Extending Targeted Immune Depletion to Unrelated Cord Blood Transplantation
Name of the Trial
Pilot Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Matched Unrelated Double Cord Blood Transplant for the Treatment of Leukemias, Lymphomas, and Pre-Malignant Blood Disorders(NCI-09-C-0210). See the protocol summary.
Dr. Michael Bishop, NCI Center for Cancer Research
Why This Trial Is Important
Using umbilical cord blood from unrelated donors for allogeneic stem cell transplantation may help save the lives of people with blood or immune system cancers. Umbilical cord blood is rich in blood-forming stem cells that can be used to reconstitute the immune systems of patients whose immunity has been reduced by disease or pre-transplantation conditioning therapy.
In allogeneic stem cell transplantation, patients undergo a pre-transplantation conditioning regimen of chemotherapy or radiation therapy to kill cancer cells and suppress the immune system. Then, healthy donor stem cells are infused into the patient to rebuild the immune system. If stem cells from a human leukocyte antigen (HLA)–matched related donor are not available, stem cells from an HLA-matched unrelated donor are used. As many as 40 percent of patients eligible for allogeneic stem cell transplantation have no HLA-matched related donor available.
However, rejection of the donor cells by the body and delayed reconstitution of the immune system are major problems with cord blood transplants. If the immune system does not reconstitute itself, or if it takes too long to do so, the recipient can experience severe or even life-threatening infections.
Researchers at NCI have developed a strategy called targeted immune depletion to help improve stem cell engraftment (incorporation into the body) and immune reconstitution in allogeneic transplantation by tailoring the extent of immune depletion to individual patients. For example, patients with strong immune systems may need more chemotherapy than patients with weak immune systems to deplete their immune cells.
In this pilot study, patients with leukemia, lymphoma, multiple myeloma, or certain premalignant blood disorders (such as myelodysplastic syndromes) will undergo targeted immune-depleting chemotherapy followed by transplantation of umbilical cord blood from two unrelated donors (double transplant). Doctors hope that using targeted immune depletion will limit the risks of chemotherapy-associated toxicity and transplant rejection while still allowing for a sufficient anticancer effect and rapid reconstitution of the immune system.
“Our aim is to extend the strategy of targeted immune depletion to umbilical cord blood transplants, with the goal of more rapid engraftment, leading to decreased treatment-related mortality and increased overall survival,” said Dr. Bishop. “If the strategy is successful, it could provide a more personalized approach to transplantation and enhance the possible donor pool, especially for subsets of patients for whom transplantation is often not available.”