Impact of Gender: Female Matched Related Donor Versus Male Matched Unrelated Donor on Peripheral Blood Allogeneic Stem Cell Transplant for Male Recipients

Abstract

expansion was reliably achieved when artificial APCs were used. In contrast, when donor PBMCs (without artificial APCs) were used as the source of APCs, 10-100 fold fewer Tregs were obtained. Regardless of protocol, pTregs successfully prevented the proliferation of bead (CD2CD3CD28) stimulated self PBMCs with up to 50% suppression at a 1:32 ratio of Tregs:PBMCs. Contamination of CD8+ T cells was observed despite our efforts to gate out CD8 cells during sorting. Resorting of the Treg cultures early (day 14-21 post isolation) successfully eliminated the CD8s. Resorting inherently caused a significant loss of Tregs, leading to a longer culture period. Because Treg burnout was of concern, we assessed the function and phenotype of cells maintained in cultures >50 days and observed that Tregs with early high FoxP3 expression maintained function and phenotype. Finally, demonstration of fitness of cryopreserved pTregs is necessary for clinical application. Our preliminary studies show that Tregs can be re-cultured and re-expanded without loss of suppression or phenotype. In summary, we have successfully established several protocols for Treg expansion in the Cynomolgus macaque that can be used in pre-clinical studies of transplant tolerance induction.

Graft-versus-host disease in recipients of male unrelated donor compared with parous female sibling donor transplants

“…Although some prior studies in URDs have found no association between parity and OS, 24 others have demonstrated poorer OS (and higher TRM) in male recipients of female grafts, 31 and yet other analyses have shown improved OS. 32 It is difficult to reconcile the marked differences in survival outcomes in the many studies that have evaluated donor sex or parity, but our large study suggests that if parity is a risk factor for GVHD or other poor outcomes, it is not as significant as the effects of receiving a graft from a URD. Like most transplant analyses, we confirmed that older patient age, poorer patient performance status, advanced disease, and earlier year of transplant were associated with poorer OS.…”