Early CD3 peripheral blood chimerism predicts the long-term engrafting unit following myeloablative double-cord blood transplantation.
After double-cord blood transplantation, long-term hematopoietic dominance of a single-cord blood donor graft is established in the majority of patients; however, the mechanism behind this observation remains largely unknown. Beginning at day 7 posttransplantation, we prospectively measured weekly lineage-specific peripheral blood donor chimerisms in patients undergoing myeloablative double-cord blood transplantation to evaluate whether the degree of early donor contribution to specific lineage(s) would predict the long-term engrafting unit. Our results demonstrate that the donor unit with higher CD3 chimerism at day 7 became the dominant engrafting unit in 26 of 31 evaluable patients (P = .0002) and in 34 of 34 evaluable patients at day 14 (P < .0001). Similarly, higher donor unit CD33 chimerism was associated with dominant engraftment in 8 of 8 (day 7) and in 31 of 32 (day 14) evaluable patients. No statistically significant correlation between the dominant unit and order of infusion, infused total nucleated cells, CD34, or CD3 cell doses, unit viability, or HLA disparity was observed. The correlation of higher early posttransplantation donor CD3 peripheral blood chimerism with the dominant unit suggests a rapid immune-mediated response as a primary mechanism of action for long-term single-donor dominance. This finding may have clinical implications for early selection of the winning unit after double-cord blood transplantation and for novel cord blood manipulation strategies.
Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA 98109, USA.
Laura F
LF
Newell
Filippo
F
Milano
Ian B
IB
Nicoud
Stacey
S
Pereira
Ted A
TA
Gooley
Shelly
S
Heimfeld
Colleen
C
Delaney
D000293:Adolescent; D000328:Adult; D017252:CD3 Complex / Q000097:blood*; D002648:Child; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000097:blood / Q000276:immunology / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D018183:Transplantation Chimera; D016896:Treatment Outcome; D055815:Young Adult
D017252:CD3 Complex