In unrelated donor transplantation, research has shown that using younger donors can improve transplant outcomes. But it’s unknown whether young unrelated donors can lead to improved survival compared to older sibling donors. New research presented at the BMT Tandem Meetings, however, has shown that younger donor age correlates with higher CD-8 T cell counts, and that more CD-8 T cells lead to significantly better HCT outcomes.
The researchers prospectively studied 200 patients undergoing reduced-intensity conditioning peripheral blood stem cell (PBSC) transplantation between 2007 and 2014 at the University of Pennsylvania. Median age of the patients was 62 years (range, 21-76), and were transplanted using sibling (42.5%) or unrelated (57.5%) donors.
Researchers categorized PBSC grafts with ≥0.72 x 108/kg CD8 cells as high CD8 grafts. Patients receiving a high CD8 graft had significantly improved overall survival (OS) (adjusted hazard ratio [HR]: 0.53, p=0.007). One-year OS was 77.1% vs. 50.2% using high and low CD8 grafts, respectively, (p=0.0002). A high CD8 graft was also significantly associated with a decreased risk of relapse: adjusted HR: 0.43; p=0.009. A graft analysis found that younger donors tended to have higher CD8 cell doses (p<0.001) with 45% of donors <40 providing high CD8 doses while all donors over age 60 provided low CD8 grafts.
In an oral presentation of the research, lead author Dr. Ran Reshef reported that a high CD8 cell dose could be predicted during donor screening: Donors whose grafts contained a higher CD8 cell dose were significantly correlated with a higher percentage of CD8 cells (r=0.69, p=0.0004) and lower CD4/8 ratio (r=-0.55, p=0.007) in a screening blood sample.
Dr. Reshef concluded that using young unrelated donors with high CD8 grafts lead to better survival compared to older sibling donors and that donor selection based on predicted CD8 cell dose should be considered in prospective trials of reduced-intensity HCT.