients, the researchers found that "it was the [genetic] character of the immune cells that was dictating whether you had a very slow-growing form of follicular lymphoma, or a more rapid form," Staudt said.

He said the finding makes sense because, in very rare cases, follicular lymphoma will simply disappear on its own. "In oncology, that's taken as evidence that a tumor can be successfully fought off by the immune system," he said.

The next step is to discover how the immune cells of patients with slower cancers are keeping follicular lymphoma at bay. According to Staudt, one theory holds that "the immune cells may simply be fighting off the cancer" within the lymph node.

Another hypothesis holds that neighboring immune cells somehow allow cancer cells to survive -- but only within the confines of the lymph node. "Every time the cell tries to leave the lymph node, it doesn't have those neighbors anymore, so it doesn't proliferate, it dies," Staudt said.

Whatever the reasons, the findings should make it easier for doctors "to classify [each] case as a good, or bad, prognosis case," said the author of a journal commentary on the study, Ralf Küppers of the University of Duisberg-Essen, in Germany.

"This may help in the decision of how to treat the patient," he added. "For example, if a patient has a bad prognosis, one might decide for a more aggressive treatment, because standard treatment may have little chance to increase the life expectancy of the patient."

A more accurate prognosis should also help clarify the future for worried patients, Staudt said. "Imagine that you have a lump -- of course you're very concerned, and it comes back [from biopsy] with a diagnosis of follicular lymphoma. But in the next sentence, your doctor says, 'But the median survival of patients with your type of follicular lymphoma is between 10.8 and 13.6 years.' That's going to give you a whole different outlook on your disease."

According to Küppers, the finding "also points to a direction for potential novel treatment strategies."

"Other non-tumor cells in the tissue influence the survival and proliferation of the follicular lymphoma cells," he explained. "Thus, if one could interfere with survival signals supplied by other cells in the lymph nodes to the lymphoma cells, one might impair the growth of the tumor."

Staudt said research into a follicular cancer vaccine is already under way, using lymphoma cell antigens to "prime" nearby immune cells to attack the malignancy.

"In some patients, it clearly makes their tumors go away," he said. "To me, that's another indication that this tumor is one of the cancers that can respond to the immune system."

More information

For more details on follicular lymphoma and other lymphomas, visit the Leukemia & Lymphoma Society.

SOURCES: Louis M. Staudt, M.D., Ph.D., chief, Lymphoid Malignancies Section, Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Md.; Ralf Küppers, Ph.D., Institute for Cell Biology (Tumor Research), University of Duisburg-Essen, Essen, Germany; Nov. 18, 2004, New England Journal of Medicine
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