SEATTLE -- When Jan Harding was diagnosed with acute myeloid leukemia (AML) she was ready for a fight.
“I thought, ‘Whatever I have to do next, bring it on because we have to get through this,’” Harding said.
So when standard therapies failed to conquer the 59-year-old Tacoma woman’s cancer, Harding joined an experimental study at the Fred Hutchinson Cancer Research Center. That therapy saved her life, and researchers now believe it could help other cancer patients who have run out of treatment options.
Harding went through five month-long rounds of chemotherapy in 2009, but her leukemia continued to spread. Doctors advised Harding that her best chance of survival would be a stem cell transplant.
Unfortunately relapse after a stem cell transplant is the leading cause of death for patients with high-risk leukemias. Harding’s doctors predicted she had a 20 percent chance of surviving three years.
“The thought that I might not get to see my granddaughter grow up was heart-wrenching,” Harding said.
To improve her odds, Harding decided to try a new experimental treatment.
Dr. Phillip Greenberg, head of the immunology program at Fred Hutch, initiated a trial 11 years ago using the immune system to treat patients with aggressive leukemias including AML, acute lymphoid leukemia and myelodysplastic syndromes . His hope was to decrease the number of patients who relapse after a bone marrow or stem cell transplant. Greenberg believed he could offer a therapy that would better target cancer cells and do less damage to healthy tissue.
With funding from the National Cancer Institute and Leukemia & Lymphoma Society, Greenberg recruited eleven leukemia patients who had been through standard bone marrow or stem cell transplants. These patients had either relapsed or were at high risk of relapsing.
Greenberg and his colleagues were attempting to use donated T-Cells – a type of white blood cell that fights infections in the body – to kill leukemia cells. Researchers trained the T-Cells cells to recognize a specific protein – Wilm’s Tumor Antigen 1 (WT1) – found in leukemia cells. The T-Cells were able to tell the difference between leukemia cells and normal cells, so the trial participants were less likely to develop graft-versus-host disease. Because the therapy was less risky to healthy tissue, researchers were able to infuse approximately 10 billion cells into patients – many more than in a standard transplant.
Early in this study, patients infused with the programmed T-Cells saw desired results; the T-Cells were killing the leukemia cells. Unfortunately, the T-Cells only survived in patients for a maximum of 14 days, and these patients eventually relapsed.
However, researchers modified the protocol for a second group of patients. Before infusing these T-Cells, researchers exposed them to a drug – interleukin 21 (IL21) – designed to keep them alive longer and allow them to kill more leukemia cells.
Harding was one of four patients in this second group. Five months after she had a standard stem cell transplant with donated cells from her sister, researchers infused Harding with programmed T-Cells – also from her sister. The cells survived in Harding for 430 days and are believed to have kept her cancer from relapsing.
“It was amazing,” Harding said. “I’m just in awe of what they’re able to do.”
Three years later, Harding is still cancer free. She now has two more grandchildren to fight for.
“I feel enormous gratitude,” she said.
All four patients who received the T-Cells exposed to IL21 survived at least 30 months after transplant without suffering graft-versus-host disease or requiring additional leukemia treatment. One of the four has died, though he survived much longer than the three months doctors had predicted he would live with a standard transplant. The other three, including Harding, are alive today and cancer free.
Researchers at Fred Hutch say this study proves immunotherapy can improve transplant outcomes, and expect it could be used to treat other types of cancer as well.
The study has already inspired new research. Dr. Aude Chapuis, lead author on the study and a research associate in Fred Hutch’s Immunology program, is now directing a new trial now that will aim to use donor cells that can recognize leukemia cells even better and will treat patients before they have a transplant.
“Someone contemplating transplant at this point is at very high risk of the disease coming back,” Chapuis said. “At Fred Hutch patients can be enrolled in a trial that attempts to keep their leukemia at bay after a transplant.”