TY - JOUR
T1 - Early CD3 Peripheral Blood Chimerism Predicts the Long-Term Engrafting Unit Following Myeloablative Double-Cord Blood Transplantation
AU - Newell, Laura F.
AU - Milano, Filippo
AU - Nicoud, Ian B.
AU - Pereira, Stacey
AU - Gooley, Ted A.
AU - Heimfeld, Shelly
AU - Delaney, Colleen
N1 - Funding Information:
The authors are grateful to the patients and families who consented to the use of clinical research results and biologic specimens in these trials. The authors thank Denise Ziegler, Ivy Riffkin, MaryJoy Lopez, and Adrienne Papermaster for their assistance in the preparation of this manuscript. This work was supported by the National Institutes of Health (Grants T32 HL007093 , L.F.N.; K23 HL077446 , C.D.; ALC CA18029 , S.H. and T.A.G.; DK56465 , S.H.; CA15704 ) and by medac GmbH. C.D. is a Damon Runyon Clinical Investigator supported in part by the Damon Runyon Cancer Research Foundation (CI# 35-07). F.M. is a recipient of a Research Fellowship from the Fondazione Internazionale di Ricerca in Medicina Sperimentale, Torino, Italy sponsored by “Provincia di Benevento.”
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Double-cord blood transplantation
KW - Long-term engrafting
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U2 - 10.1016/j.bbmt.2012.01.014
DO - 10.1016/j.bbmt.2012.01.014
M3 - Article
C2 - 22326302
AN - SCOPUS:84863992615
SN - 1083-8791
VL - 18
SP - 1243
EP - 1249
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 8
ER -