Seattle Children’s researchers are working on new ways to do transplants so children can avoid severe or long-term graft-versus-host disease (GVHD). GVHD happens after a stem cell transplant if the new cells attack the child’s body instead of rebuilding the immune system.
Dr. Marie Bleakley has identified a subset of T cells from donor stem cells that are most likely to attack a patient’s normal cells and cause GVHD. Her lab team developed a way to remove the troublesome subset of T cells from the donor cells before transplant but keep helpful T cells. This is called “naive T-cell depletion.” The helpful T cells fight infections that often happen after transplants. The T cells also protect the child from leukemia coming back.
In the first phase 2 clinical trial using the new naive T-cell depletion method, fewer patients had GVHD than usually happens after transplantation. Patients also needed less treatment with drugs that suppress their immune systems after transplant. This means they could get immunotherapy sooner after transplant to prevent cancer from returning. Bleakley continues to study the new method.
Dr. Leslie Kean studies how the body integrates immune cells that are transplanted from another person. She is studying ways to control T cells from donors so they don’t attack the cells of transplant patients. The insights from her lab studies are laying the foundation for the next generation of therapies.
Previously, Kean developed an innovative animal model for GVHD and discovered that a drug for rheumatoid arthritis dramatically improves how animal models tolerate transplants. This drug is now being tested in a Food and Drug Administration (FDA)–funded trial that Kean runs. It is the largest such trial for children in the country.