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Battling Blood Cancers

New treatments may work better with fewer side effects

FRIDAY, Sept. 26, 2003 (HealthDayNews) -- Leukemia, lymphoma and myeloma: All three are blood cancers that can be fatal if left untreated, and yet none can be halted with surgery.

Until now, that has left chemotherapy as the first line of defense. But new molecularly targeted drugs are being hailed as precise and powerful weapons against cancers that are notoriously hard to treat.

"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.

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

To push beyond that 85 percent mark, researchers are pouring their energy into the development of these molecularly targeted drugs, which attack diseased cells directly and produce fewer side effects in the process.

To heighten awareness of these developments, the Leukemia & Lymphoma Society has also declared September as Leukemia, Lymphoma and Myeloma Awareness Month.

More than 100,000 Americans will be diagnosed with one of these three blood cancers in 2003. That's not counting hundreds of thousands more who are living with one of the diseases.

Lymphoma is the most common type of blood cancer, representing 57 percent of all cases. Leukemia makes up 30 percent of all cancers diagnosed in children under the age of 15.

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 chronic (which comes on 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, or white blood cells found primarily in the bone marrow, and it interferes with the body's immune system.

No one is sure what causes these cancers, although they are thought to arise when a single cell with a genetic flaw starts replicating uncontrollably.

While chemotherapy and other conventional treatments are still being used, the breakthroughs are happening with molecularly targeted drugs.

"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, an associate professor of oncology, pediatrics and cellular and molecular medicine at 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, 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, 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.

"It requires such intensive chemo that a lot of people consider patients over 60 or 65 can't be treated aggressively enough to have any chance," Small says. "We really need new types of therapies and it may well be that, when chemo is combined with some of the targeted therapies, we could see a big impact."

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," 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," Small says. "In AML, there are probably three or four or more altered genes."

There are other categories of therapy as well. 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," 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 and/or radiation," 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," 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."

More information

For more on the different blood cancers, visit the Leukemia & Lymphoma Society. The National Cancer Institute has information on leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma and on myeloma.

SOURCES: Alan Kinniburgh, Ph.D., vice president, research, Leukemia & Lymphoma Society, White Plains, N.Y.; Donald Small, M.D., Ph.D., associate professor, oncology, pediatrics and cellular and molecular medicine, Johns Hopkins University School of Medicine, Baltimore
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