Dr. Cooke

For some of his patients, Dr. Kenneth Cooke saved their life not once, but twice.

Dr. Cooke, who specializes in bone marrow transplantation at U- M Comprehensive Cancer Center, provides life-saving treatment for the sickest cancer patients. But his time is also spent researching and developing ways to make this treatment safer.

“Although bone marrow transplantation represents the only chance for cure for many of our patients, several of the complications that arise following BMT can be life-threatening,” said Dr. Cooke. “Understanding how these complications develop and, ultimately, how they might be more effectively treated is one of my passions.”

The primary complication that occurs when patients receive a BMT from a related or unrelated volunteer donor is called graft-vs.-host disease, or GVHD. Much like a patient receiving a heart or kidney transplant must worry about the body rejecting the new organ, in bone marrow transplants, the specialized white blood cells from the donor bone marrow can reject the patient. GVHD can occur even when the donor and host are genetically matched and typically affects the skin, liver, intestinal tract and lungs. These organs serve as barrier, filtering toxins that have been ingested or that remain outside the patient.

When the lungs are attacked after BMT, they become inflamed and filled with fluid, preventing normal oxygen exchange. The patient becomes short of breath and may ultimately require a mechanical ventilator to breathe. When there is no evidence of infection in the lungs, this form of pneumonia is called “idiopathic pneumonia syndrome” (IPS). IPS is frequently fatal – 70 percent to 80 percent of patients who develop IPS do not survive, and the average time from diagnosis to death is only 14 days.

Working toward a solution is a lengthy process. “First we developed mouse BMT models of human disease to understand IPS and obtain insights on the precise mechanisms of tissue injury,” explained Dr. Cooke. “That's where we made the connection between a protein called tumor necrosis factor (TNF) and the lung inflammation that is engendered during the development of IPS.”

Dr. Cooke's team worked in the laboratory to identify key factors in the development of IPS. From there, they found Enbrel, a medication that is FDA approved to treat certain forms of arthritis and psoriasis, neutralizes the effects of TNF. These lab studies then moved on to clinical trials to determine whether it would be safe and effective in patients.

“Early phase clinical trials can not only help us develop treatments for future patients but, when we are lucky, also provide life-saving, cutting-edge solutions for patients right now,” Dr. Cooke said.

One such success story is a teen named Rachel.

When Rachel was a child, she had a cancer called neuroblastoma and received a bone marrow transplant using her own cells. Although the transplant was a success and Rachel was cured of her neuroblastoma, many years later, she developed a blood disorder that was caused by the intense chemotherapy she had received. The only curative option for this blood disorder was a second bone marrow transplant. This time, Rachel would need cells from an unrelated volunteer donor, which put her at much higher risk for complications. Shortly after receiving her second transplant, Rachel developed IPS in her lungs. She was near death when her parents agreed to enroll her in Dr. Cooke's clinical trial.

“The results were phenomenal,” he said. “Rachel went from requiring 100 percent oxygen and a mechanical ventilator to breathing comfortably on her own in 96 hours.”

Now, Dr. Cooke and his team are expanding their clinical studies and sharing these incredible results with medical professionals around the world.

“That's what is most exciting about being at a medical center where laboratory research and patient care come together around a team of talented and dedicated bone marrow transplant physicians and nurses, and incredibly courageous patients and families. It's exciting to be on the cutting edge of medical research – to be in a position to raise the standard of care for our patients.”