Source: Jeffrey Norris, UCSF Today
December 7, 2007

Leukemia Survival and Pharmacogenetics

There's a new way to personalize drug therapy. It's pharmacogenetics -- using information on genetic differences to tailor treatment.

Deanna Kroetz, PhD, of UCSF's School of Pharmacy is exploring pharmacogenetics in the most common and deadly form of adult leukemia. The cancer is called acute myelogenous leukemia (AML). It stems from immature white blood cells in the bone marrow. AML afflicts 11,000 mostly elderly adults each year.

In cancer, drug effectiveness sometimes depends on normal variations among certain genes we inherit. Scientists call these variations polymorphisms. Likewise, differences among the genetic mutations and other abnormalities that arise within individual cancers also can affect drug responses.

Pharmacogenetics in the Most Deadly Leukemia
Time is of the essence in treating cancers. When oncologists diagnose AML, they often start the patient on chemotherapy the same day. Time lost to trial and error with chemotherapy that is ineffective or that causes unbearable side effects can increase the likelihood that an evasive cancer will eventually grow uncontrollably.

Remarkably, roughly eight out of 10 patients under age 60 who develop AML enter complete remission after an initial course of chemotherapy. This means that treatment leaves no sign of leukemia cells in the blood, and that the bone marrow again makes blood and immune cells in normal amounts.

But just as remarkably, in about half of these patients who initially fare so well, cancer returns, usually within a year. Older patients fare even worse. A new population of leukemia cells grows back from ancestors that survived earlier treatment while remaining undetected. When the leukemia returns, it is resistant to the first-used drug, so oncologists must choose an alternative.

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