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Drug duo: New hope in cancer fight

BY ALAN BAVLEY
Knight Ridder Newspapers

Dec. 18, 2005 - KANSAS CITY, Mo. - Patty Holtz has been battling her cancer for 15 years. Now she's confident that a one-two punch has knocked it out for good. An experimental two-drug combination has made it possible for Holtz to receive a successful transplant of her own stem cells after a previous attempt had failed.

"This gives me hope and lets me go on with my life," said Holtz, 56. "The prognosis just wasn't very good if I didn't have this transplant."
The drug combination could be a lifesaver for thousands of patients like Holtz who haven't been able to muster enough of their own stem cells for a transplant, said her doctor, Joseph McGuirk.

"This is incredible; this is spectacular. We don't often get this kind of benefit from cancer drugs," McGuirk said. "Patients who had nowhere else to turn, patients who were going to die, can be cured."
Last week, McGuirk presented results on 70 patients at the annual meeting of the American Society of Hematology in Atlanta. The patients were treated by McGuirk and his colleague, Sunil Abhyankar, and by other doctors in other parts of the country.

All the patients had failed one or more attempts at transplantation with conventional therapy. But with the drug combination, 42 patients - more than half - were able to produce enough stem cells. Thirty-eight of the patients received successful transplants.

"That's pretty exciting news," said Deborah Banker, a cancer research biologist and vice president of the Leukemia & Lymphoma Society.
"Obviously, this is an early study and more data will be needed," Banker said, "but I think a lot of people have hope that this will move into the mainstream. People recognize this as an important problem - getting enough stem cells is absolutely critical to expanding the use of stem-cell transplants."

The stem cells transplanted in these patients are not stem cells taken from human embryos. Rather, they are from the patients' bone marrow.
About 45,000 cancer patients a year in the United States and Europe undergo these procedures, called autologous stem-cell transplants.
The patients that McGuirk reported on had cancers of the lymph nodes or bone marrow, diseases such as multiple myeloma, acute myelogenous leukemia or Hodgkin's disease.

About half the patients with these cancers can be cured with standard chemotherapy or chemotherapy combined with radiation. But for the rest, the cancers return more determined than before. Cancer cells become resistant to the highly toxic chemotherapy drugs. They learn to repair the DNA damage the therapy causes, or they develop the ability to simply pump the drugs out.

As higher doses of chemotherapy are needed to eliminate the cancer, the stem cells that make blood and vital components of the immune system also can be destroyed. "All too often it's a balancing act (between) killing the cancer and killing the patient," McGuirk said.

The alternative is to collect millions of stem cells from the patient and store them, frozen, before delivering high doses of chemotherapy. Once the cancer is eliminated, the stem cells can be returned intravenously, like a blood transfusion, to the patient. The cells migrate from the bloodstream back to the bone marrow and start working again.

Doctors have routinely given transplant patients a drug called Neupogen to coax the bone marrow to produce more stem cells. The cells are then filtered out of the patient's blood.

But about a fourth of patients cannot muster enough stem cells to make a transplant possible. Often, their only alternative is the diminishing returns of more chemotherapy.

"It's a life-and-death matter for these patients," McGuirk said.
The experimental therapy McGuirk and other doctors are trying combines Neupogen with another drug, AMD3100, that dislodges stem cells from their home in the bone marrow.

The researchers found that with the addition of AMD3100, considerably more stem cells entered the bloodstream. That made it possible in most cases for doctors to collect enough of the cells for a transplant.
Patty Holtz developed non-Hodgkin's lymphoma, a cancer of the lymph nodes, 15 years ago. Chemotherapy kept it in check for about eight years. Then her cancer returned. A second round of chemotherapy and radiation put her in remission.

Late last year her cancer came back in a more aggressive form. A stem-cell transplant was her only chance at long-term recovery.
"Without this it was a matter of going through the chemos again, and I knew the remissions were getting shorter," Holtz said.
During Holtz's first try at a transplant, doctors collected only negligible numbers of stem cells.

"It was disappointing," she said. "But a lot of people who had a lot of chemos don't produce a lot of stem cells."
After receiving the two-drug therapy, Holtz received a successful transplant in late May.

Now that researchers know AMD3100 works well in patients who previously failed transplant attempts, the next step is to see whether the drug improves the odds of new transplant patients as well. Clinical trials are under way. McGuirk is participating. "Why wait? Why not do this upfront for the patient to avoid the heartbreak, the emotional trauma when a transplant fails," he said.

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