Cancer Physician Sets Sights on Lymphoma

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MADISON - Medical research isn't always about attempting the most radical treatment to add years to a cancer sufferer's life. Sometimes, the research lies in knowing what not to do, and how to take it slow.

There are more than 35 different types of non-Hodgkin's lymphoma. Some are curable, others incurable. According to the National Cancer Institute, there will be an estimated 66,120 new cases and 19.160 deaths from NHL in the United States in 2008.


Non-Hodgkin's lymphoma, a cancer that can occur at any age, begins in the cells of the immune system when a lymphocyte - usually a B-cell – becomes abnormal and begins to replaicte. The abnormal cells don't protect the body from infections or other diseases.

Dr. Brad Kahl, director of the UW Lymphoma Service, has made it his mission to tackle the worst of the worst with the development of novel treatments for lymphoma patients, helping to extend their quality of life by using relatively nontoxic approaches.

Kahl, as associate professor of medicine at the University of Wisconsin School of Medicine and Public Health, has worked as the principal investigator in a large national study involving the use of monoclonal antibodies to treat follicular lymphoma. He's also worked for the past eight years researching ways to improve treatment and survival rates for mantle cell lymphoma, the disease was known to have the worst survival rate of any of the lymphomas.

At the time, Kahl began working on improved treatment for patients with mantle cell lymphoma, the disease was known to have the worst survival rate of any of the lymphomas.


"People who came in with this just seemed doomed," he says.

After joining the UW faculty in 2000, Kahl's first study was successful in keeping patients in remission for an average of three years. Up to that point, patients in studies were kept alive for an average of three years.

Always looking for a better way, Kahl explored the use of a drug in a then-new class of proteasome inhibitors called bortezomib as a new means to kill cancer cells.

Kahl and his research team were very encouraged by the initial results after conducting a trial on relapse mantle cell patients. By using just borezomib, "we found that we could put almost 40 percent of the people back in remission," Kahl says.

From there, Kahl worked bortezomib into the front-line regimen he helped to develop in 2000 for treatment of newly diagnosed mantle cell lymphoma patients. UW has just completed a 30-patient study using the protocol, and more than 80 percent of patients are now in complete remission.


"So there's a suggestion that adding bortezomib is helping out," he says.

"Only time will tell, since the patients that are only three years into the study," Kahl says. Another one or two years are needed to fully understand the drug combination's impact.

He's also working on a national study to see if the UW results can be replicated on a much larger scale. Because mantle cell lymphoma is so rare, there is no standard treatment. No one really knows how best to treat mantle cells; therefore, treatment varies from place to place. Some treatments are very aggressive, with high doses of chemotherapy and a bone marrow transplant. UW takes a less aggressive approach, and the results have been quite positive.

Kahl tells one of his patients who was diagnosed with mantle cell lymphoma nearly four years ago. The patient sought a second opinion on treatment and was told he needed a bone marrow transplant. After Kahl expressed his concern to the patient about the effects of a bone marrow transplant on someone his age, the patient opted for the UW approach.

The patient has now been in remission for three years.


"He's doing beautifully," Kahl says with a big smile.

Kahl has gained a national reputation for his work in treating mantle cell lymphoma.


"A doctor out in the community maybe gets to see one patient with mantle cell every year," Kahl says. "But I see about one every month because I get a lot of referrals."


Since Kahl basically works with lymphoma 24/7, "I'm your guy," he says.

There's a trick to Kahl's other major area of study. It involves trying to fool a patient's immune system into helping fight the cancer. The study is the largest of its type in the world.

The study, of which Kahl is the lead investigator, compares two ways to administer the drug rituximab to fight follicular lymphoma. Half of the study's participants get one dosing strategy; the others get an alternative dosing strategy. Researchers look to see if one strategy provides better control over the lymphoma compared to the alternative strategy – and why it's working in some but not in others.

"We know that some patients just inherently are better programmed to respond to the antibody than others," says Kahl.


Some of the incurable types of lymphoma are very slow moving. Many people can live five, 10 or 15 years with their cancer.

"Well, if you could double that for everybody, maybe you'd have a whole group of patients who maybe die with their lymphoma rather than from their lymphoma," says Kahl. "So sometimes our goal is to try to figure out how to control the disease over long periods of time."

One of Kahl's patients was diagnosed with an incurable form of follicular lymphoma in 2000. By 2003, the slow-moving disease had begun to advance and looked like it was about to start causing problems. The patient was an eligible candidate for the large follicular lymphoma clinical trial using rituximab on which Kahl was working.

The patient, who receives a dose of the rituximab every three months, is still in complete remission after four and a half years.


"He's never needed a drop of chemotherapy for his cancer," Kahl says. "He has an outstanding quality-of-life. He just comes in, gets his treatment, and he looks as healthy as you or I. It's fun to see him every three months."


For patients diagnosed with an incurable lymphoma, Kahl's cutting-edge work is helping to extend their lives.

"We're trying to buy you a quality remission – one that lasts many, many years" he says. "So that by the time your disease comes back we'll be a lot smarter and we'll have some new options for you."

The Paul P. Carbone Comprehensive Cancer Center is the only institution of its kind in Wisconsin and one of only 38 designated by the National Cancer Institute, the lead federal agency for cancer research.