2009 Annual Report: Spotlight on Leukemia

Spotlight on Leukemia

On June 18, 2009 the CIRM governing board heard a Spotlight on Leukemia featuring a clinician and patients speaking about their hope for stem cell research. These are their stories.

Theresa Blanda
Orange, CA

In October 2008 Theresa Blanda was at a turning point. Already she ached. A tumor grew on her knee, forcing her to use a walker. Now laboratory tests showed the blood disorder she had fought for five years was turning into leukemia

Blanda had been diagnosed with polycythemia vera — an overproduction of red blood cells. But in 10 to 15 percent of all cases, the disease toggles into an overproduction of white cells and eventually acute leukemia. Blanda’s body produced as many as 95,000 white cells per cubic millimeter of blood, far above the normal 8,000 or so.

“I was headed down the leukemic path,” she said.

Her only hope was a bone marrow transplant, but there was no suitable donor. Then she learned of an experimental trial at the University of California, San Diego, targeting the stem cells that cause cancer. In October, she enrolled in the trial.

Bone marrow transplants are risky and expensive—the procedure costs roughly $250,000.

“Within two months I went from using a walker, to a cane, to walking on my own,” she said. Her white blood cell count dropped to normal. Today she's back at work and off the bone marrow transplant list.

“They’re hoping that treating this at the stem cell level means this can be treated like a chronic disease, like diabetes,” Blanda said. “Will it keep working for me? I hope so.”

CURING LEUKEMIA

A type of stem cell appears to be the Achilles’ heel in some forms of blood cancer including leukemia. Since 1937, some researchers have hypothesized that cancers arise from certain of the body’s stem cells, the cells primed to make a variety of other cell types.

If true, cancer may be most vulnerable there, at its source. The problem was, “For a long time the tools didn’t exist to really examine this hypothesis,” said Dr. Catriona Jamieson, M.D., Ph.D., an assistant professor at the University of California, San Diego.

But a recently completed phase 1 trial for a drug created by a San Diego-based company, TargeGen Inc., and investigated in Jamieson’s lab, demonstrates that at least in the case of polycythemia vera, this focus on the stem cells, where the body first stumbled into disease, holds promise.

Phase 1 studies test a treatment’s safety, not it’s effectiveness. The question of whether the drug works isn’t addressed until a Phase II trial, after it is proven to be safe at a range of doses. So Jamieson, the director of the stem cell research program at the Moores UCSD Cancer Center, wasn’t expecting symptom improvement when the drug entered these early trials in patients with advanced disease. She knew it worked in tissue culture. Her laboratory had proved its efficacy in animal studies. But its success in humans wouldn’t be tested unless phase 1 ended successfully.

But to Jamieson’s surprise, the phase 1 trial improved the health of all 59 trial patients, many dramatically. Myelofibrosis, a life-threatening scarring of the bone marrow, leaves its victims weak and tired, with spleens uncomfortably enlarged as the disease advances toward leukemia. In the safety study, the spleens of all patients reduced in size by half or more. In half of the patients, spleen size returned to normal. Abnormal production of white blood cells ceased in all patients.

“It’s exciting and kind of unexpected,” Jamieson said. “This was supposed to be a safety trial.”

The drug inhibited the stem cell’s initial error, the mutation of a gene called JAK-2, named for Janus kinase 2. The gene mutates in 97 percent of all cases of polycythemia vera, in which the body makes too many red cells, half of all instances of thrombocytosis, in which there are too many platelets, and half of all cases of myelofibrosis. In the trial, half of all patients saw levels of mutant protein drop markedly.

“I thought it would be too little too late,” Jamieson said. “I didn’t think the results would be so good.”