Researchers from the University of Pennsylvania’s Abramson Cancer Center (ACC) have recently released study findings suggesting that screening for donor T cell characteristics will improve donor selection and lead to more successful transplants in an older population. The study, entitled, “High Graft CD8 Cell Dose Predicts Improved Survival and Enables Better Donor Selection in Allogeneic Stem-Cell Transplantation With Reduced-Intensity Conditioning,” was published in the latest edition of the Journal of Clinical Oncology.
Background Terminology:
- CD8+ T cells: cytotoxic T cells are very important for immune defense against pathogens such as viruses and bacteria, as well as, for tumor surveillance. When a CD8+ T cell recognizes a pathogen or other foreign substance it becomes activated, killing infected or malignant cells.
- Allogeneic stem cell transplantation: involves transferring stem cells from a healthy person (the donor) to a patient after they have undergone high-intensity chemotherapy or radiation and is done in an effort to cure patients who:
- Are at a high risk of relapse
- Don’t respond fully to treatment
- Relapse after prior successful treatment
Stem cell transplants are used to treat lymphoma patients who are in remission or who have had a relapse during or after treatment. Matching donors and patients is a complex endeavor and currently, matched siblings are preferred over unrelated donors. Although, even when donors and patients are matched siblings, there are still complications that arise with patient survival rates post-transplant still not meeting clinical expectations. To reduce complications and increase survival rates, physicians and scientists are actively seeking better methods to match patients and donors.
In this study, researchers evaluated the associations between the number of T cells present in the transplant graft and survival outcomes in 200 ACC patients with blood cancers such as, acute myeloid leukemia, myelodysplastic syndrome, and non-Hodgkin lymphoma.
The team observed that increased numbers of CD8 T cells in the stem-cell graft had a positive impact on survival. Furthermore, these increased CD8 T cell counts were much more common among young donors.
Other important findings showed that:
- The four-year overall survival rates were 59 percent for younger, unrelated donor grafts with high CD8 T cell counts, 18 percent for younger, unrelated donor grafts with low CD8 T cell counts, and 33 percent for older, HLA-matched sibling donor grafts.
- The CD8 T cell content of the graft could be predicted by measuring the proportion of CD8 T cells in a blood test from potential stem cell donors, providing a simple way to screen for the best donor even before the stem cell graft was collected.
These findings give supportive evidence suggesting that it would be more beneficial to use a younger unrelated donor graft with high CD8 cells instead of an older sibling donor.
In a University press release on the study’s findings, Dr. Ran Reshef, MD, assistant professor, Division of Hematology/Oncology, Hematologic Malignancies Research Program, ACC, and lead study co-author, stated, “Developing better tools to identify ideal donors is an exciting prospect—and fundamental to improving transplant outcomes. There may be suitable donors out there who are overlooked because they are considered a poorer match by today’s donor selection algorithms. Refining the screening method could greatly increase the chances of finding the most appropriate donor, one that will induce the most potent graft-vs-tumor response.”
Dr. Reshef, continued, “This is a method deserving additional investigation, which could refine the standardized matching system used by registries, such as Be the Match and others, and ultimately optimize the donor pool for older patients undergoing these transplants.”
