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Gene Chip Predicts Lymphoma Survival

Can tell who -- and who won't -- benefit from chemotherapy

WEDNESDAY, June 19, 2002 (HealthDayNews) -- A gene screening test that finds molecular signatures of blood cancer can give doctors a fix on which patients are likely to do well in treatment -- and which will probably die despite it.

The test hunts for genes that are switched on in a family of cancers called diffuse large-B-cell lymphomas, frequently deadly malignancies that strike white blood cells. The virulence of the cancer is spelled out in its genetic tableau. By identifying which of these instructions are active, doctors can predict five-year survival after drug treatment for the disease, says a new study.

Survival rates for the quarter of patients with the most favorable gene profile neared 75 percent. But for the quarter with the worst molecular makeup, the five-year survival rate was just 15 percent.

For those people, doctors may have difficult advice to deliver, says the National Cancer Institute's Dr. Louis Staudt, a co-author of the study.

"That's such a low rate that one would wonder if it would be wise for them to skip [chemotherapy] and try something different," such as a bone marrow transplant or an experimental therapy.

A report on the study appears in tomorrow's issue of the New England Journal of Medicine.

Lymphoma affects roughly 50,000 men and women a year in this country. Of those, about 16,000 are so-called diffuse large-B-cell forms of the disease.

In recent years, Staudt and his colleagues have been working on a device they call the "Lymphochip." This postage-stamp sized piece of glass contains a computer array that can recognize some 18,000 genes with known or suspected roles in cancer and normal immune system activity.

In earlier work with the chip, the researchers found two large groups of lymphoma patients whose gene activity profile helped determine the aggressiveness of their cancer.

In the latest study, which analyzed blood samples from 240 people with B-cell lymphomas, the researchers added a third category to the first two groups. They also identified several sub-groups within the larger clusters that influenced prognosis.

In all, the scientists found 17 genes that predict survival from the disease after chemotherapy. Two of the gene signatures reflect how well the body's immune response handles the cancer.

The Lymphochip is still only a research tool. However, Staudt predicts that all cancer diagnoses will ultimately be made with the aid of such devices. Doctors will then treat tumors with tailored drug regimens that target their particular genetic and molecular essence.

Alan Kinniburgh, vice president for research at the Leukemia & Lymphoma Society, says patients might not be enthusiastic about learning their prognosis on conventional therapy is so bleak. However, when the ability to treat these people catches up with the new diagnostic tools, that should change.

"Patients do not want to be taking medicines and being treated in ways that will not help them," says Kinniburgh, an expert in molecular diagnostics. "And I think physicians do not want to put patients on a therapeutic regimen that doesn't work."

Gene-reading devices such as the Lymphochip will help doctors recognize subsets of patients who demand more aggressive treatment.

"As we go forward and patients with the aggressive form [of lymphoma] are treated aggressively, we'll see if they do better," he says. Studies over the next five to six years will tell whether such an approach will work, he adds.

What To Do

For more on the effort to profile lymphoma, visit the National Institutes of Health. For more on blood cancers, try the Leukemia & Lymphoma Society.

SOURCES: Louis Staudt, M.D., Ph.D., senior investigator, National Cancer Institute, Bethesda, Md.; Alan Kinniburgh, Ph.D., vice president, research, Leukemia & Lymphoma Society, White Plains, N.Y.; June 20, 2002, New England Journal of Medicine
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