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New Drug Treatments Offer Hope to Leukemia Patients

'Targeted' therapies prevent cells from reproducing uncontrollably

TUESDAY, Sept. 28, 2004 (HealthDayNews) -- Scientists call them "molecularly targeted" drugs, and they represent a remarkable gain in the war against blood cancers.

Leukemia, lymphoma and myeloma are some of the rarest yet most deadly forms of cancer. They account for only 2 percent to 3 percent of all cancers, but cause 10 percent of all cancer deaths, said Alan Kinniburgh, vice president of research for the Leukemia & Lymphoma Society.

These so-called "liquid cancers" cannot be surgically removed and up until recently have been treated with radiation and chemotherapy.

But promising new therapies all involve "molecularly targeted" drugs that disrupt the spread of cancer by honing in on specific mechanical processes that cancer cells to grow.

These breakthrough treatments merit attention in September, which is Leukemia & Lymphoma Awareness Month.

Kinniburgh foresees a day when these new drugs will work together to halt blood cancers, "all hitting the same target, but hitting the target in different ways so the target can't escape being killed."

An estimated 106,000 Americans were diagnosed with leukemia, lymphoma or myeloma last year, according to estimates by the National Cancer Institute. Another 57,500 people died from one of the diseases.

The diseases each begin with one damaged cell that turns cancerous, explained Hildy Dillon, vice president of patient services for the Leukemia & Lymphoma Society.

"They are usually the result of an acquired genetic injury to the DNA of a single cell, which then becomes malignant and starts to reproduce," Dillon said.

The blood cancers interfere with the production of healthy blood cells, Dillon said.

If red blood cells are affected, the person initially suffers from anemia and fatigue. If white blood cells are stricken, the patient initially suffers a high risk of infection. And since the cancers affect blood's ability to clot, patients also suffer unexplained bruises.

If left untreated -- or detected too late -- the blood cancers will kill.

The biggest recent leukemia breakthrough involved the drug Gleevec, which inhibits an enzyme that pushes cells to reproduce uncontrollably. The drug, which gained U.S. Food and Drug Administration approval in 2001, has been stunningly successful in treating people with chronic myeloid leukemia, often returning patients' blood cell counts to near normal within three or four weeks.

Building on the success of Gleevec are three other new therapies that hold promise, Kinniburgh said.

The first involves clofarabine, a drug that disrupts DNA replication in cancer cells. The drug has been found in clinical trials to put about one-quarter of acute lymphoblastic leukemia (ALL) patients and acute myeloid leukemia (AML) patients into remission when other treatments have failed, Kinniburgh said.

"That provides extra time for a patient to undergo a bone marrow or stem-cell transplant," he said. "That's going to save children's lives." The drug is awaiting FDA approval.

Another set of drugs undergoing clinical trials are FLT-3 inhibitors, which can disrupt cellular communications that spur cancer growth. Again, about one-quarter of patients with acute myeloid leukemia respond to the drugs, but those who do respond show an 80 percent to 90 percent reduction of cancer cells in the blood, Kinniburgh said.

The third drug, which Kinniburgh calls "Son of Gleevec," is an ABL-kinase inhibitor that targets cancer cell mutations that escape treatment with Gleevec. The drug, BMS-354825, is being tested in patients with chronic myelogenous leukemia whose bodies are resistant to Gleevec.

Doctors generally don't know what causes blood cancers. Benzene, smoking, radiation and the Epstein-Barr virus have all been linked to the diseases, but most of the time physicians have no idea why a specific person has contracted a blood cancer.

"Most often, there really isn't a known cause," Dillon said. "These are not diseases that can be prevented."

There also are multiple types of each of the diseases, which can make it tough for doctors to know how to proceed, Dillon said.

"The challenge is to determine the type of blood cancer a person has because the treatments are designed very specifically," she said. "They're beginning to be able to really target the specific mechanics of each of these different types of cancer.

Leukemia involves cancer of the bone marrow and blood cells, and strikes about 30,600 Americans each year. Another 21,900 die from the disease annually.

Lymphomas are malignancies of the lymphocites, a type of white blood cell. This is the most common blood cancer, afflicting 61,000 people a year and killing 24,700.

Myeloma affects the plasma cells, or white blood cells found primarily in the bone marrow. About 14,600 people are diagnosed with this disease each year, and another 10,900 die.

Leukemia has a five-year survival rate of 44 percent. Lymphoma has a 52 percent survival rate, and myeloma has a 28 percent survival rate.

Kinniburgh said all of the new drug treatments could ultimately be used in concert to specifically target different blood cancers, no matter how rare or obscure.

"With several of these agents hitting each other's cross-resistance, it's certainly very likely we may be able to treat all patients without radiation or chemotherapy," he said. "At some point the goal and the dream would be the drugs could be withdrawn from the patients and they would go on in remission."

More information

To learn more about blood cancers, visit the Leukemia & Lymphoma Society.

SOURCES: Alan Kinniburgh, vice president, research, Leukemia & Lymphoma Society, White Plains, N.Y.; Hildy Dillon, vice president, patient services, Leukemia & Lymphoma Society
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