ASH 2025 | Effect of graft cellular content on outcomes in HLA-mismatched alloSCT with PTCy as GvHD prophylaxis

We know that donor age can impact outcomes after allogeneic transplants. However, the biological reasons behind it are still unclear, especially in the PTCy era where immune reconstitution, CRS, and GvHD follow different patterns. So we asked whether donor age can impact graft contents and whether it translates into differences in terms of immune reconstitution and clinical outcomes. We conducted a retrospective study at Dana-Farber Cancer Institute, including 340 patients who received allogeneic transplants with a PTCy-based GvHD prophylaxis. So what are the findings? 

First, donor age mainly impacts the CD4-CD8 balance. Younger donors provide grafts with higher numbers of CD8 and lower CD4 counts. However, age of the donor did not impact CD34, TNC, B-cell, and NK-cell counts. Second, we see that the incidence of CRS is correlated to the CD4 counts in the graft, and that experiencing a CRS has a strong impact on immune recovery. Actually, patients who experience CRS have an earlier engraftment assessed by T-cell chimerism. They have a memory-skewed CD4/CD8 phenotype, and they also have lower Treg recovery. Third, we see that the graft content has different impacts in terms of immune reconstitution. So if the graft has a higher CD4 count, there is an earlier recovery of naive CD4 cells. However, CD8 expansion seems mainly driven by the occurrence of CRS. Finally, in patients who have higher CD4 and who experience CRS, there is a higher risk of acute and chronic GVHD. So overall, donor age mainly impacts the CD4-CD8 balance in the graft, but the quantitative cell count cannot solely explain all the clinical outcomes. CRS seems to have a large role in immune reconstitution and may also play a role in the development of GVHD.

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