Better leukemia survival.

Once invariably fatal, acute myeloid leukemia (AML) still kills most of its victims. But a study involving 1,088 patients treated at medical centers across the country now indicates that more aggressive chemotherapy may help this cancer's younger sufferers.

At the most effective dose studied, the new regimen is often so toxic that many patients, especially those over age 60, cannot tolerate it. But for those who can, rates of long-term remission appear comparable to those seen in patients receiving bone-marrow transplants from a marrow-matched sibling. That's currently the most promising treatment option, but it's not available to many.

In AML, which hits 6,400 people in the United States each year, blast cells -- produced in the bone marrow -- don't mature as they should into granulocytes, a type of infection-fighting white blood cell. Oncologists usually use chemotherapy to kill those blast cells, starting with some combination of cytarabine and at least one other drug. The 65 percent of treated patients who then go into remission, or show no signs of disease, typically begin a period of maintenance therapy. At this stage, researchers tried increasing the dosage.

In the new study, they gave about one-third of 596 patients who entered remission daily doses of 100 milligrams of cytarabine per square meter of body surface area for 5 days. The researchers gave the other volunteers either 4 or 36 times as much drug. Patients received four courses of their regimen, each at least a month apart.

The older the individual and the higher the dose, the more likely a patient was to suffer seizures and other forms of cytarabine's potentially irreversible neurotoxicity, report Robert J. Mayer of Harvard Medical School in Boston and his coworkers in the Oct. 6 NEW ENGLAND JOURNAL OF MEDICINE. But among those age 60 and under who tolerated the drug, the probability that an individual would survive diseasefree for at least 4 years climbed from 24 percent among those on the 100-mg dose to 29 percent in the 400-mg group and to 44 percent in the megadose group.