Mind & Body, September 2003

People With Blood Cancers Living Longer With New Therapies

September Is Leukemia, Lymphoma, And Myeloma Awareness Month

For blood cancers such as leukemia, lymphoma, and myeloma, chemotherapy has been the first line of defense until recently.

But new "molecularly targeted drugs" now are being hailed as precise and powerful weapons against cancers that are notoriously hard to treat. This new therapy attacks diseased cells directly and produces fewer side effects in the process.

"Unlike solid tumors, where surgery can be used to remove the tumor at an early stage and the patient might not be treated with anything else, we can't do that in blood cancers," explains Alan Kinniburgh, vice president of research at the Leukemia & Lymphoma Society (LLS).

"This was the first place chemotherapy was brought to bear and was successful," he says. "We're now at a point from where in 1960 about 4 percent survived longer than five years and now 85 percent do," Mr. Kinniburgh says.

To push beyond that 85 percent mark, researchers are pouring their energy into the development of these molecularly targeted drugs.

To heighten awareness of these developments, the LLS is observing September as Leukemia, Lymphoma, and Myeloma Awareness Month.

Leukemia refers to cancer of the bone marrow and blood cells. The two major categories are myelogenous and lymphocytic. Each of these can be further subdivided into acute (with a rapid onset and progression) and chronic (which develops and progresses more slowly).

Lymphomas are cancers that arise when lymphocytes - a type of white blood cell - become malignant. The two main types of lymphoma are Hodgkin's and non-Hodgkin's.

Myeloma affects the plasma cells (white blood cells found primarily in the bone marrow) and interferes with the body's immune system.

The cause of these cancers is uncertain, although they are thought to arise when a single cell with a genetic flaw starts replicating uncontrollably.

Targeted Drugs Equate With Success

While chemotherapy and other conventional treatments are still being used, the breakthroughs are coming as a result of molecularly targeted drug therapy.

"We've really spent a lot of time in the last couple of decades finding altered genes in cancer and now we're actually starting to develop molecular-targeted therapy to go after these altered genes," says Dr. Donald Small, of the Johns Hopkins University School of Medicine.

Specifically, scientists are looking at a class of frequently mutated genes called tyrosine kinases, which seem to be involved in many of the blood cancers, Dr. Small says.

Chronic myeloid leukemia, or CML, for instance, involves a genetic flaw in one of these genes that produces an abnormal protein. This triggers a signal that pushes cells to start reproducing.

A new drug, Gleevec®, goes inside the abnormal protein and commands it to stop sending the signal. Because the drug is so finely targeted, it has few side effects. Gleevec® now appears to be emerging as the drug of choice for CML, Dr. Small says.

Similarly promising research is taking place with acute myelogenous leukemia, or AML, a disease whose cure rate hovers at 20 percent to 30 percent.

"We really need new types of therapies and it may well be that, when chemo (chemotherapy) is combined with some of the targeted therapies, we could see a big impact," Dr. Small says.

Dr. Small and other researchers around the country are currently conducting trials with new molecularly targeted drugs that inhibit another tyrosine kinase gene, this one called FLT-3.

"There are patients who are having responses," Dr. Small reports.

In the case of AML, however, more than one drug will probably be needed to affect the multiple genes that are at fault.

"In chronic phase CML, it's probably a single gene, so it's a lot easier to target; you're basically hitting the whole disease," Dr. Small says. "In AML, there are probably three or four or more altered genes."

Other New Therapies Take Hold

Chemotherapy and radiation have both been around for half a century but can entail significant side effects.

"They kill growing cells and they kill the fastest first and that's fine, but it's kind of a blunt instrument when it's used," Mr. Kinniburgh says.

A newer approach is called immunotherapy, also targeted but not usually considered molecularly targeted. This involves developing antibodies that attack part of the cell surface, causing the cell to die. These are also called monoclonal antibodies.

And vaccines could help the patient's own immune system fight off blood cancer. No vaccines are yet approved, though some are in advanced clinical trials.

Many patients also need bone marrow transplants, which seek to replace a person's depleted healthy blood-forming cells with another person's.

"It's kind of a hybrid system of using someone else's immune system to reconstitute your own immune system after very vigorous chemo (chemotherapy) and/or radiation," Mr. Kinniburgh explains. "You just have to watch out for those cells attacking the body because there are differences. It kills patients every day."

Finally, there have been some recent reports that postmenopausal women who take aspirin regularly may have a lower incidence of acute leukemias.

Mostly, though, the world is moving in the direction of highly targeted treatments.

"Over time it will be more and more designer-type therapy," Dr. Small says. "Eventually, it may turn out that a patient comes in with a certain type of tumor, we take cells, see what genes are altered and pull compound A for this mutation and compound C for that one. It will be very, very specific and very much designer-type therapy."

Always consult your physician for more information.

Online Resources

(These links are provided for the education and convenience of our Neighbors. AAMC is not responsible for the content of Internet sites.)

American Cancer Society

American Heart Association

Centers for Disease Control and Prevention (CDC)

Leukemia & Lymphoma Society

National Institutes of Health (NIH)

National Women's Health Information Center

US Department of Heath and Human Services

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Substance in Tomatoes Aids in Heart Disease Prevention

Just one serving a day of tomato-based foods such as pizza or tomato sauce could lower your risk for heart disease by as much as 30 percent, contends a new Harvard University study.

"The results are pretty enticing," says study author Dr. Howard Sesso, of the Harvard School of Public Health and Brigham and Women's Hospital in Boston. "They're encouraging enough for us to do more studies."

The findings appear in the Journal of Nutrition.

Dr. Sesso and his colleagues reviewed the diets of approximately 40,000 women from the ongoing Women's Health Study, which was begun 11 years ago to follow women who, at the time, were free from cancer and cardiovascular disease.

The researchers controlled for factors such as age, family history, smoking status, and other health indicators.

They found that women who consumed seven or more servings of tomato-based foods a week - including tomato juice, tomatoes, tomato sauce, or pizza - had a nearly 30 percent reduction in risk for cardiovascular disease compared with women who ate less than one and one-half servings a week.

The study was sparked by research that has shown a connection between an increase in the diet of the antioxidant lycopene and a reduction in risk for prostate cancer, Dr. Sesso says.

Since tomatoes are a rich source of lycopene, he and his colleagues were interested to learn if the same antioxidant qualities, when eaten in tomatoes, might also lower heart disease risk.

Interestingly, however, when the researchers tabulated the result, the lycopene intake itself was not significantly associated with reduced heart disease risk.

However, when they looked at food intake, as measured by self-reported servings, there was a clear cardiovascular benefit for those who consumed the tomato-based products on a regular basis.

"Our study suggests preliminary evidence that consuming a number of servings of tomato-based foods per week may lower the risk of cardiovascular disease," Dr. Sesso says.

Connie Diekman, director of university nutrition for Washington University in St. Louis, finds the study promising, both because the large number of women surveyed make the results significant and because the findings concur with other work on the topic.

"The results may still be inconclusive, but the indication that lycopene/tomatoes may aid in the prevention of disease continues to evolve," Ms. Diekman says. "I would encourage people to take these results and add them to the growing list of studies that point to the benefits of more fruits, vegetables, and whole grains."

Dr. Sesso points out that those people who showed the benefit from eating the tomato foods might just have an overall healthier diet than those who had fewer servings of tomatoes.

"It could be the diet itself, one that includes more fruits and vegetables," he says. "Those people would have a better cardiovascular profile."

"It's hard to be specific," Dr. Sesso says of the findings, "but there's a potential that regular servings of tomatoes can have a dramatic effect on cardiovascular risk."

Always consult your physician for more information.